RESUMEN
BACKGROUND: Numerous novel genes have been identified in urothelial bladder cancer (UBC); genes including ninjurin, synuclein and neuropilin seem to be associated with invasive tumours and aggressive behaviour. AIMS: To define the protein expression of these biomarkers and to reveal their prognostic value in a large series of superficial (pTa) and minimally invasive (pT1) cases of UBC with a long and adequate follow-up. METHODS: Tissue microarray was done on 183 paraffin-embedded tumour tissues (pTa 81, pT1 102). Statistical analysis was performed to define the association between each of these biomarkers, clinical data and tumour outcomes. RESULTS: There was a statistically significant association between synuclein expression and tumour stage (p = 0.029). Ninjurin expression was significantly associated with tumour progression in univariate analysis. Tumour grade seemed to have an independent value in predicting tumour recurrence and progression. CONCLUSION: Tumours with strong synuclein expressions are more likely to be more advanced tumours (pT1). Tumours expressing ninjurin tend to progress slower than those with no ninjurin expressions. Synuclein and neuropilin failed to show any value in predicting tumour behaviour.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Moléculas de Adhesión Celular Neuronal/metabolismo , Citoplasma/metabolismo , Progresión de la Enfermedad , Métodos Epidemiológicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Proteínas de Neoplasias/metabolismo , Estadificación de Neoplasias , Factores de Crecimiento Nervioso/metabolismo , Pronóstico , Sinucleínas/metabolismo , Análisis de Matrices Tisulares/métodos , Neoplasias de la Vejiga Urinaria/patologíaAsunto(s)
Hibridación Genómica Comparativa , Neoplasias Primarias Múltiples/patología , Neoplasias Ováricas/patología , Neoplasias Uterinas/patología , Anciano , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Metástasis de la Neoplasia/diagnóstico , Metástasis de la Neoplasia/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias Ováricas/diagnóstico , Neoplasias Uterinas/diagnósticoRESUMEN
AIMS: To compare the sensitivity and specificity of the recently commercially available FLI-1 monoclonal (FLI-1m) antibody with the currently used antibodies [CD99 and FLI-1 polyclonal (FLI-1p)] in the diagnosis of Ewing's sarcoma/primitive neuroectodermal tumour (EWS/PNET) and to determine the diagnostic value of the EWSR1 (22q12) dual-colour, break-apart rearrangement probe fluorescence in situ hybridization (FISH) technique. MATERIALS AND METHODS: Forty-three cases of well-documented EWS/PNET and 15 non-EWS/PNET cases were retrieved from the archival files. Immunohistochemistry (IHC) for FLI-1p, FLI-1m and FISH analysis was performed. RESULTS: The most sensitive and specific test panel for the diagnosis of EWS/PNET is the combination of CD99 and FLI-1p. FISH had a very high specificity (100%) but only a moderate sensitivity (50%). CONCLUSION: The combination of CD99 and FLI-1p is the method of choice for the diagnosis of EWS/PNET. EWRS1 (22q12) dual-colour, break-apart rearrangement probe FISH should be used as a confirmatory test in addition to CD99 and FLI1-p due to its high specificity.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Antígenos CD/inmunología , Neoplasias Óseas/diagnóstico , Moléculas de Adhesión Celular/inmunología , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/inmunología , Tumores Neuroectodérmicos Primitivos/diagnóstico , Receptores Citoplasmáticos y Nucleares/genética , Receptores Citoplasmáticos y Nucleares/inmunología , Sarcoma de Ewing/diagnóstico , Antígeno 12E7 , Actinas , Algoritmos , Anticuerpos Antineoplásicos/inmunología , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Neoplasias Óseas/genética , Neoplasias Óseas/inmunología , Aberraciones Cromosómicas , Femenino , Humanos , Hibridación Fluorescente in Situ/métodos , Masculino , Proteínas de Neoplasias/inmunología , Tumores Neuroectodérmicos Primitivos/genética , Tumores Neuroectodérmicos Primitivos/inmunología , Valor Predictivo de las Pruebas , Curva ROC , Sarcoma de Ewing/genética , Sarcoma de Ewing/inmunología , TransactivadoresRESUMEN
AIMS: The study was designed to evaluate Raf1, Aurora-A/STK15 and E-cadherin (E-CD) protein expression and their prognostic value in patients with pTa/pT1 tumours. MATERIALS AND METHODS: A tissue microarray of 105 pTa, and 141 pT1 tumours was constructed and sections were immunostained with these three antibodies. RESULTS: There were significant associations between Raf1 overexpression and tumour grade (p = 0.03), between Aurora-A overexpression/alterations of E-CD and tumour grade and stage (p < 0.001 and p < 0.001). In multiple Cox regression analysis, moderate/strong expression of E-CD seemed to be an independent factor in predicting slower tumour progression (p = 0.003) and Aurora-A overexpression (p = 0.022) displays an independent value in predicting tumour recurrences. CONCLUSION: Evaluation of E-CD and Aurora-A expressions in tissue of patients with pTa/pT1 UC have been proven to be useful in predicting tumours behavior and Raf1 protein expression seemed to have no potential use in this regard.
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Biomarcadores de Tumor/biosíntesis , Cadherinas/biosíntesis , Carcinoma/metabolismo , Proteínas Serina-Treonina Quinasas/biosíntesis , Proteínas Proto-Oncogénicas c-raf/biosíntesis , Neoplasias de la Vejiga Urinaria/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Aurora Quinasa A , Aurora Quinasas , Carcinoma/patología , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , Estudios Retrospectivos , Análisis de Matrices Tisulares , Neoplasias de la Vejiga Urinaria/patología , Urotelio/patologíaRESUMEN
AIMS: This study is designed to evaluate the expression and prognostic value of FGFR3 protein expression in patients with pTa/pT1 tumours and to determine the significance of the combinations of FGFR3 and p53 protein expressions in bladder pathogenesis. MATERIALS AND METHODS: A tissue microarray (TMA) of 107 pTa, and 147 pT1 tumours was constructed. The TMA sections were immunostained with FGFR3 and p53 monoclonal antibodies. RESULTS: There were significant associations between loss of FGFR3 and tumour stage (p<0.001) and grade (p<0.001) and between p53 overexpression and tumour stage and grade (p<0.001 and p<0.001, respectively). There was no association between FGFR3 and p53 proteins (p=0.107). In addition, tumours with FGFR3+/p53- phenotype have slower recurrence rate than other (FGFR3+/p53+, FGFR3-/p53- and FGFR3-/p53+). CONCLUSION: 1-FGFR3 expression is significantly associated with two important prognostic factors; stage and grade. 2-FGFR3 protein expression is not an independent predictive factor for pTa/pT1 tumour recurrence and progression. 3-Tumours with FGFR3+/p53- phenotype seem to have a distinctive pathway in bladder tumorigenesis.
Asunto(s)
Carcinoma de Células Transicionales/química , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/análisis , Proteína p53 Supresora de Tumor/análisis , Neoplasias de la Vejiga Urinaria/química , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Anticuerpos Monoclonales , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/terapia , Quimioterapia Adyuvante , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/química , Estadificación de Neoplasias , Fenotipo , Pronóstico , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/inmunología , Estudios Retrospectivos , Proteína p53 Supresora de Tumor/inmunología , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/terapia , Procedimientos Quirúrgicos UrológicosRESUMEN
AIMS: To determine the frequency of point mutation in c-kit in CD117+ small cell lung cancer (SCLC). A significant proportion of SCLCs have been documented to be CD117+, thereby signifying they express the c-kit gene product. This finding suggests this tumour may be a potential target for tyrosine kinase inhibitor (TKI) agents directed at c-kit. A point mutation in exon 17 of the c-kit gene, however, can abrogate the binding of TKIs. This being the case, immunohistochemistry is necessary to identify potential candidates for treatment with TKIs, but DNA sequence analysis may need to be performed to determine if these tumours will respond. METHODS AND RESULTS: Tumour cells of 23 cases of SCLC showing immunoreactivity for CD117 were laser capture microdissected from archived formalin-fixed paraffin-embedded tissue and the DNA isolated. PCR on exon 17 of the c-kit gene was performed and the amplified product sequenced. No point mutations were detected. CONCLUSIONS: The absence of mutations in exon 17 of CD117+ SCLC suggests this tumour may respond to therapy with TKI.
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Carcinoma de Células Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogénicas c-kit/genética , Carcinoma de Células Pequeñas/genética , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/genética , Mutación Puntual , Reacción en Cadena de la Polimerasa , Proteínas Proto-Oncogénicas c-kit/metabolismo , Estudios RetrospectivosRESUMEN
BACKGROUND: The peripheral benzodiazepine receptor (PBR) is an 18-kDa protein receptor mainly found on the outer mitochondrial membrane of cells. The PBR plays a role in several cellular functions including haem synthesis, steroidogenesis, DNA synthesis, cell growth and differentiation, and apoptosis. PBR expression in normal skin correlates with proliferating, secretory and differentiated cellular structures. Increased or aberrant expression of PBR has been associated with aggressive behaviour in several tumour types including ovarian, colon and breast adenocarcinomas and glioblastoma. OBJECTIVES: To determine whether changes in normal PBR distribution would be useful as markers for skin cancers or possible target sites for therapies such as photodynamic therapy (PDT), we used immunohistochemistry to evaluate PBR expression and distribution in normal and photodamaged skin (actinic keratoses), skin cancers (in situ and invasive squamous cell carcinomas and superficial, nodular, morphoeiform and mixed pattern basal cell carcinomas) and several benign epithelial proliferations. METHODS: A rabbit polyclonal antibody to a synthetic peptide fragment of the PBR was developed and characterized by enzyme-linked immunosorbent assay and Western blot analysis. The antibody was used to stain formalin-fixed and paraffin-embedded tissue samples (n = 157) by a routine avidin-biotin immunohistochemical technique. Sections were evaluated for antibody localization, distribution (0-4+) and reaction intensity (negative to strong). RESULTS: Normal skin stained with a strong homogeneous positive reaction (3-4+) in the spinous and granular layers (with a gradient corresponding to increasing differentiation), the pilosebaceous units, eccrine gland ducts, endothelial cells and pilar muscle. In cutaneous neoplasms and other skin diseases, a heterogeneous pattern (0-4+) of PBR expression at lower intensity was seen depending on tumour type and degree of differentiation. PBR expression was greatest in well-differentiated tumours, synonymous with the PBR expression gradient seen in normal skin; and least in poorly differentiated and infiltrative tumour types. CONCLUSIONS: The haem biosynthetic pathway has been harnessed for PDT of skin carcinomas by application of exogenous aminolaevulinic acid to generate the endogenous photosensitizer protoporphyrin IX (PpIX). Owing to the role of PBR as a transporter of haem precursors in haem synthesis, PBR density and distribution in skin cancers could be a predictor of the capacity for PpIX production and subsequent response to PDT in skin cancers.
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Biomarcadores de Tumor/metabolismo , Receptores de GABA-A/metabolismo , Neoplasias Cutáneas/metabolismo , Piel/metabolismo , Western Blotting/métodos , Carcinoma Basocelular/metabolismo , Carcinoma de Células Escamosas/metabolismo , Humanos , Queratosis/metabolismo , Proteínas de Neoplasias/metabolismo , Fotoquimioterapia , Trastornos por Fotosensibilidad/metabolismo , Lesiones Precancerosas/metabolismo , Pronóstico , Enfermedades de la Piel/metabolismoRESUMEN
BACKGROUND: Surgical and ablative treatment modalities for extramammary Paget's disease (EMPD) have high recurrence rates and can be associated with significant morbidity. OBJECTIVES: To evaluate photodynamic therapy (PDT) for the treatment of EMPD. METHODS: We conducted a retrospective review of notes and histology of five men with anogenital, groin and axillary EMPD treated with PDT at Roswell Park Cancer Institute between 20 April 1995 and 1 February 2001. RESULTS: Sixteen EMPD lesions were treated with topical aminolaevulinic acid (ALA)-PDT. Eleven of these lesions had failed previous Mohs micrographic surgery, excision or laser ablation. When evaluated 6 months after one treatment with ALA-PDT, eight of 16 (50%) sites achieved a complete clinical response (CR); six of eight CRs were in lesions that had failed prior conventional therapies. Three of the eight CRs (37.5%) recurred at 9, 10 and 10 months. One patient who was partially responsive to topical ALA-PDT subsequently received systemic Photofrin(R)-PDT, with a complete clinical and histological response at 1 year. Functional and cosmetic outcome was excellent in all patients. CONCLUSIONS: PDT is an effective treatment for EMPD. Recurrence rates are high with topical ALA-PDT, but comparable with standard therapies. Topical ALA-PDT causes little scarring and is preferred for superficial disease and mucosal surfaces. Systemic Photofrin(R)-PDT may be better suited for bulky disease. While further studies are indicated, PDT is well tolerated and appears to be a useful therapy for EMPD.
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Ácido Aminolevulínico/uso terapéutico , Enfermedad de Paget Extramamaria/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Anciano , Biopsia/métodos , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Paget Extramamaria/patología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Gastrointestinal stromal tumors (GIST) are rare tumors of the gastrointestinal (GI) tract that arise from primitive mesenchymal cells. GISTs occur throughout the GI tract but are usually located in the stomach and small intestine. The majority of GISTs are immunohistochemically positive for c-kit protein (CD 117) and CD34. GISTs express a heterogeneous clinical course not easily predicted by standard pathological means. The most important prognostic factors are size > 5 cm, tumor necrosis, infiltration and metastasis to other sites, mitotic count > 1-5 per 10 high-powered fields, and most recently, mutation in the c-kit gene. Surgical resection remains the mainstay of treatment, as chemotherapy and radiation are ineffective. Long-term follow-up is imperative, as recurrence rates are high.
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Neoplasias Gastrointestinales/patología , Leiomioma/patología , Leiomiosarcoma/patología , Neoplasias de Tejido Nervioso/patología , Árboles de Decisión , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/terapia , Humanos , Leiomioma/diagnóstico , Leiomioma/terapia , Leiomiosarcoma/diagnóstico , Leiomiosarcoma/terapia , Neoplasias de Tejido Nervioso/diagnóstico , Neoplasias de Tejido Nervioso/terapia , PronósticoRESUMEN
BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy with a high incidence of occult nodal metastases. MCC is believed to be similar in natural history to thick or ulcerated melanomas in its propensity for locoregional recurrence and early lymph node metastasis. Studies have shown that nodal status is statistically correlated to survival in MCC. Radiolocalization and superselective lymph node biopsy is a recent technique that has been proven to be of great value in evaluating the status of occult lymph node disease in malignant melanoma and breast cancer patients. OBJECTIVE: In previously untreated patients, an orderly progression of metastases is observed for both cutaneous carcinomas and malignant melanomas and is anticipated for MCC. METHODS/RESULTS. We present two patients with MCC of the head and neck who underwent simultaneous Mohs micrographic surgery and sentinel lymph node biopsy with intraoperative radiolocalization. CONCLUSION: Sentinel lymph node biopsy and intraoperative lymphoscintigraphy may prove to be a useful technique in evaluating occult nodal involvement and in limiting the potentially unnecessary morbidity of more comprehensive lymph node dissections in MCC patients who do not yet have metastatic involvement.
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Biopsia , Carcinoma de Células de Merkel/diagnóstico , Carcinoma de Células de Merkel/cirugía , Ganglios Linfáticos/patología , Cirugía de Mohs , Neoplasias Cutáneas/cirugía , Anciano , Carcinoma de Células de Merkel/secundario , Femenino , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Metástasis Linfática , Masculino , Cintigrafía , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/patologíaRESUMEN
Fungal infections causing deep tissue involvement are known as trichophytic granulomas. We describe an unusual case of trichophytic granuloma presenting in the vulva of a 39-year-old woman.
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Tiña/diagnóstico , Enfermedades de la Vulva/microbiología , Adulto , Diagnóstico Diferencial , Femenino , Granuloma/microbiología , Humanos , Tiña/patología , Enfermedades de la Vulva/patologíaRESUMEN
We report the results of studies undertaken to determine whether inhaled plant (i.e., cellulosic; e.g., cotton) and plastic (e.g., polyester) fibers are present in human lungs and, if so, whether inhaled fibers are also present in human lung cancers. Specimens of lung cancer of different histological types and adjacent nonneoplastic lung tissue were obtained from patients undergoing a lung resection for removal of a tumor. With the protection of a laminar flow hood and safeguards to prevent contamination by extraneous fibers, fresh, nonfixed, and nonstained samples of lung tissue were compressed between two glass microscope slides. Specimens in these dual slide chambers were examined with a microscope configured to permit viewing with white light, fluorescent light, polarizing light, and phase-contrast illumination. Near-term fetal bovine lungs and nonlung human tumors were used as controls. In contrast to the observations of these control tissues, morphologically heterogeneous fibers were seen repetitively in freshly excised human lung tissue using polarized light. Inhaled fibers were present in 83% of nonneoplastic lung specimens (n = 67/81) and in 97% of malignant lung specimens (n = 32/33). Thus, of the 114 human lung specimens examined, fibers were observed in 99 (87%). Examination of histopathology slides of lung tissue with polarized light confirmed the presence of inhaled cellulosic and plastic fibers. Of 160 surgical histopathology lung tissue slides, 17 were selected for critical examination; of these, fibers were identified in 13 slides. The inhalation of mineral (e.g., asbestos) fibers has been described by many investigators; we believe, however, that this is the first report of inhaled nonmineral (e.g., plant and plastic) fibers. These bioresistant and biopersistent cellulosic and plastic fibers are candidate agents contributing to the risk of lung cancer.
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Celulosa/análisis , Exposición por Inhalación/análisis , Pulmón/química , Plásticos/análisis , Adenocarcinoma/química , Adenocarcinoma/patología , Animales , Bovinos , Feto , Humanos , Exposición por Inhalación/efectos adversos , Pulmón/patología , Neoplasias Pulmonares/química , Neoplasias Pulmonares/patología , Microscopía Fluorescente , Microscopía de Contraste de Fase , Microscopía de Polarización , Fumar/metabolismo , Fumar/patologíaRESUMEN
BACKGROUND: Because medullary thyroid carcinoma accounts for only 7% of all thyroid malignancies, data to support treatment strategies are scarce. METHODS: We retrospectively reviewed treatment and outcome in 34 patients with MTC treated at Roswell Park between 1961 and 1995. Univariate analysis was performed using the variables age, sex, tumor size, N stage, and M stage. RESULTS: Median survival was 4.7 years, with 51% and 32% of patients alive at 5 and 15 years, respectively. Nodal metastases were seen in 76% and distant metastases in 67% of all patients. More than 60% of the patients with nodal metastases survived longer than 10 years. Once diagnosed with distant metastases, 90% of the patients died within 5 years. Local failure rate with lobectomy was 44%, compared to 10% after total thyroidectomy (P < .02). Age, extrathyroid extension, and M stage portend a poor outcome. Nodal status had no statistically significant impact on survival. CONCLUSION: Survival with tumors confined to the thyroid gland is independent of nodal status. Long-term survival in patients with distant metastases is rare. This study underscores the role of total thyroidectomy in the initial treatment and the need to develop effective adjuvant therapy for MTC.
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Carcinoma Medular/patología , Carcinoma Medular/terapia , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/terapia , Adolescente , Adulto , Anciano , Calcitonina/sangre , Carcinoma Medular/sangre , Niño , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Neoplasias de la Tiroides/sangre , TiroidectomíaRESUMEN
A palatal lesion was the initial manifestation of disseminated cryptococcosis in a patient with acquired immunodeficiency syndrome (AIDS). The diagnosis was initially verified with cytologic smears in situ and later confirmed with pathologic findings from an excisional biopsy specimen. As cryptococcosis is one of the major opportunistic infections in persons with AIDS, an increased incidence of oral manifestations of cryptococcosis can be expected.
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Síndrome de Inmunodeficiencia Adquirida/complicaciones , Criptococosis/patología , Enfermedades de la Boca/patología , Infecciones Oportunistas/patología , Adulto , Criptococosis/etiología , Diagnóstico Diferencial , Humanos , Masculino , Enfermedades de la Boca/etiología , Infecciones Oportunistas/etiología , Hueso Paladar/patologíaRESUMEN
The fetus can be considered an allograft with up to one-half of its MHC antigens being potentially recognized by the mother as foreign. This study compares expression of OKT3, OKT4, OKT8, Kappa, Lambda and Ia antigens on lymphocytes in the peripheral blood of normal non-pregnant women, normal pregnant women, patients who are chronic spontaneous aborters and pregnant insulin-dependent diabetic women. Monoclonal antibodies and cytofluorometric analyses were used for these determinations. There were no significant differences (P = 0.01) between these groups for T-cell markers. A statistically significant (P = 0.001) increased ratio of cells bearing surface immunoglobulin to those expressing Ia antigen (K&L/Ia) was observed between normal non-pregnant controls and women with a history of chronic spontaneous abortion. It is concluded that T-lymphocytes in the peripheral blood do not demonstrate a phenotypic abnormality that would account for the non-rejection of the fetal allograft; however, women with chronic spontaneous abortion may have abnormal B-cell differentiation or T-cell activation that mediates chronic spontaneous abortion.