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OBJECTIVE: The main importance of imaging breast cancer is to guide conservative surgeries. In this study, we evaluated the role of contrast-enhanced spectral mammogram (CESM) in correlation with three-dimensional (3D) breast ultrasound in characterizing the extension of the intramammary cancer in view of the: (i) the size of the main tumor, (ii) the multiplicity of the breast cancer, and (iii) the peri-tumoral stromal involvement (i.e. free or intraductal extension of the cancer). METHODS: The study is a prospective analysis that included 300 breast masses proved to be malignant. The masses were evaluated for their size, multiplicity and surrounding stromal involvement. Contrast-based mammography performed with low (22-33 kVp) and high (44-49 kVp) energy exposures that were taken after i.v. injection of contrast agent and followed by bilateral 3D breast ultrasound. Operative data were the gold standard reference. RESULTS: There was no significant difference between the sizes of the included cancers as measured by CESM and 3D ultrasound and that measured at the pathological analysis. CESM showed higher accuracy (32.7%, n = 98) than 3D ultrasound (24.7%, n = 74) in the size agreement within 5% range. CESM was the most accurate modality (94%, n = 282) in detecting tumor multiplicity, followed by traditional sonomammogram (88%, n = 264), then 3D breast ultrasound (84%, n = 252). Intraductal extension of the breast cancer was best evaluated by the 3D ultrasound with an accuracy value of 98% (n = 294) compared to only 60% (n = 180) by CESM. CONCLUSION: CESM is a recommended investigation in breast cancer to increase the accuracy of size measurement and the detection of multiple tumors. The addition of 3D ultrasound can enhance the detection of intraductal extension. Advances in knowledge: Choice of conservative breast surgery vs mastectomy is still a debate. We used an advanced, contrast-based, application of the mammogram: CESM and a non-invasive 3D breast ultrasound in the assessment of the local extension of the breast cancer regarding size, perifocal stromal infiltration and multiplicity to guide the selection of proper management in proved cases of breast cancer.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Imagenología Tridimensional , Mamografía/métodos , Ultrasonografía Mamaria/métodos , Adulto , Anciano , Medios de Contraste , Femenino , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Estudios Prospectivos , Carga TumoralRESUMEN
AIM: A confirmed wild-type RAS tumor status is commonly required for prescribing anti-EGFR treatment for metastatic colorectal cancer. This noninterventional, observational research project estimated RAS mutation prevalence from real-world sources. MATERIALS & METHODS: Aggregate RAS mutation data were collected from 12 sources in three regions. Each source was analyzed separately; pooled prevalence estimates were then derived from meta-analyses. RESULTS: The pooled RAS mutation prevalence from 4431 tumor samples tested for RAS mutation status was estimated to be 43.6% (95% CI: 38.8-48.5%); ranging from 33.7% (95% CI: 28.4-39.3%) to 54.1% (95% CI: 51.7-56.5%) between sources. CONCLUSION: The RAS mutation prevalence estimates varied among sources. The reasons for this are not clear and highlight the need for further research.
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Biomarcadores de Tumor/genética , Neoplasias Colorrectales/patología , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/mortalidad , Exones , Humanos , Mutación , Prevalencia , Proteínas Proto-Oncogénicas B-raf/genética , Tasa de SupervivenciaRESUMEN
BACKGROUND: The aim of this study was to determine and evaluate the association of different viral infections, with hepatitis B and C viruses, Epstein-Barr virus, cytomegalovirus and human herpes virus-8 (HBV, HCV, EBV, CMV, HHV-8) with the risk of lymphomas (Hodgkin and non-Hodgkin) among Egyptian patients, and correlate with the histopathological staging and typing as well as the prevalence of combined infections. MATERIALS AND METHODS: A total of 100 newly diagnosed lymphoma patients with 100 healthy age and sex matched normal controls were assayed for viral infection using enzyme linked immunosorbant assay (ELISA) followed by real time polymerase chain reaction (RT-PCR). RESULTS: Our results showed a high statistical significant difference between cases and controls as regards clinical and laboratory findings (<0.001 and=0.003). A high statistical difference was seen for the association of most viruses and lymphoma cases (<0.001) except for positive HBs Ag, positive CMV IgG and HHV-8 (p=0.37, 0.70 and 1.0 respectively). No statistical significant difference was found between Hodgkin (HL) and non-Hodgkin (NHL) as regards viral prevalence except HCV antigen, 57.1% for HL and 26.5% for NHL (p = 0.03). Only, HBV DNA showed a high significant value among infiltrated bone marrow cases (p=0.003) and finally, a high significant association of 2 combined viral infections with infiltrated bone marrow lymphoma cases (p=0.04). CONCLUSIONS: Our results showed that infection with HBV, HCV, CMV and EBV were associated with increased risk of lymphoma among the Egyptian population. Detection of new associations between infectious agents and risk of cancer development will facilitate progress in elaboration of prophylactic measures, early diagnostic methods and, hopefully, novel therapy of malignant tumours.
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Linfoma/etiología , Virosis/complicaciones , Virus/patogenicidad , Estudios de Casos y Controles , ADN Viral/genética , Egipto/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Linfoma/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prevalencia , Pronóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Riesgo , Virosis/virología , Virus/genéticaRESUMEN
BACKGROUND: The incidence of rectal cancer recurrence after surgery is 5-45%. Extended pelvic resection which entails En-bloc resection of the tumor and adjacent involved organs provides the only true possible curative option for patients with locally recurrent rectal cancer. AIM: To evaluate the surgical and oncological outcome of such treatment. PATIENTS AND METHODS: Between 2006 and 2012 a consecutive series of 40 patients with locally recurrent rectal cancer underwent abdominosacral resection (ASR) in 18 patients, total pelvic exenteration with sacral resection in 10 patients and extended pelvic exenteration in 12 patients. Patients with sacral resection were 28, with the level of sacral division at S2-3 interface in 10 patients, at S3-4 in 15 patients and S4-5 in 3 patients. RESULTS: Forty patients, male to female ratio 1.7:1, median age 45 years (range 25-65 years) underwent extended pelvic resection in the form of pelvic exenteration and abdominosacral resection. Morbidity, re-admission and mortality rates were 55%, 37.5%, and 5%, respectively. Mortality occurred in 2 patients due to perineal flap sepsis and massive myocardial infarction. A R0 and R1 sacral resection were achieved in 62.5% and 37.5%, respectively. The 5-year overall survival rate was 22.6% and the 4-year recurrence free survival was 31.8%. CONCLUSION: Extended pelvic resection as pelvic exenteration and sacral resection for locally recurrent rectal cancer are effective procedures with tolerable mortality rate and acceptable outcome. The associated morbidity remains high and deserves vigilant follow up.
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Exenteración Pélvica , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Región Sacrococcígea , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Exenteración Pélvica/métodos , Complicaciones Posoperatorias , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/mortalidad , Región Sacrococcígea/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Neuroendocrine tumors (NETs) arise in most organs of the body and share many common pathologic features. However, a variety of organ-specific systems have been developed for nomenclature, grading and staging of NETs, causing much confusion. In collaboration with WHO, the European Neuroendocrine Tumor Society (ENETS) recommended the use of either mitotic rate or Ki-67 labeling index (LI) for grading and classification. We aim to explore the profile of NETs in Egyptian patients and apply the ENETS system. MATERIALS AND METHODS: This retrospective study was carried out on all cases of NETs diagnosed at the Pathology Department, National Cancer Institute, Cairo University, during the period from January 2000 to December 2009. Data about age, sex, anatomic site of tumor, tumor size, tumor stage and presence of nodal metastasis were retrieved. Ki-67 immunostaining and grading according to ENETS were done. RESULTS: There was a trend toward increased mean age and tumor size and grade according to Ki-67, with significant statistical difference (p < 0.001 and 0.036, respectively). Estimation of mitotic count and Ki-67 LI was strongly associated with NET histopathologic types, but this association was stronger regarding Ki-67 LI than mitotic count (p = 0.002 and 0.035, respectively). On the other hand, there was discordance between grading according to mitotic count and grading according to Ki-67 LI in relation to NET histopathologic subtypes. Concordance between mitotic rate and Ki-67 LI was reported in 18.89% of cases, while discordance occurred in 81.11% of cases and was more prevalent in G3. CONCLUSION: Ki-67 is a reliable and reproducible marker for grading of NETs and more superior than mitotic rate.
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Biomarcadores de Tumor/metabolismo , Antígeno Ki-67/metabolismo , Tumores Neuroendocrinos/patología , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Índice Mitótico , Necrosis , Clasificación del Tumor , Estadificación de Neoplasias , Tumores Neuroendocrinos/metabolismo , Pronóstico , Estudios Retrospectivos , Factores de TiempoRESUMEN
The high incidence and mortality of lung carcinoma in Egypt necessitates studying the factors that may be implicated in non-small cell lung carcinoma (NSCLC) pathogenesis and could affect patient management. The aim was to study FHIT, epidermal growth factor receptor (EGFR), and MSH2 protein expression in Egyptian patients with NSCLC. Immunohistochemical staining for FHIT, EGFR, and MSH2 was performed on 64 specimens from NSCLC patients and correlated with prognostic parameters, response to therapy, and overall survival. FHIT loss was observed in 64% of NSCLC patients and was significantly associated with SCC (P=0.003) and poor tumor grade (P=0.043). EGFR overexpression was observed in 47% of NSCLC patients and was significantly associated with SCC (P=0.002). MSH2 was reduced in 23.4% of NSCLC patients and was significantly associated with adenocarcinoma (P=0.024). In a univariate analysis, a significant relationship was seen between the poor overall survival in NSCLC patients and high T-stage (P=0.029), presence of metastasis (P=0.014), advanced-stage grouping (P=0.004), and FHIT loss (P=0.033). Further, FHIT loss was significantly related to disease progression in patients treated with chemotherapy (P=0.038). We conclude that all 3 markers play a role in the development of NSCLC in Egyptian patients. We suggest that FHIT loss be used as a predictor for progression in chemotherapy-treated NSCLC patients.
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Ácido Anhídrido Hidrolasas/genética , Adenocarcinoma/diagnóstico , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Receptores ErbB/genética , Neoplasias Pulmonares/diagnóstico , Proteína 2 Homóloga a MutS/genética , Proteínas de Neoplasias/genética , Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Análisis de SupervivenciaRESUMEN
INTRODUCTION: Breast cancer (BC) is a major health problem in Egypt and worldwide. Its prognosis depends not only on tumor stage but also on tumor biology. AIM: To correlate the expression of Ki67 with the clinical outcomes of early hormone-receptor positive postmenopausal BC patients who are receiving tamoxifen. METHODS: This cohort study included 70 patients. They were followed up for a minimum of 2 years. Ki67 was assessed on paraffin-embedded blocks using immunohistochemistry methods. RESULTS: The median Ki67 value was 22.5% (IQR, 10%-50%). Ki67 was significantly higher in patients with HER2 positive tumors compared to HER2 negative tumors. After a median follow up period of 53 months, 22 patients (31%) developed disease recurrence either loco-regional or distant in 5.7% and 30%, respectively. Recurrent patients had significantly higher tumor stage, nodal stage and Ki67 values compared to non-recurrent cases. The 2-, 3- and 5-year overall survival (OS) and disease-free survival (DFS) rates were 100% & 91%, 98% & 84% and 77% & 59%, respectively. DFS was significantly worse with higher TNM stage, lower ER expression and higher Ki67 values. OS was significantly worse in patients with Ki67 values ≥ 30%. Ki67 ≥ 30% was an independent predictor of recurrence, poor DFS and OS. CONCLUSION: High Ki67 expression is predictive of poor prognosis and of resistance to adjuvant tamoxifen therapy in postmenopausal BC. We recommend considering Ki67 as one of the risk factors that guide adjuvant treatment decisions.
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Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Resistencia a Antineoplásicos , Antígeno Ki-67/metabolismo , Tamoxifeno/uso terapéutico , Anciano , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Resistencia a Antineoplásicos/genética , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Antígeno Ki-67/genética , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Posmenopausia , Estudios Prospectivos , RecurrenciaRESUMEN
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of NHL in Egypt. It represents about 49% of NHL presenting to the National Cancer Institute (NCI), Cairo University. CHOP regimen is the standard treatment used for NHL since the 1970s with only 30-40% overall survival. Recently, integration of Rituximab became a standard of care for patients with DLBCL. However, its widespread use in developing countries is still limited by the lack of financial coverage. Clinical prognostic factors, as well as the pathological markers, are mandatory to individualize treatment. AIM: The aim of the study was to evaluate the clinical risk stratification models including the age adjusted International prognostic index (aaIPI), patients profile and dose intensity (DI) of Cyclophosphamide and Doxorubicin as effective tools for predicting the outcome and prognosis of our DLBCL patients treated with first line CHOP regimen. PATIENTS AND METHODS: This retrospective study included 224 patients with diffuse large B cell lymphoma who were treated with 3-8 cycles of CHOP regimen at the Medical Oncology Department, NCI, Cairo University during the time period from 1999 to 2006. RESULTS: One hundred and seventy-eight patients (79.5%) achieved CR after the CHOP regimen with an observation period of 51 months. The median survival time was 12 months. The OS and DFS at 2 years were 82% and 68.8%, respectively. The univariate analysis of predictive factors for response to treatment showed that the CR rate was significantly affected by aa-IPI and its elements (performance status, stage & LDH), extranodal lesions and DI of Cyclophosphamide and Doxorubicin. The CR rate was 96.9%, 91.2%, 73.9% and 55.6% in cases with aa-IPI 0, 1, 2 and 3, respectively (p<0.001) and it was 82.4%, 81.9% versus 50% in cases with no extranodal site, one extranodal site and two extranodal sites, respectively (p=0.01). As regard DI of Cyclophosphamide, with DI below or equal to the median (249 mg/m(2)/week) the CR rate was 69%, while with DI above the median the CR rate was 87.7% (p=0.001). For Doxorubicin, the CR rate was 72.3% with DI below or equal to the median (16.5 mg/m(2)/week), however, it was 86.6% with DI above the median (p=0.008). The OS rate was significantly affected by aa-IPI as it was 89.8% in cases of aa-IPI 0+1 versus 75.8% in those of aa-IPI 2+3 (p=0.03). DI of Cyclophosphamide and Doxorubicin significantly influenced the OS. The OS rate was 74% with DI of Doxorubicin below or equal to the median versus 96% in cases with DI above the median (p=0.02). For Cyclophosphamide the OS rate was 72.7% with DI below or equal to the median versus 96.3% in cases with DI above the median (p=0.01). The tumor bulk (with a median tumor size of 5 cm) affected the OS, which was 91.23% versus 86.8% in the tumor bulk less than and more than or equal to the median, respectively (p=0.05). By multivariate analysis of predictive factors for response to treatment, the CR rate was significantly affected by the number of extranodal sites and the clinical staging of diffuse large B cell lymphoma. However, OS rate was strongly associated with the bulk of the tumor and the clinical staging of diffuse large B cell lymphoma. CONCLUSION: DI of Cyclophosphamide and Doxorubicin is important in the future treatment regimen plan for DLBCL especially in high risk cases. In addition to aa-IPI and its elements, extra nodal sites and bulk of the tumor proved to be significant predictors and prognostic factors for DLBCL treatment outcome.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/diagnóstico , Adolescente , Adulto , Ciclofosfamida/uso terapéutico , Supervivencia sin Enfermedad , Doxorrubicina/uso terapéutico , Femenino , Humanos , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prednisona/uso terapéutico , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Vincristina/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: Malignant pleural mesothelioma (MPM) is an asbestos related aggressive tumor. Asbestos causes genetic modifications and cell signaling events that favor resistance to chemotherapy. A variety of receptor tyrosine kinases have been identified to play a central role in various aspects of tumorigenesis. Epidermal growth factor receptor (EGFR) is overexpressed in a variety of epithelial malignancies including lung cancer in which EGFR aberrations not only predict response to EGFR tyrosine kinase inhibitors but also indicate tumor progression. However in MPM, the role of EGFR is less clear. This study was designed to identify serum and tissue EGFR levels in patients with MPM and to evaluate the relationship between serum and tissue EGFR levels and clinicao-pathological prognostic factors and survival. METHODS: We investigated 71 cases of MPM for EGFR expression in tissue. Serum EGFR was assessed in 40 out of those 71 cases and 20 healthy subjects as a control. Pre-treatment serum EGFR levels were measured using quantitative enzyme-linked immunosorbent assay. Tissue EGFR protein overexpression was assessed by immunohistochemistry and gene amplification was assessed by the chromogen in situ hybridization (CISH) technique. Results were correlated with the clinical-pathological factors of the patients and overall survival (OS). RESULTS: Out of the 71 patients included in the study, 19 had undergone extrapleural pneumonectomy. As for the rest of the patients, 46 received chemotherapy while 6 had only best supportive care. EGFR immuno-reactivity was detected in 74.6% of the cases, 37 (52.1%) cases were positive for EGFR gene amplification by CISH, 31 of them revealed moderate to high (++, +++) EGFR immuno-reactivity. Elevated serum EGFR >2.5 ng/ml (the median concentration of EGFR in MPM) was reported in 45% of the cases. The overall response rate (RR) for the 46 treated patients who received chemotherapy was 24.1%. After a median follow up of 29 months, the median overall survival (OS) was 10 months. Elevated serum and tissue EGFR is significantly associated with advanced disease stage. However neither EGFR overexpression in tissues nor high serum levels were associated with survival rates. CONCLUSIONS: EGFR expression is a common feature in MPM patients. High pre-treatment levels of serum EGFR are associated with advanced stage but not with reduced OS. Detailed mutational analysis of EGFR on a larger number of patients is still needed to clarify the exact role of EGFR in MPM patients.
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Biomarcadores de Tumor/biosíntesis , Receptores ErbB/biosíntesis , Mesotelioma/enzimología , Neoplasias Pleurales/enzimología , Adulto , Anciano , Biomarcadores de Tumor/sangre , Estudios de Casos y Controles , Receptores ErbB/sangre , Receptores ErbB/genética , Femenino , Amplificación de Genes , Humanos , Masculino , Mesotelioma/genética , Mesotelioma/patología , Persona de Mediana Edad , Neoplasias Pleurales/genética , Neoplasias Pleurales/patología , Pronóstico , Estudios Prospectivos , Análisis de Supervivencia , Adulto JovenRESUMEN
PURPOSE: The aim of this work is to determine the possible relationship between the different profiles of molecular expression of hormone receptors and Her-2÷neu receptors to clinical and histopathological known prognostic variables for breast cancer. MATERIALS AND METHODS: A total of 110 breast carcinoma tumor samples were included. In this study 4 groups or immunohistochemical profiles were defined, based on expression of hormone receptors (estrogen and÷or progesterone) and÷or Her2÷neu (Luminal A, Luminal B, HER2 overexpressing profile, and triple-negative profile). We studied whether there were differences between them regarding clinical and histopathological variables with a known prognostic significance in addition to Nottingham Prognosis Index (NPI). RESULTS: In this series, 65 cases corresponded to Luminal A (59.1%), 18 cases (16.4%) were Luminal B, in 14 cases (12.7%) HER2 was over-expressed, while 13 cases (11.8%) were of the triple negative subtype. It is worth noting the relationship between the triple negative and HER2 over-expressing immunophenotypes and the high NPI (>3.4) in comparison with the Luminal A and Luminal B immunophenotypes (p=.029). The association of the former two types with higher tumor grade was also observed, but such association did not reach statistical significance. CONCLUSION: The subgroups without hormone receptor expression, with Her2÷neu overexpression or without (triple-negative group), have characteristics associated with variables of a poorer prognosis. KEY WORDS: Breast cancer- Hormone receptors- Her2neu- Classification- Nottingham prognosis index.
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OBJECTIVE: Non-Hodgkin's lymphomas (NHL) are etiologically heterogeneous malignancies. In Egypt, we previously reported an association of increased NHL risk with chronic hepatitis C virus (HCV) infection. Our present aim is to assess the association between HCV infection and histological subtypes of NHL. METHODS: We conducted a case-control study at the National Cancer Institute of Cairo University. Cases with NHL (n = 486) were matched to controls (n = 786) who were orthopedic patients from the same referral regions. Participants provided a blood sample for HCV markers (anti-HCV, HCV RNA) and answered a questionnaire on possible risk factors. Case-control differences were assessed by odds ratios and 95% confidence intervals from logistic regression analysis. RESULTS: Cases with diffuse large B cell lymphoma (n = 146), chronic lymphocytic leukemia (n = 58), marginal zone lymphoma (n = 24), follicular lymphoma (n = 23), and mantle cell lymphoma (n = 16) were recruited. HCV RNA prevalence was 27% in controls and 26%-48% in the NHL subgroups: it was associated (p < 0.001) with diffuse large B cell, marginal zone, and follicular lymphomas with odds ratios of 3.2, 4.4, and 3.3, respectively. CONCLUSION: HCV is a risk factor for diffuse large B cell, marginal zone, and follicular lymphomas in Egypt.
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Hepatitis C Crónica/complicaciones , Linfoma de Células B de la Zona Marginal/virología , Linfoma Folicular/virología , Linfoma de Células B Grandes Difuso/virología , ARN Viral/sangre , Estudios de Casos y Controles , Intervalos de Confianza , Egipto/epidemiología , Humanos , Inmunohistoquímica , Inmunofenotipificación , Entrevistas como Asunto , Modelos Logísticos , Linfoma de Células B de la Zona Marginal/epidemiología , Linfoma Folicular/epidemiología , Linfoma de Células B Grandes Difuso/epidemiología , Oportunidad Relativa , Prevalencia , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
BACKGROUND: Clinical characterization of bladder carcinomas is still inadequate using the standard clinico-pathological prognostic markers. We assessed the correlation between nm23-H1, Rb, EGFR and p53 in relation to the clinical outcome of patients with muscle invasive bilharzial bladder cancer (MI-BBC). METHODS: nm23-H1, Rb, EGFR and p53 expression was assessed in 59 MI-BBC patients using immunohistochemistry and reverse transcription (RT-PCR) and was correlated to the standard clinico-pathological prognostic factors, patient's outcome and the overall survival (OS) rate. RESULTS: Overexpression of EGFR and p53 proteins was detected in 66.1% and 35.6%; respectively. Loss of nm23-H1and Rb proteins was detected in 42.4% and 57.6%; respectively. Increased EGFR and loss of nm23-H1 RNA were detected in 61.5% and 36.5%; respectively. There was a statistically significant correlation between p53 and EGFR overexpression (p < 0.0001), nm23 loss (protein and RNA), lymph node status (p < 0.0001); between the incidence of local recurrence and EGFR RNA overexpression (p= 0.003) as well as between the incidence of metastasis and altered Rb expression (p = 0.026), p53 overexpression (p < 0.0001) and mutation (p = 0.04). Advanced disease stage correlated significantly with increased EGFR (protein and RNA) (p = 0.003 & 0.01), reduced nm23-H1 RNA (p = 0.02), altered Rb (p = 0.023), and p53 overexpression (p = 0.004). OS rates correlated significantly, in univariate analysis, with p53 overexpression (p = 0.011), increased EGFR (protein and RNA, p = 0.034&0.031), nm23-H1 RNA loss (p = 0.021) and aberrations of > or = 2 genes. However, multivariate analysis showed that only high EGFR overexpression, metastatic recurrence, high tumor grade and the combination of > or = 2 affected markers were independent prognostic factors. CONCLUSION: nm23-H1, EGFR and p53 could be used as prognostic biomarkers in MI-BBC patients. In addition to the standard pathological prognostic factors, a combination of these markers (> or = 2) has synergistic effects in stratifying patients into variable risk groups. The higher is the number of altered biomarkers, the higher will be the risk of disease progression and death.
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Biomarcadores de Tumor/biosíntesis , Receptores ErbB/biosíntesis , Nucleósido Difosfato Quinasas NM23/biosíntesis , Proteína de Retinoblastoma/biosíntesis , Proteína p53 Supresora de Tumor/biosíntesis , Neoplasias de la Vejiga Urinaria/metabolismo , Adulto , Anciano , Biomarcadores de Tumor/genética , Receptores ErbB/genética , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Nucleósido Difosfato Quinasas NM23/genética , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Esquistosomiasis/genética , Esquistosomiasis/metabolismo , Esquistosomiasis/patología , Tasa de Supervivencia , Proteína p53 Supresora de Tumor/genética , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/parasitología , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
UNLABELLED: The aim of the present study is to assess the frequency of bone marrow (BM) involvement by both bone marrow aspirate and biopsy (BMA and BMB, respectively) procedures in established cases of lymphomas at initial presentation, and to study the relative frequency of marrow disease in relation to lymphoma types, patterns of infiltration and the 2ry associated changes, as well as the diagnostic challenges. Moreover, the diagnostic validity of BMA is tested taking the results of the BMB as the true test results, in order to determine the role of each procedure in the diagnostic approach of marrow infiltration. PATIENTS AND METHOD: This is a retrospective study carried out on 143 nonconsecutive Egyptian patients with lymphomas obtained from a private series during the years 2005 to 2008. Criteria of inclusion included the availability of full medical records and material (medical and pathological), patient consent, nodal disease with no therapy prior to BM sampling, except in 7 patients who had another 2nd BMB following therapy. BMA and BMB were performed as part of the routine workup for diagnosis and staging of lymphoma. The patients had a male to female sex ratio of 2.6:1 and a wide age range from 4 to 74 years. RESULTS: In the present series, 64 cases out of the 143 lymphoma patients studied (44.8%) had a BM disease. Involvement was mostly bilateral (80%). Patients older than 40 years showed higher incidence of bone marrow involvement. There was complete concordance (100%) between both diagnostic procedures in the detection of 76 marrow disease-free lymphoma patients. BMA showed no false positive results and a low rate of deference that makes of it an ideal screening test. Three deferred smears of CLL for BMB diagnosis were all positive for involvement. However, in a total number of 64 BMB positive patients, aspirates could only identify lymphoma involvement in 42 lymphoma patients and missed 22 patients with a BM disease, with an overall sensitivity rate of 65.6%. BMB had a high diagnostic viability and is an easily applied reproducible procedure for diagnosis of BM involvement based on a more detailed informative analysis of both architectural and individual cytomorphologic changes. CONCLUSION: The relatively high level of BM involvement in Egyptian lymphoma patients was directly proportional to high-risk factors. The diagnostic validity of BMB is higher than that of BMA. However, BMA serves as a good positive test in screening lymphomas for marrow disease. A negative BMA does not exclude involvement. Thus, smears should be taken as a complimentary procedure.
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Enfermedades de la Médula Ósea/patología , Médula Ósea/patología , Linfoma/patología , Adolescente , Adulto , Anciano , Biopsia , Enfermedades de la Médula Ósea/diagnóstico , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Background : Composite lymphoma (CL) is a rare disease that has been identified in recent literature. The term composite lymphoma was first proposed to denote the occurrence of more than one lymphoma in a single patient; however, the present accepted definition is the occurrence of 2 or more distinct lymphoma types in a single anatomic site. The condition could be concurrent or sequential. Unlike disease progression or transformation in lymphoma, CL should include two distinct clones proven by morphological and laboratory tests. Pathogenesis : No single definite mechanism has been suggested to explain the pathogenesis of the different types of CL. The etiology is variable, complex and differs according to the types of lymphomas involved. Several theories were proposed including clonal selection with additional mutational accumulation, genomic instability with genetic predisposition, common precursor cell and the aid of a viral factor, mostly EBV. Diagnosis : The morphologic criteria must be confirmed by one or more tests including immunohistochemistry, flow cytometry, gene rearrangement by PCR, cytogenetics, FISH, in-situ hybridization, DNA sequencing and cDNA microarray . Results are more accurate using the laser capture microdissection method. Many combinations of CL are reported, including : Multiple B-cell lymphomas; B-cell and T-cell lymphomas; NHL and HL; or complex B-cell, T-cell and HL cases. Conclusion : Due to the great advancement in molecular characterization of lymphoma, CL is being increasingly identified. It must be carefully diagnosed, because the multiple disease entities may have entirely different natural histories, prognosis and treatment modalities. Also, careful study of such cases may clarify the possible pathogenic mechanisms of the interrelationship of clonal evolution in lymphoma. Key Words : Composite lymphoma -EBV.
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BACKGROUND: Improvement of current results of therapy for large cell non-Hodgkin lymphoma patients can be achieved by optimization of initial treatment or application of risk-adapted therapy. The international prognostic index ( IPI), introduced to identify high-risk patients, was recently criticized because it was based on clinical risk factors only, ignoring important tumor molecular risk factors and it fails to identify a sector of high-risk patients, who ultimately relapse. OBJECTIVE: The aim of this study is to evaluate the value of two tumor biomarkers:MIB-1 and p53 as potential risk factors in diffuse large cell lymphoma. MIB-1 measures tumor cell proliferation, whereas p53 is related to tumor progression and response to chemotherapy. PATIENTS AND METHODS: The study was done on 69 adult patients with diffuse large cell NHL ( 58 B-phenotype and 11 T-phenotype). Clinical risk assessment was determined by the IPI and patients with a score of 3 or more were considered high-risk. Expression of MIB-1 and p53 was determined by immunohistochemistry and nuclear staining was quantitated by image analysis. Immunoexpression was considered high for MIB-1 nuclear count 50% and p53 counts 20%. Evaluation included both response to chemotherapy ( mostly CHOP), as well as 2- year overall survival analysis. RESULTS: The IPI was the only clinical variable which had a significant impact on survival. Overexpression of both MIB-1 and p53 was associated with poor response to treatment, as well as unfavorable survival. Combined risk factor analysis revealed that only MIB-1 was an independent variable. MIB-1 could also identify some high-risk patients previously categorized in the IPI lowrisk group. CONCLUSIONS: MIB-1 is an independent biologic risk factor for large cell NHL. In order to optimize risk assessment of these patients, it is recommended to construct a new prognostic index by adding MIB-1 overexpression to the other clinical factors of standard IPI. This may allow better identification of high-risk patients and help to guide planning of effective initial treatment. Key Words:NHL - MIB-1 - p53 - CHOP - Risk factors.
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Antígeno Ki-67/metabolismo , Linfoma de Células B Grandes Difuso/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Adulto , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Inmunohistoquímica , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Pronóstico , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To explore any changes in bladder carcinoma during 37 years period, in regard to: its frequency, bilharzia association, histological profile and demographic data. PATIENTS AND METHODS: This is a retrospective study on 9843 patients treated at the National Cancer Institute (NCI), Cairo University, during the years 1970-2007. Three groups were selected: series (A) included 3212 patients during 1970-1974, series (B) 3988 patients during 1985-1989 and series (C) 2643 patients during 2003-2007. For statistical analysis, data of series (A), (B) and (C) were compared to determine the significance of difference (p value 0.005). RESULTS: A significant decline of the relative frequency of bladder cancer was observed from 27.63% in the old series to 11.7% in the recent series. Bilharzia association dropped from 82.4% to 55.3%. There was a significant rise of transitional cell carcinomas from 16.0% to 65.8%, becoming at present the most common tumor type, with a significant decrease in squamous cell carcinomas from 75.9% to 28.4%. There was an increase in the median age of patients from 47.4 years to 60.5 years and a decrease of male: female (M/F) ratio from 5.4 to 3.3. CONCLUSIONS: The decline in the relative frequency of bladder cancer is associated with a decline in bilharzia egg positivity in the specimen and is probably related to better control of bilharziasis in the rural population in Egypt. This was accompanied by a change in the histological profile of tumors, with significant predominance of transitional cell carcinoma and an increase in the age of patients, a pattern rather similar to that in western reports.
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Carcinoma de Células Escamosas/epidemiología , Schistosoma/patogenicidad , Esquistosomiasis/epidemiología , Neoplasias de la Vejiga Urinaria/epidemiología , Animales , Carcinoma de Células Escamosas/patología , Carcinoma de Células Transicionales/epidemiología , Carcinoma de Células Transicionales/patología , Egipto/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Esquistosomiasis/patología , Factores de Tiempo , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: Human papillomavirus (HPV) types 16 and 18 are associated with cervical carcinogenesis. This is possibly achieved through an interaction between HPV oncogenic proteins and some cell cycle regulatory genes. However, the exact pathogenetic mechanisms are not well defined yet. METHODS: We investigated 110 subjects (43 invasive squamous cell carcinoma (ISCC), 38 CIN III, 11 CIN II, 18 CIN I) confirmed to be positive for HPV16 and/or 18 as well as 20 normal cervical tissue (NCT) samples for abnormal expression of cyclin D1, cyclin E, CDK4, cyclin inhibitors (p21 (waf), p27, p16 (INK4A)) and Ki-67 using immunohistochemistry and differential PCR techniques. RESULTS: There was a significant increase in the expression of Ki-67, cyclin E, CDK4, p16 (INK4A) (p=0.003, 0.001, 0.001) and a significant decrease in p27 (Kip1) from NCT to ISCC (p=0.003). There was a significant correlation between altered expression of p27 (KIP1) and p16(INK4A) (p<0.001), cyclin D1 and CDK4 (p=0.001), cyclin E and p27 (Kip1) (p=0.011) in all studied groups. In ISCC, there was significant relationship between standard clinicopathological prognostic factors and high Ki-67 index , increased cyclin D1 and cyclin E, reduced p27 (Kip1) and p21 (waf). CONCLUSION: 1) Aberrations involving p27 (KIP1), cyclin E, CDK4 and p16 (INK4A) are considered early events in HPV 16 and 18-associated cervical carcinogenesis (CINI & II), whereas cyclin D1 aberrations are late events (CINIII & ISCC) 2) Immunohistochemical tests for p16 (INK4A) and cyclin E could help in early diagnosis of cervical carcinoma 3) Only FIGO stage, cyclin D1, p27 (Kip1) and Ki-67 are independent prognostic factors that might help in predicting outcome of cervical cancer patients.
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Carcinoma de Células Escamosas/patología , Proteínas Inhibidoras de las Quinasas Dependientes de la Ciclina/fisiología , Quinasas Ciclina-Dependientes/fisiología , Ciclinas/fisiología , Infecciones por Papillomavirus/complicaciones , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Proteína Quinasa CDC2/genética , Proteína Quinasa CDC2/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/enzimología , Carcinoma de Células Escamosas/genética , Ciclina E/genética , Ciclina E/metabolismo , Quinasa 4 Dependiente de la Ciclina/genética , Quinasa 4 Dependiente de la Ciclina/metabolismo , Proteínas Inhibidoras de las Quinasas Dependientes de la Ciclina/genética , Proteínas Inhibidoras de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Quinasas Ciclina-Dependientes/genética , Quinasas Ciclina-Dependientes/metabolismo , Ciclinas/genética , Ciclinas/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Genes bcl-1 , Genes p16 , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Infecciones por Papillomavirus/enzimología , Infecciones por Papillomavirus/genética , Células Tumorales Cultivadas , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/enzimología , Neoplasias del Cuello Uterino/genética , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/enzimología , Displasia del Cuello del Útero/genéticaRESUMEN
PURPOSE: A prospective study was designed to randomize locally advanced rectal carcinoma patients between either preoperative radiotherapy (+/- postoperative chemotherapy) or postoperative adjuvant chemoradiation. Two end points were evaluated, local recurrence and survival, aiming at defining prognostic parameters that can help in the choice of the optimum treatment modality. PATIENTS AND METHODS: This is a prospective randomized clinical study including patients with locally advanced low rectal cancer treated at the National Cancer Institute (NCI), Cairo University, during the period from December 1994 to January 1999. Fifty patients with previously untreated rectal cancer were randomized into two groups, Group I: Subjected to surgery followed by radiation therapy (50Gy/5 weeks, 2Gy/fraction, 5 days/week) plus chemotherapy and Group II, subjected to preoperative radiotherapy (46Gy/4.5 weeks, 2Gy/ fraction, 5 days/week) followed by surgery +/- postoperative chemotherapy. Chemotherapy in the concomitant setting was given in the form of Leucovorin in a dose of 300mg/m2 as a short i.v. infusion followed by 5-FU in a dose of 350mg/m2 as a 6 hour i.v. infusion, whereas adjuvant chemotherapy consisted of 5- FU as 600mg/m2 short i.v. infusion weekly for 48 weeks, in addition to levamisole tablets. RESULTS: The long-term treatment end results obtained showed that group I patients had a slightly higher 10-year overall survival (OS) rate when compared to group II patients (63% versus 60%, p=0.698). The corresponding figures for the 10-year disease-free survival (DFS) were 65% and 66%, respectively, p=0.816. Although the 10- year local failure rate (persistent/relapsed disease) was higher for the preoperative group, it was not of statistical significance, (30% Vs. 8%, p=0.057). On the other hand, the 10-year distant metastasis free survival was higher in the preoperative group (88% Vs. 72%), yet this difference did not reach statistical significance (p=0.16). The rate of acute radiation reactions was higher in the postoperative group, with no increase in the operative complications in the preoperative group. Moreover, none of the 50 patients had grade 3 or more late radiation/surgical squealae. There were no grade 3 or 4 chemotherapy related toxicities. CONCLUSIONS: This work showed equal results for DFS and OS rates between preoperative and postoperative radiation therapy with the same acceptable acute and late radiation toxicity. High dose preoperative irradiation did not cause any significant increase in acute or late radiation induced reactions, delay in wound healing or increased postoperative morbidity when compared to postoperative adjuvant radiochemotherapy. Duke' s stage and response to preoperative irradiation proved to be of significance regarding DFS, while compliance to systemic therapy was of significance regarding both OS and DFS.
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Carcinoma/mortalidad , Carcinoma/radioterapia , Cuidados Posoperatorios , Cuidados Preoperatorios , Neoplasias del Recto/mortalidad , Neoplasias del Recto/radioterapia , Adulto , Carcinoma/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioterapia Adyuvante , Neoplasias del Recto/cirugía , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: The particular goal of this work is to study some cell cycle regulatory proteins and their potential impact on prognosis of breast cancer; p53, cyclin D1 and p27 are potential effectors being the major contributors to the control of the restriction (R) check point of the cell cycle. We also aimed to evaluate different techniques used to detect these cell cycle proteins. MATERIAL AND METHODS: Forty five breast cancer patients as well as 10 controls with non malignant pathology were assessed for cell cycle regulators each by 2 different techniques; p53 was assessed by enzyme immunoassay (EIA) and immunohistochemistry (IHC), cyclin D1 by Western Blotting (WB) and IHC and p27 by WB and IHC. The cut-off was calculated as the mean of the normal controls +2 SD. Patients were followed up for 4 years and their laboratory data were correlated with different clinical parameters and with other studied regulators. RESULTS: Eighty seven percent of cases (39/45) were positive for p53 by EIA with a range from 20 to 4300, and a mean of 464 +/- 971 pg/mg protein. By IHC, 80% (24/30) of the cases showed varying degrees of positivity. Using WB, cyclin D1 showed high expression levels above cut off values in 69% of patients (31/45) and in 67% (20/30) by IHC. The corresponding positive figures for p27 were 82% (37/45) and 73% (22/30) using the two techniques, respectively. No significant association was found between p53, cyclin D1 and p27 on one side and different clinical parameters as lymph node status, tumor size or presence of distant metastases on the other side. Survival was poor in patients with high p53 expression. Cyclin D1 positive cases showed comparable survival with negative cases, whereas high p27 levels favored a longer disease free survival. CONCLUSIONS: Techniques more suitable for assessment of each of these markers in our consideration were EIA for p53, WB for cyclin D1 and IHC for p27. Moreover, this study demonstrated that these markers were relevant to the biological behavior of the tumor cell per se with a possible impact on prognosis and survival, independent of other clinical prognostic factors.
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Biomarcadores de Tumor/análisis , Neoplasias de la Mama/diagnóstico , Carcinoma/diagnóstico , Proteínas de Ciclo Celular/análisis , Western Blotting , Neoplasias de la Mama/patología , Carcinoma/patología , Egipto , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunohistoquímica , Estadificación de Neoplasias , PronósticoRESUMEN
OBJECTIVE: The aim of this study was to compare the standard prognostic factors of Hodgkin's lymphoma (HL) in relation to response to first line chemotherapy, disease free survival (DFS) and overall survival (OS). PATIENTS AND METHODS: The study was performed on a group of 100 adult patients diagnosed as HL and who were treated and followed-up in the years 1999 to 2001, in the Medical Oncology Department at National Cancer Institute (NCI), Cairo. The first line chemotherapy was COPP in 40%, ABVD in 35% and COPP/ABV hybrid in 25%. Patients were classified into early stage disease: Stages I, IIA and IIB without poor risk factors, n=43 and advanced stage disease: Stages III, IV and IIB with poor risk factors, n=57 analysis of the prognostic factors for early versus advanced-stage disease was done by univariate and multivariate regression analysis. RESULTS: Complete remission (CR) was attained in 69% of the patients after first line chemotherapy; being 87.8 % and 54.7% for early and advanced disease, respectively, (p=0.0001). The CR rates after different chemotherapy regimens were 81.8%, 90% and 90% for the ABVD, COPP and COPP/ABV hybrid regimens in the early-disease group; respectively; in contrast to the corresponding figures of 54.5%, 50% and 61.5% in the advanced- stage group. The DFS at 4 years, was 94 %, 55% and 54.5% for the patients treated with ABVD, COPP and COPP/ABV hybrid, respectively (p=0.2). The DFS and OS in this series of patients were 61.3% and 53.7%, being 69.8% and 70.7% for the early and 45.1% and 38.9% for the advanced-disease, respectively The OS of the whole group was significantly related to age (p=0.04), sex (p=0.005), early versus advanced disease (p=0.0001) and B symptoms (p=0.0006). CONCLUSIONS: The adequate response and DFS of the early compared to the advanced-stage disease supported the evolving role of risk adapted chemotherapy for HL. The prognostic factors proved to be of significant impact in our series. The results of this study pointed to the need for an improved treatment strategy in this potentially curable disease,especially for the advanced disease.