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OBJECTIVES: Li-Fraumeni syndrome (LFS) is a cancer syndrome associated with early-onset neoplasias. The use of whole-body magnetic resonance imaging (WBMRI) is recommended for regular cancer screening, however, evidence supporting the benefits in asymptomatic LFS patients is limited. This study aims to assess the clinical utility of WBMRI in germline TP53 mutation carriers at baseline and follow-up. MATERIALS AND METHODS: We systematically searched PubMed, Cochrane, and Embase databases for studies evaluating WBMRI as an early detection method for tumor screening in patients with LFS. We pooled the prevalence of the included variables along with their corresponding 95% confidence intervals (CIs). Statistical analyses were performed using R software, version 4.3.1. RESULTS: From 1687 results, 11 comprising 703 patients (359 females (51%); with a median age of 32 years (IQR 1-74)) were included. An estimated detection rate of 31% (95% CI: 0.28, 0.34) for any suspicious lesions was found in asymptomatic TP53 carriers who underwent baseline WBMRI. A total of 277 lesions requiring clinical follow-up were identified in 215 patients. Cancer was confirmed in 46 lesions across 39 individuals. The estimated cancer diagnosis rate among suspicious lesions was 18% (95% CI: 0.13, 0.25). WBMRI detected 41 of the 46 cancers at an early-disease stage, with an overall detection rate of 6% (95% CI: 0.05, 0.08). The incidence rate was 2% per patient round of WBMRI (95% CI: 0.01, 0.04), including baseline and follow-up. CONCLUSION: This meta-analysis provides evidence that surveillance with WBMRI is effective in detecting cancers in asymptomatic patients with LFS. CLINICAL RELEVANCE STATEMENT: Our study demonstrates that whole-body MRI is an effective tool for early cancer detection in asymptomatic Li-Fraumeni Syndrome patients, highlighting its importance in surveillance protocols to improve diagnosis and treatment outcomes. KEY POINTS: Current evidence for whole-body MRI screening of asymptomatic Li-Fraumeni Syndrome (LFS) patients remains scarce. Whole-body MRI identified 41 out of 46 cancers at an early stage, achieving an overall detection rate of 6%. Whole-body MRI surveillance is a valuable method for detecting cancers in asymptomatic LFS patients.
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INTRODUCCIÓN. El gen Tp53 proporciona instrucciones para producir proteína tumoral 53. El Tp53 es un gen supresor tumoral que protege el ciclo celular, reparando el ADN o activando la apoptosis. Es clave en la carcinogénesis del carcinoma basocelular, patología que cobra relevancia en Ecuador, debido a su latitud y altitud, factores que determinan un mayor daño por exposición a radiación ultravioleta y por ende para carcinoma basocelular. Estudios sugieren que la inmunoexpresión de la proteína tumoral 53 podría ser un predictor de recurrencia en esta neoplasia. OBJETIVO. Determinar si el grado de expresividad de especies mutadas de proteína tumoral 53 en pacientes con carcinoma basocelular es una variable que tiene relación con la recurrencia y agresividad en los diferentes subtipos histológicos. MATERIALES Y MÉTODOS. Estudio de revisión bibliográfica de diferentes artículos científicos publicados en revistas indexadas y bases de datos durante los últimos diez años: ElSevier, Medigraphic, PubMed, Redalyc, ResearchGate, ScienceDirect, SpringerLink, Cochrane Database of Systematic Reviews. RESULTADOS. Se obtuvieron 104 resultados de los cuales se seleccionaron 50 artículos científicos que incluyeron revisiones sistemáticas, meta-análisis, artículos originales y reportes de casos en idiomas español e inglés. CONCLUSIÓN. Tp53 se encuentra mutado en más del 50% de carcinomas basocelulares y tiene un rol clave en su carcinogénesis. La inmunoexpresión aberrante de proteína tumoral 53 es un marcador de riesgo de recurrencia y agresividad en carcinoma basocelular, como lo indican los artículos revisados. Sin embargo, se requiere estudios locales que establezcan el verdadero valor de proteína tumoral 53 como marcador de recurrencia y/o agresividad en la población ecuatoriana.
INTRODUCTION. The Tp53 gene provides instructions to produce tumor protein 53. Tp53 is a tumor suppressor gene that protects the cell cycle, repairing DNA or activating apoptosis. It is key in the carcinogenesis of basal cell carcinoma, a pathology that is relevant in Ecuador, due to its latitude and altitude, factors that determine greater damage by exposure to ultraviolet radiation and therefore for basal cell carcinoma. Studies suggest that the immunoexpression of tumor protein 53 could be a predictor of recurrence in this neoplasm. OBJECTIVE. To determine whether the degree of expression of mutated species of tumor protein 53 in patients with basal cell carcinoma is a variable related to recurrence and aggressiveness in the different histologic subtypes. MATERIALS AND METHODS. Bibliographic review study of different scientific articles published in indexed journals and databases during the last ten years: El-Sevier, Medigraphic, PubMed, Redalyc, ResearchGate, ScienceDirect, SpringerLink, Cochrane Database of Systematic Reviews. RESULTS. A total of 104 results were obtained from which 50 scientific articles were selected, including systematic reviews, meta-analyses, original articles and case reports in Spanish and English. CONCLUSIONS. Tp53 is mutated in more than 50% of basal cell carcinomas and plays a key role in their carcinogenesis. Aberrant immunoexpression of tumor protein 53 is a risk marker for recurrence and aggressiveness in basal cell carcinoma, as indicated by the reviewed articles. However, local studies are required to establish the true value of tumor protein 53 as a marker of recurrence and/or aggressiveness in the Ecuadorian population.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Recidiva , Neoplasias Cutâneas , Imuno-Histoquímica , Carcinoma Basocelular , Proteína Supressora de Tumor p53 , Histologia , Apoptose , Equador , Ferroptose , NeoplasiasRESUMO
Acute erythroid leukemia (AEL) is an exceedingly uncommon but distinct hematological malignancy that shows neoplastic proliferation of erythroid precursors with maturation arrest and no significant myeloblasts. We describe an autopsy case of this rare entity in a 62-year-old man with co-morbidities. He underwent a bone marrow (BM) examination for pancytopenia during the first outpatient department visit, which revealed an increased number of erythroid precursors with dysmegakaryopoiesis suggesting the possibility of Myelodysplastic syndromes (MDS). Thereafter, his cytopenia got worsened, warranting blood and platelet transfusions. Four weeks later on the second BM examination, AEL was diagnosed based on morphology and immunophenotyping. Targeted resequencing for myeloid mutations revealed TP53 and DNMT3A mutations. He was initially managed along febrile neutropenia with the stepwise escalation of antibiotics. He developed hypoxia attributed to anemic heart failure. Subsequently, he had hypotension and respiratory fatigue pre-terminally and succumbed to his Illness. A complete autopsy showed infiltration of various organs by AEL and leukostasis. Besides, there was extramedullary hematopoiesis, arterionephrosclerosis, diabetic nephropathy (ISN-RPS class II), mixed dust pneumoconiosis, and pulmonary arteriopathy. The histomorphology of AEL was challenging, and the differential diagnoses were many. Thus, this case highlights the autopsy pathology of AEL, an uncommon entity with a strict definition, and its relevant differentials.
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ABSTRACT Acute erythroid leukemia (AEL) is an exceedingly uncommon but distinct hematological malignancy that shows neoplastic proliferation of erythroid precursors with maturation arrest and no significant myeloblasts. We describe an autopsy case of this rare entity in a 62-year-old man with co-morbidities. He underwent a bone marrow (BM) examination for pancytopenia during the first outpatient department visit, which revealed an increased number of erythroid precursors with dysmegakaryopoiesis suggesting the possibility of Myelodysplastic syndromes (MDS). Thereafter, his cytopenia got worsened, warranting blood and platelet transfusions. Four weeks later on the second BM examination, AEL was diagnosed based on morphology and immunophenotyping. Targeted resequencing for myeloid mutations revealed TP53 and DNMT3A mutations. He was initially managed along febrile neutropenia with the stepwise escalation of antibiotics. He developed hypoxia attributed to anemic heart failure. Subsequently, he had hypotension and respiratory fatigue pre-terminally and succumbed to his Illness. A complete autopsy showed infiltration of various organs by AEL and leukostasis. Besides, there was extramedullary hematopoiesis, arterionephrosclerosis, diabetic nephropathy (ISN-RPS class II), mixed dust pneumoconiosis, and pulmonary arteriopathy. The histomorphology of AEL was challenging, and the differential diagnoses were many. Thus, this case highlights the autopsy pathology of AEL, an uncommon entity with a strict definition, and its relevant differentials.
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The aim of this study was to investigate the immunohistochemical expression of REGγ, p53, MDM-2, Bcl-2, and Bax in oral tongue squamous cell carcinoma (OTSCC), and to correlate the findings with clinicopathological parameters. Fifty-eight OTSCC cases were selected for the study. The percentages of nuclear (REGγ, p53, and MDM-2) and cytoplasmic (Bcl-2 and Bax) staining in epithelial cells were determined and correlated with clinicopathological parameters (regional lymph node metastasis, clinical stage, clinical outcome, and histopathological grade of malignancy). Expression of REGγ was observed in all cases studied. Significantly lower percentages were observed in tumours with lymph node metastasis (P = 0.036) and in high-grade tumours (P = 0.013). No significant differences in p53, MDM-2, or Bax expression were observed according to the clinicopathological parameters. Lower percentages of Bcl-2 staining were found in high-grade OTSCC (P = 0.040) and in cases of disease-related death (P = 0.032). The expression of REGγ showed a weak positive correlation with the expression of MDM-2 (P = 0.001) and Bcl-2 (P = 0.014). The results of this study suggest that lower expression of REGγ may contribute to the progression of OTSCC. The role of REGγ in the development of OTSCC does not appear to be primarily related to the modulation of apoptosis in neoplastic cells.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias da Língua , Apoptose , Autoantígenos , Carcinoma de Células Escamosas/patologia , Humanos , Metástase Linfática , Complexo de Endopeptidases do Proteassoma , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias da Língua/patologia , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
Abstract: Tobacco smoking involves a high risk of human malignancies, including oral cancer, because it contains multiple carcinogens that cause genetic instability. Thus, a worse prognosis would be expected for cancer patients who are smokers. The aim of this study was to assess the DNA damage response through the expression of checkpoint kinase 2 (CHK2), H2A histone family member X (H2AX), and P53 among smokers and non-smokers with oral squamous cell carcinoma (OSCC). Associations between immunoexpression of proteins and clinicopathological data and histopathological grading were also analyzed. A total of 35 individuals (18 non-smokers and 17 smokers) with OSCC of the tongue and/or floor of the mouth were included. Immunohistochemistry for H2AX was conducted for the identification of double-strand breaks, CHK2, and P53 to evaluate the expression of this protein in cell cycle regulation. The sample consisted of 22 males and 13 females, with a mean age of 63.9±11.8 years. OSCC of non-smokers were well-differentiated tumors in 50% of the cases, and those of smokers were equally distributed into moderately differentiated and poorly differentiated tumors (35.3% each). Overall, 31 (88.6%) cases were CHK2-positive, 27 (77.1%) were H2AX-positive, and 23 (65.7%) were P53-positive, with no difference between smokers and non-smokers (p > 0.05). No association was found between proteins and clinicopathologic data (p > 0.05). Similarities in CHK2, H2AX, and P53 immunohistochemical staining patterns were observed between smokers and non-smokers, and immunoexpression was not associated with clinicopathological parameters. However, the findings indicated consistent expression of these proteins in OSCC.
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Oral squamous cell carcinoma (OSCC) is one of the most well-known malignancies that affect the human population worldwide. The early diagnosis and early intervention of OSCC help improve the survival rate of the patients. The tumour free surgical margins are a positive prognostic factor for recurrence-free survival. The molecular markers can be used to detect the tumour free surgical margins. Aim: The aim of the study is to evaluate the expression of p53 & Cyclin D1 marker in resected surgical apparently clear margins and to correlate the p53 & Cyclin D1 expression with clinicopathological characteristics and patient outcome. Methods: The study population included retrospective cases of OSCC with apparently clear margins (2017-18) n=10 and Clinicopathological variables relevant to survival analysis were recorded. Finally, two margins were selected from each case, a total of 20 margins were included in this study. Paraffin-embedded wax blocks retrieved and tissue sections were made. Expression of cyclin D1 and p 53 was assessed by the immunohistochemical staining procedure Results: Positive expressions Cyclin D1 in 40% of mild dysplasia margins and 60% in clearance adequate margins were present. p53 expression was seen in 16% of mild dysplasia margins and 84% in clearance adequate margins. The expression of p53 and Cyclin D1 molecular markers are noted in the basal & parabasal layer of epithelium. Conclusion: Molecular markers could play a more reliable method for the assessment of dysplasia at the margins
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Humanos , Masculino , Feminino , Carcinoma de Células Escamosas , Proteína Supressora de Tumor p53 , Ciclina D1RESUMO
INTRODUCTION: Actinic cheilitis (AC) is part of a spectral disease of keratinocyte carcinomas considered by some authors an early stage of in situ squamous cell carcinoma. Treatment options for AC can be lesion and field-directed therapies. Ingenol mebutate (IM) induces rapid and direct cell death and immune responses being able to destruct dysplastic cells. MATERIALS AND METHODS: This study enrolled patients with AC to receive IM gel 0.015% for self-application on the lower lip for 3 consecutive days. A biopsy was performed before and after treatment for histopathological and immunohistochemical evaluation. Local skin reactions (LSR) were evaluated. The level of significance considered was 5%. RESULTS: Fourteen patients were enrolled. All LSR had a complete resolution for up to 2 weeks. The most common adverse events were burning sensation, angular cheilitis, and pain. There was an improvement of more than 80% in patients' subjective evaluation. There was no statistically significant histopathological response since all patients remained with mild dysplasia. No reduction in the P53 expression was observed in the current study. CONCLUSIONS: Despite being a safe therapeutic method, the absence of histopathological or immunohistochemical response suggests that clinical improvement may not be accompanied by histopathological cure for AC treated with IM.
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Queilite , Diterpenos , Ceratose Actínica , Queilite/tratamento farmacológico , Diterpenos/uso terapêutico , Genes p53 , Humanos , Ceratose Actínica/tratamento farmacológico , Resultado do Tratamento , Proteína Supressora de Tumor p53RESUMO
The pathogenesis of megaloblastic hemopathies (MH) is centered on the deficiency of vitamin B12 and folic acid with interruption of erythrocyte maturation. This study researched the participation of p53 and p21 in the pathophysiology of the disease. A retrospective study enrolled 95 patients with histopathologic diagnosis by biopsy or bone marrow clot (BMB/BMC), with clinical review and immunohistochemical study in tissue microarray (TMA) for p53 and p21, detailing their marking location. All patients had BMC and only 11 had BMB. The CMO was a differential of this study and it allowed an expanded sample. In the TMA, 63.7% (58/91) of the samples were immunopositive for p53; and 35.2% (31/88) were immunopositive for p21. Nuclear staining, divergent from the literature, was observed in 17.3% (10/58) among those p53+ and in 38.7% (12/31) among those p21+. The pattern of immunostaining showed non-significant differences (P=0.474) regarding morphologic and clinical aspects. The positivity for both may indicate an effective balance between apoptosis and anti-apoptotic action. Excessive inhibition of apoptosis would contribute to high global cellularity, but without functional maturation effectiveness. In conclusion, there is p21 and/or p53 immunoexpression in most cases of this study and there is no clear association between immunoexpression pattern and patient outcome. Unlike the literature, we also found a percentage of nuclear immunostaining, but the finding was not statistically significant. Combination of p21 and p53 results created different possibilities of pathologic interpretation for MH, reinforcing the importance of studies similar to this one.
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ABSTRACT Background: Intestinal diversions have revolutionized the treatment of morbid obesity due to its viability and sustained response. However, experimental studies suggest, after these derivations, a higher risk of colon cancer. Aim: To analyze the histological and immunohistological changes that the jejunojejunal shunt can produce in the jejunum, ileum and ascending colon. Method: Twenty-four male Wistar rats were randomly divided into two groups, control (n=12) and experiment (n=12) and subdivided into groups of four. Nine weeks after the jejunojejunal shunt, segmental resection of the excluded jejunum, terminal ileum and ascending colon was performed. Histological analysis focused on the thickness of the mucosa, height of the villi, depth of the crypts and immunohistochemistry in the expression of Ki-67 and p53. Results: Significant differences were found between the experiment and control groups in relation to the thickness of the mucosa in the jejunum (p=0.011), in the ileum (p<0.001) and in the colon (p=0.027). There was also a significant difference in relation to the height of the villus in the ileum (p<0.001) and the depth of the crypts in the jejunum (p0.001). The results indicated that there is a significant difference between the groups regarding the expression of Ki-67 in the colon (p<0.001). No significant differences were found between the groups regarding the expression of Ki-67 in the jejunum and ileum. In the P53 evaluation, negative nuclear staining was found in all cases. Conclusion: The jejunojejunal deviation performed in the Roux-in-Y gastrojejunal bypass, predispose epithelial proliferative effects, causing an increase in the thickness of the mucosa, height of the villi and depth of the crypts of the jejunum, ileum and ascending colon.
RESUMO Racional: As derivações intestinais revolucionaram o tratamento da obesidade mórbida pela sua viabilidade e resposta sustentada. Porém, estudos experimentais sugerem, após estas derivações, risco maior de câncer de cólon. Objetivo: Analisar as alterações histológicas e imunoistológicas que a derivação jejunojejunal possa produzir no jejuno, íleo e cólon ascendente. Método: Foram utilizados 24 ratos Wistar machos randomicamente divididos em dois grupos, controle (n=12) e experimento (n=12) e subdivididos em grupos de quatro. Nove semanas após a derivação jejunojejunal procedeu-se a ressecção segmentar do jejuno excluso, íleo terminal e cólon ascendente. Análise histológica focou na espessura da mucosa, altura dos vilos, profundidade das criptas e a imunoistoquímica na expressão do Ki-67 e p53. Resultados: Foram encontradas diferenças significativas entre os grupos experimento e controle em relação à espessura da mucosa no jejuno (p=0,011), no íleo (p<0,001) e no cólon (p=0,027). Também houve diferença significativa em relação à altura dos vilos no íleo (p<0,001) e profundidade das criptas no jejuno (p<0,001). Os resultados indicaram que existe diferença significativa entre os grupos em relação à expressão do Ki-67 no cólon (p<0,001). Não foram encontradas diferenças significativas entre os grupos em relação à expressão do Ki-67 no jejuno e no íleo. Na avaliação do P53, foi encontrada coloração nuclear negativa em todos os casos. Conclusão: O desvio realizado na derivação gastrojejunal em Y-de-Roux, predispõem efeitos proliferativos epiteliais, causando aumento da espessura da mucosa, altura dos vilos e profundidade das criptas do jejuno, íleo e cólon ascendente.
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Humanos , Animais , Masculino , Ratos , Derivação Gástrica/efeitos adversos , Doenças do Colo/etiologia , Ratos Wistar , Antígeno Ki-67/metabolismo , Íleo , Mucosa Intestinal , Intestino Delgado , Intestinos , Jejuno/cirurgiaRESUMO
O câncer de boca corresponde a cerca de 4% das doenças neoplásicas, e o carcinoma de células escamosas representa o tipo mais frequente, englobando cerca de 90 a 95% dos casos. O cigarro é o principal fator etiológico para o câncer de boca, causando danos ao DNA e mutações que se não reparadas levam ao surgimento de lesões. O dano ao DNA associado ao cigarro tem sido estudado em diferentes tipos de câncer, mas ainda pouco explorado em relação ao câncer de boca. Checkpoint kinase 2 (CHK2) e P53 são proteínas que estão envolvidas no processo de checagem do ciclo celular, sendo responsáveis pelo reparo ao dano ao DNA. A proteína H2AX é uma histona nuclear que sofre fosforilação em resposta aos danos ao DNA, principalmente às quebras da dupla cadeia. O objetivo deste estudo foi avaliar a resposta a danos no DNA através da expressão de CHK2, γH2AX e TP53 entre fumantes e não fumantes com carcinoma de células escamosas de boca (CCEB). Além disso, foram analisadas associações entre imuno-expressão das proteínas estudadas, dados clínico-patológicos e classificação histopatológica. Foram incluídos 35 indivíduos (18 não fumantes e 17 fumantes) com CCEB de língua e soalho bucal. Reação imuno-histoquímica foi realizada para γH2AX para identificação de quebras de fita dupla, CHK2 e TP53 para avaliação da indução de parada do ciclo celular. Análises descritivas e estatísticas foram realizadas. A pesquisa foi composta por 22 homens (62,8%) e 13 mulheres (37,2%), com idade média de 63,9 anos. Entre os não fumantes, 50% apresentaram tumores bem diferenciados, enquanto que fumantes mostraram maior número em moderadamente diferenciados e pouco diferenciados (35,3% cada). No geral, 31 (88,6%) casos foram positivos para CHK2, 27 (77,2%) foram positivos para γH2AX e 23 (65,7%) foram positivos para TP53. Não foi observada associação entre essas proteínas com hábitos de fumar e não fumar (p> 0,05). Semelhanças entre os padrões imuno-histoquímicos de CHK2, γH2AX e TP53 em fumantes e não fumantes com CCEB foram observadas neste estudo, assim como entre os parâmetros clínico-patológicos. De forma geral, os resultados indicaram expressão positiva para essas proteínas no CCEB. Este estudo fornece informaçãoes sobre o dano ao DNA na carcinogênese oral.
Oral cancer accounts for about 4% of neoplastic diseases, and squamous cell carcinoma is the most common type, accounting for about 90 to 95% of cases. Cigarette smoking is the main etiological factor for oral cancer, causing DNA damage and mutations that, if not repaired, lead to lesions. Cigarette-associated DNA damage has been studied in different cancers, but is still poorly explored in relation to oral cancer. Checkpoint kinase 2 (CHK2) and P53 are proteins that are involved in the cell cycle checking process and are responsible for repairing DNA damage. The H2AX protein is a nuclear histone that undergoes phosphorylation in response to DNA damage, especially double strand breaks. The aim of this study was to assess the DNA damage response through the expression of checkpoint kinase 2 (CHK2), γH2A histone family member X (γH2AX) and TP53 among smokers and non-smokers with oral squamous cell carcinoma (OSCC). In addition, associations amongst immunoexpression of studied proteins, clinicopathologic data and histopathological grading were analyzed. Thirty-five individuals (18 nonsmokers and 17 smokers) with OSCC of the tongue and/or floor of the mouth were included. Immunohistochemistry was carried out for γH2AX for identification of double-strand breaks, CHK2 and P53 for evaluation of the induction of cell cycle arrest. Descriptive and statistical analyses were performed. The survey consisted of 22 males (62.8%) and 13 females (37.2%), with a mean age of 63.9 years. Fifty percent of non-smokers OSCC were well-differentiated tumors, whereas for smokers, OSCC were moderately differentiated and poorly differentiate tumors, equally (35.3% each). Overall, 31 (88.6%) cases were CHK2-positive, 27 (77.2%) were γH2AX-positive and 23 (65.7%) were TP53-positive. No association among these proteins with smoking and non-smoking habits was observed (p>0.05). Similarities in the CHK2, γH2AX and P53 immunohistochemical staining pattern were observed between smokers and non-smokers with OSCC in this survey, and the immunoexpression was not associated with clinicopathologic parameters. Overall, the results indicated consistent expression of these proteins in OSCC. This study provides information about the DNA damage in oral carcinogenesis.
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Nicotiana , Dano ao DNA , Neoplasias Bucais , Carcinoma de Células Escamosas , Proteína Supressora de Tumor p53 , Quinase do Ponto de Checagem 2 , Fumantes , não Fumantes , Estudos TransversaisRESUMO
ABSTRACT Objectives The aim of this study was to assess the possible role of HPV in the development of prostate cancer (PCa) and investigate the distribution of the p53 codon 72 polymorphism in PCa in a Turkish population. Materials and methods A total of 96 tissues, which had been obtained using a radical surgery method, formalin-fixed and parafin-embedded, were used in this study. The study group consisted of 60 PCa tissues (open radical prostatectomy) and the control group contained 36 benign prostatic hyperplasia tissues (BPH) (transvesical open prostatectomy). The presence of HPV and the p53 codon 72 polymorphism was investigated in both groups using real-time PCR and pyrosequencing. Results The results of the real-time PCR showed no HPV DNA in any of the 36 BPH tissue samples. HPV-DNA was positive in only 1 of the 60 PCa samples (1.7%). The HPV type of this sample was identified as HPV-57. The distribution of the three genotypes, Arg/Arg, Arg/Pro and Pro/Pro was found to be 45.6, 45.6, and 8.8% in the PCa group and 57.1%, 34.3% and 8.6% in the control group, respectively. Compared with the control group, patients with PCa had a higher frequency of the Arg/Pro genotype and Proline allele (odds ratio (OR)=1.67, 95% confidence interval (CI)=0.68-4.09, p=0.044; OR=1.13, 95% CI=0.76-1.68, p=0.021, respectively). Conclusions The results of the study do not support the hyphothesis that prostate cancer is associated with HPV infection but indicated that Proline allele can be a risk factor in the development of PCa in the Turkish population.
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Humanos , Masculino , Idoso , Idoso de 80 Anos ou mais , Papillomaviridae/isolamento & purificação , Polimorfismo Genético , Neoplasias da Próstata/genética , Neoplasias da Próstata/virologia , Proteína Supressora de Tumor p53/genética , Infecções por Papillomavirus/complicações , Prostatectomia , Hiperplasia Prostática/genética , Hiperplasia Prostática/patologia , Hiperplasia Prostática/virologia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Turquia , Códon/genética , DNA Viral , Prolina/genética , Estudos Retrospectivos , Fatores de Risco , Inclusão em Parafina , Estudos de Associação Genética , Gradação de Tumores , Técnicas de Genotipagem , Reação em Cadeia da Polimerase em Tempo Real , Genótipo , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: The aim of this study was to assess the possible role of HPV in the development of prostate cancer (PCa) and investigate the distribution of the p53 codon 72 polymorphism in PCa in a Turkish population. MATERIALS AND METHODS: A total of 96 tissues, which had been obtained using a radical surgery method, formalin-fixed and parafin-embedded, were used in this study. The study group consisted of 60 PCa tissues (open radical prostatectomy) and the control group contained 36 benign prostatic hyperplasia tissues (BPH) (transvesical open prostatectomy). The presence of HPV and the p53 codon 72 polymorphism was investigated in both groups using real-time PCR and pyrosequencing. RESULTS: The results of the real-time PCR showed no HPV DNA in any of the 36 BPH tissue samples. HPV-DNA was positive in only 1 of the 60 PCa samples (1.7%). The HPV type of this sample was identified as HPV-57. The distribution of the three genotypes, Arg/Arg, Arg/Pro and Pro/Pro was found to be 45.6, 45.6, and 8.8% in the PCa group and 57.1%, 34.3% and 8.6% in the control group, respectively. Compared with the control group, patients with PCa had a higher frequency of the Arg/Pro genotype and Proline allele (odds ratio (OR)=1.67, 95% confidence interval (CI)=0.68-4.09, p=0.044; OR=1.13, 95% CI=0.76-1.68, p=0.021, respectively). CONCLUSIONS: The results of the study do not support the hyphothesis that prostate cancer is associated with HPV infection but indicated that Proline allele can be a risk factor in the development of PCa in the Turkish population.
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Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Polimorfismo Genético , Neoplasias da Próstata/genética , Neoplasias da Próstata/virologia , Proteína Supressora de Tumor p53/genética , Idoso , Idoso de 80 Anos ou mais , Códon/genética , DNA Viral , Estudos de Associação Genética , Genótipo , Técnicas de Genotipagem , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Inclusão em Parafina , Prolina/genética , Prostatectomia , Hiperplasia Prostática/genética , Hiperplasia Prostática/patologia , Hiperplasia Prostática/virologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Fatores de Risco , TurquiaRESUMO
PURPOSE: The ability to measure oxidative DNA damage in a tissue allows establishment of the relationship between DNA damage and mutations in normal and neoplastic cells. It is well known that TP53 is a key inhibitor of tumor development and preserves the genome integrity in each cell. The aim of the present study was to investigate the relationship between DNA damage and TP53 mutation in colorectal adenoma and adenocarcinoma, and the value of DNA damage as potential marker of TP53 mutation in non-tumor tissues adjacent to colon malignant lesions. METHODS: Tissue samples were obtained by colonoscopy from patients with adenoma and/or adenocarcinoma and from healthy volunteers. Diagnosis was defined by histopathology. Immunohistochemistry with computer-assisted image analysis was performed to quantify TP53 mutation. Oxidative DNA damage was determined by comet assay. Statistical analyses were performed with 5 % of significance level. RESULTS: The TP53 level was higher in non-tumor tissues from tumor patients than in normal tissues from healthy volunteers (p = 0.01). Likewise, higher TP53 levels were observed in tumor tissues compared with the non-tumor tissues (p = 0.00). Oxidative DNA damage levels were higher in tumor tissues than in non-tumor tissues (p = 0.00). The amount of TP53 (p = 0.00) and oxidative DNA damage (p = 0.00) in normal and tumor tissue was related. The relationship between oxidative DNA damage and TP53 mutation was demonstrated in all samples (p = 0.00). CONCLUSION: Oxidative DNA damage is an intervening variable for TP53 mutation in colorectal adenoma-carcinoma. Our data suggests that oxidative DNA damage is a potential marker of TP53 mutation in colorectal carcinogenesis.
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Neoplasias Colorretais/genética , Dano ao DNA , Proteína Supressora de Tumor p53/genética , Neoplasias Colorretais/patologia , Feminino , Genes p53 , Humanos , Imuno-Histoquímica , Masculino , MutaçãoRESUMO
No existe un consenso sobre el manejo de las lesiones premalignas de laringe, en especial cuando se trata de displasias severas y carcinomas in situ. Por esto, se decidió evaluar el papel de los marcadores de inmunohistoquímica en displasias epiteliales, con el fin de definir su rol como factor de pronóstico durante el seguimiento. Se presenta una cohorte de pacientes mayores de 18 años, con diagnóstico de displasias laríngeas leves, moderadas y severas, con seguimiento mínimo de 6 meses. Se encontraron 4 pacientes con marcadores positivos con recidiva antes de los 6 meses, uno de ellos con malignización temprana. Un paciente adicional con recidiva y malignización 25 meses después del procedimiento inicial, 4 pacientes con marcadores positivos sin recidiva y un paciente con marcadores negativos sin recidiva. Tras más de 36 meses de seguimiento, se encontró una baja incidencia de displasias laríngeas, sin poder determinar la efectividad de los marcadores como factores pronósticos. Se analizan los datos como serie prospectiva, sentando una base para un estudio multicéntrico.
There is no consensus on the management of premalignant lesions of the larynx, especially when talking about severe dysplasia and carcinoma in situ. Therefore, we decided to evaluate the role of immunohistochemical markers as prognostic factors in epithelial dysplasia. A cohort of patients, 18 years old and older, diagnosed with mild, moderate and severe laryngeal dysplasia was followed since 2012 for up to at least 6 months. Four patients with positive markers had recurrence before 6 months of follow up, with one of them having an early malignancy. An additional patient had malignant recurrence identified 25 month after surgery. We found 4 markerpositive patients without recurrence, and one patient with negative markers with no recurrence. At 36 months follow-up, we found a low incidence of laryngeal dysplasia, therefore these results cannot rule out the effectiveness of immunohistochemical markers as prognostic factors for laryngeal dysplasia. The data are analyzed as a prospective series, laying the ground for an upcoming multicenter study.
Assuntos
Humanos , Leucoplasia , Neoplasias Laríngeas , Proteína Supressora de Tumor p53 , Antígeno Ki-67RESUMO
Objetivos Avaliar a correlação entre a expressão do Ki-67 e do p53 em astrocitomas graus II a IV, as características da RM e seu prognóstico. Métodos e Resultados Este é um estudo longitudinal retrospectivo do tipo coorte histórico que avaliou 45 pacientes. O prognóstico foi avaliado mediante revisão dos prontuários. A avaliação imuno-histoquímica foi realizada no Serviço de Patologia do HB. A avaliação das imagens de RMfoi feita no Serviço de Radiologia. A sobrevidamédia dos pacientes foi de 581,4 dias no grau IV; 1.704,8 dias no grau III; e 1.044,8 dias no grau II. Para cada grau, os seguintes percentuais de células positivas de Ki-67 e p53 tiveram respectivamente: 97,8 e 80% de positividade no grau IV; 72,7 e 73,4% de positividade no grau III; e 70 e 80% de positividade no grau II. Observou-se diferença estatística na expressão de Ki-67 entre os graus III e IV (P » 0,014). A RM mostrou especificidade de 64% e sensibilidade de 100% para a presença de necrose tumoral. Conclusão Concluímos que a análise da positividade do Ki-67 e do p53 não permite sua correlação com a sobrevida dos pacientes, apesar de ambos terem sua frequência distribuída de maneira semelhante. A RM tem especificidade moderada em relação ao exame patológico.rada em relação ao exame patológico.
Objectives To evaluate the correlation between the expression of Ki -67 and p53 in astrocytomas grades II to IV, the characteristics of MRI and its prognosis. Methods This was a retrospective longitudinal cohort study of its kind that evaluated 45 patients. Prognosis was assessed by review of medical records. The immunohistochemical evaluation was performed at the Pathology Service of HB. The evaluation of MRI images was taken in the Radiology Department. The median survival of patients was 581.4 days in grade IV; 1704.8 days in grade III; 1044.8 days in grade II. For each grade, the following percentages of cells positive for Ki -67 and p53 , respectively : 97.8% and 80% had a positive grade IV ; 72.7% and 73.4% positivity in grade III ; 70% and 80% in stage II positivity . There was statistical difference in Ki -67 between grades III and IV (P » 0.014).MRI showed 64% specificity and 100% sensitivity for the presence of tumor necrosis Conclusion We conclude that the analysis of the positivity of Ki -67 and p53 expression does not allow correlation with patient survival, although both their frequency distributed similarly. MRI hasmoderate specificity in relation to pathological examination.
Assuntos
Humanos , Masculino , Feminino , Astrocitoma/diagnóstico , Astrocitoma/imunologia , Proteína Supressora de Tumor p53 , Antígeno Ki-67 , Imageamento por Ressonância MagnéticaRESUMO
Meningiomas are common, usually benign tumors, with a high postoperative recurrence rate. However, the genesis and development of these tumors remain controversial. We aimed to investigate the presence and implications of a mutated p53 protein and dopamine D2 receptor in a representative series of meningiomas and to correlate these findings with age, gender, tumor grade, and recurrence. Tumor tissue samples of 157 patients diagnosed with meningioma (37 males and 120 females, mean age 53.6±14.3 years) who underwent surgical resection between 2003 and 2012 at our institution were immunohistochemically evaluated for the presence of p53 protein and dopamine D2 receptor and were followed-up to analyze tumor recurrence or regrowth. Tumors were classified as grades I (n=141, 89.8%), II (n=13, 8.3%), or grade III (n=3, 1.9%). Dopamine D2 receptor and p53 protein expression were positive in 93.6% and 49.7% of the cases, respectively. Neither of the markers showed significant expression differences among different tumor grades or recurrence or regrowth statuses. Our findings highlight the potential role of p53 protein in meningioma development and/or progression. The high positivity of dopamine D2 receptor observed in this study warrants further investigation of the therapeutic potential of dopamine agonists in the evolution of meningiomas.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Centros Médicos Acadêmicos , beta-Lactamases , Estudos de Casos e Controles , Estudos Transversais , Infecções por Enterobacteriaceae/etiologia , Enterobacteriaceae/genética , Enterobacteriaceae/isolamento & purificação , Escherichia coli/isolamento & purificação , Fezes/microbiologia , Gastroenteropatias , Klebsiella/isolamento & purificação , Assistência de Longa Duração , Prevalência , Pennsylvania/epidemiologia , Instituições Residenciais , Fatores de RiscoRESUMO
Purpose To compare dietary, lifestyle, clinical, anthropometric, genetic and prostatic features of Brazilian Indians and non-Indians (Amazon). Methods 315 men, 228 Indians and 89 non-Indians, ≥40 years old were submitted to digital rectal examination, serum prostate specific antigen (PSA), testosterone, TP53 and GSTP1 genotyping, anthropometric, lifestyle, dietary, personal and familial medical history. Prostatic symptoms were evaluated with the International Prostate Symptom Score (IPSS). Results Macuxis and Yanomamis represented 43.6% and 14.5% of Indians respectively who spontaneously referred no prostate symptoms. Mean IPSS was 7, range 3-19, with only 15% of moderate symptoms (score 8-19); Mean age was 54.7 years, waist circumference 86.6 cm, BMI 23.9 kg/m2. Yanomamis presented both lower BMI (21.4 versus 24.8 and 23.3, p=0,001) and prostate volume than Macuxis and “other ethnic groups” (15 versus 20, p=0.001). Testosterone (414 versus 502 and 512, p=0.207) and PSA (0.48 versus 0.6 and 0.41, p=0.349) were similar with progressive PSA increase with aging. Val/Val correlated with lower PSA (p=0.0361). Indians compared to control population presented: - TP53 super representation of Arg/Arg haplotype, 74.5% versus 42.5%, p<0.0001. -GSTP1 Ile/Ile 35.3% versus 60.9%; Ile/Val 45.9% versus 28.7%; Val/Val 18.8% versus 10.3%; p=0.0003. Conclusions Observed specific dietary, lifestyle, anthropometric and genetic profile for TP53 and GSTP1 may contribute to Brazilian Indian population prostate good health. .