Câncer colo-retal hereditário não polipose - Diagnóstico e surgimento de famílias de alto risco

Hereditary nonpolyposis colorectal cancer is an autosomal dominant condition caused by highly penetrant gene mutations. It is characterized by increased susceptibility for a specific group of cancer, mainly colorectal cancer. The syndrome originates from the inheritance of mutations in DNA mismatch repair genes. The most commonly affected genes in hereditary nonpolyposis colorectal cancer are hMLH1 and hMSH2. Their deficient expression renders the cell susceptible to the accumulation of many molecular defects, a condition which can be evaluated by the instability in sections of base repeats in the genoma known as microsatellite instability. The molecular detection of hereditary nonpolyposis colorectal cancer is possible in most of the highly suspicious cases. Genetic tests for hereditary nonpolyposis colorectal cancer also allow characterization of the individual that bears the mutation within a family. The high cost and restricted availability of these tests hamper their use for every person presenting colorectal cancer. Due to this fact, some clinical criteria have been developed by a hereditary nonpolyposis colorectal cancer international organization to select families with a high probability of carrying the mutation. Once families at risk are identified, they are encouraged to join a screening program that aims at early detection of hereditary nonpolyposis colorectal cancer-related cancers, increasing the possibility of its prevention and early detection.O câncer colo-retal hereditário não polipose é uma síndrome genética caracterizada por uma susceptilidade aumentada para certos tipos específicos de câncer, especialmente o câncer colo-retal. Ao nível molecular, a síndrome caracteriza-se pela herança autossômica dominante de mutações em genes envolvidos em um mecanismo de reparo do DNA dirigido para defeitos em trocas, ganhos ou perdas de um número de pequeno de bases, chamado de sistema de reparo de erros de pareamento. Os genes mais comumente afetados em câncer colo-retal hereditário não polipose são hMLH1 e hMSH2, e sua inativação destina a célula portadora à acumulação de mutações, uma condição conhecida como fenótipo de erro de replicação. Estas mutações múltiplas serão transmitidas e amplificadas em células-filhas e sua identificação pode ser feita por meio da identificação de distúrbios em seqüências repetidas de DNA chamadas de microssatélites. Células portadoras de defeitos deste tipo em seus microssatélites apresentam um fenótipo denominado de instabilidade de microssatélites (também denominado fenótipo MSI). Por meio da detecção destes defeitos genéticos é possível, presentemente, a realização de um diagnóstico preciso de câncer colo-retal hereditário não polipose, permitindo a atuação preventiva em portadores da síndrome que ainda não desenvolveram câncer. Contudo, limitações financeiras e de acesso aos exames inviabilizam sua realização em todos os indivíduos que apresentam câncer colo-retal. Por isso, foram estabelecidos pela comunidade internacional alguns critérios que selecionam as famílias com alta probabilidade de possuírem a mutação e que, portanto, podem beneficiar-se com estes exames. Este artigo procura abordar as estratégias recomendadas para identificação de casos de alto risco de câncer colo-retal hereditário não polipose, os testes genéticos disponíveis para estes casos e as recomendações para prevenção e seguimento destas famílias

Idade como fator prognóstico no câncer de mama em estádio inicial

OBJECTIVE: To analyze age as a prognostic factor in early breast cancer. METHODS: Retrospective study analyzing the clinical profile and disease-free survival in a group of 280 subjects aged 25 to 81 years with stage I and II breast cancer followed-up in Porto Alegre, southern Brazil, from 1995 to 2000. Clinical, pathological, treatment and outcome data were obtained from medical records. Subjects were divided into two groups according to age at diagnosis (;40 years). The two groups were compared for clinical stage, histology, hormone receptor expression, therapy and radiotherapy using the chi-square and/or Fisher's exact test and for analysis of survival the Kaplan-Meier method with a long-rank test. RESULTS: Of 280 women studied, 54 (19.3%) were younger than 40 years. Both groups were similar regarding clinical stage, histology, and hormone receptor expression. The proportion of subjects with disease-free survival in the 56-month follow-up was significantly higher in those over 40 years (84% versus 70%). Proportionally, younger subjects received more adjuvant therapy (88.8% vs. 77.8%). Those women over 40 years were significantly more likely to remain disease-free (84%), and this difference was more remarkable when they were compared to those over 40 years at stage I breast cancer. CONCLUSIONS: The study findings confirm that women younger than 40 years with early breast cancer have a poorer prognosis. However, this prognosis does not seem to be related to increased number of hormone receptor-negative cases. Younger patients who remained disease-free received more adjuvant therapy, suggesting a positive effect of chemotherapy and endocrine therapy.OBJETIVO: Analizar la edad como factor pronóstico en el cáncer de mama en fase clínico inicial. MÉTODOS: Estudio retrospectivo que analizó las características clínicas y la sobrevida libre de enfermedad de 280 pacientes entre 25 y 81 años con cáncer de mama fase clínica I y II con acompañamiento en hospital de Porto Alegre (Sur de Brasil), de 1995 a 2000. Datos clínicos, patológicos, tratamiento y resultados fueron extraídos de los prontuarios de las pacientes. Las pacientes fueron divididas en dos grupos conforme la edad al diagnóstico (;40 anos). Los dos grupos fueron comparados con relación a la fase clínica, histología, expresión de receptores hormonales, terapia y radioterapia utilizando la prueba chi-cuadrado y/o exacto de Fisher y para análisis de sobrevida, la prueba de long-rank y método de Kaplan-Meier. RESULTADOS: Del total de 280 mujeres estudiadas, 54 (19,3%) tenían hasta 40 años de edad. Ambos grupos de pacientes eran similares en fase clínica, histología y expresión de receptores hormonales. La proporción de pacientes con sobrevida libre de enfermedad en seguimiento de 56 meses fue significativamente mayor en las pacientes mayores de 40 años (84% vs. 70%). Proporcionalmente, las pacientes más jóvenes recibieron más terapia adyuvante (88,8% vs. 77,8%). Hubo diferencia significativa en la probabilidad de las mujeres mayores de 40 años de permanecer libre de enfermedad (84%), siendo más evidente cuando se compararon con las pacientes con < 40 años en fase clínica I. CONCLUSIONES: Los resultados confirman que mujeres de hasta 40 años con cáncer de mama inicial presentan un peor pronóstico. Sin embargo, tal pronóstico parece no estar relacionado con el mayor número de casos con receptores hormonales negativos. Pacientes jóvenes que permanecieron libres de enfermedad recibieron más terapia adyuvante, sugiriendo efecto positivo de la quimioterapia y hormonaterapia.OBJETIVO: Analisar a idade como fator prognóstico no câncer de mama em estádio clínico inicial. MÉTODOS: Estudo retrospectivo que analisou as características clínicas e a sobrevida livre de doença de 280 pacientes entre 25 e 81 anos com câncer de mama estágio clínico I e II com acompanhamento em hospital de Porto Alegre (RS), de 1995 a 2000. Dados clínicos, patológicos, tratamento e desfechos foram extraídos dos prontuários das pacientes. As pacientes foram divididas em dois grupos conforme a idade ao diagnóstico (;40 anos). Os dois grupos foram comparados quanto ao estágio clínico, histologia, expressão de receptores hormonais, terapia e radioterapia utilizando o teste qui-quadrado e/ou exato de Fisher e para análise de sobrevida, o teste de long-rank e método de Kaplan-Meier. RESULTADOS: Do total de 280 mulheres estudadas, 54 (19,3%) tinham até 40 anos de idade. Ambos os grupos de pacientes eram similares em estágio clínico, histologia e expressão de receptores hormonais. A proporção de pacientes com sobrevida livre de doença em seguimento de 56 meses foi significativamente maior nas pacientes acima de 40 anos (84% versus 70%). Proporcionalmente, as pacientes mais jovens receberam mais terapia adjuvante (88,8% versus 77,8%). Houve diferença significativa na probabilidade das mulheres acima de 40 anos de permanecerem livre de doença (84%), sendo mais evidente quando comparadas às pacientes com < 40 anos em estágio clínico I. CONCLUSÕES: Os achados confirmam que mulheres de até 40 anos com câncer de mama inicial apresentam um pior prognóstico. Entretanto, tal prognóstico parece não estar relacionado a maior número de casos com receptores hormonais negativos. Pacientes jovens que permaneceram livre de doença receberam mais terapia adjuvante, sugerindo efeito positivo da quimioterapia e hormonioterapia

Prostasin, A Potential Tumor Marker in Ovarian Cancer- A Pilot Study

INTRODUCTION: Ovarian cancer is generally diagnosed at advanced stages of the disease; therefore, poor prognoses are typical. The development of tumor markers is thus of utmost importance. Prostasin is a protease that in normal tissues is highly expressed only in the prostate gland and seminal fluid. A previous study showed that prostasin is highly overexpressed in ovarian cancer cell lines. This study sought to evaluate the expression of prostasin in ovarian cancer. METHODS: Fresh tumor samples of ovarian epithelial cancer (n: 12) were analyzed for expression of prostasin mRNA (messenger ribonucleic acid) by conventional and real time quantitative PCR (polymerase chain reaction). As a standard control, a normal prostate sample was analyzed. RESULTS: Using conventional PCR, prostasin was detected in all but one sample. Using quantitative PCR, prostasin was over-expressed in all but one of the samples as compared to the control (prostate). CONCLUSIONS: These findings indicate that prostasin is overexpressed in many epithelial ovarian cancers. Further studies of prostasin as a potential biomarker for this disease are warranted

Report of a case of anaplastic large cell lymphoma associated with a breast implant in a Brazilian patient

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a T-cell lymphoproliferative disorder that has recently been recognized as an independent entity in the World Health Organization (WHO) classification of lymphomas. Despite the small number of reports to date, the number of cases is rapidly increasing. Of the few hundred cases that have been reported so far, very few came from Brazil and none have been reported to the local authorities. We encountered a case of BIA-ALCL and believe that its report to the local plastic surgery community could raise awareness to this emerging pathology. The prognosis is very good in most of the diagnosed cases. However, little is known about how and why silicone implants could trigger a lymphoid response that results in ALCL

Should extragonadal germ cell tumors be included in studies of families with testicular germ cell tumors?

Abstract\ud \ud \ud \ud Background\ud \ud Family history is among the few established risk factors for testicular germ cell tumor (TGCT). Approximately 1.4% of newly diagnosed TGCT patients report a positive family history of TGCT. Sons and siblings of TGCT patients have four- to six fold and eight- to tenfold increase in TGCT risk, respectively. In twins of men with TGCT the relative risk of testicular cancer is 37.5 (12.3-115.6). Nevertheless, information about the occurrence of TGCT in relatives of patients with extragonadal germ cell tumor is limited.\ud \ud \ud \ud Case report\ud \ud A 24 year-old male patient was diagnosed with a mediastinum tumor and was submitted to image-guided biopsy, which revealed a seminoma. Two months later, his non-identical asymptomatic twin brother was submitted to an elective ultrasound of the testes, which showed a left testicular mass of 4.2 cm. This patient underwent orchiectomy revealing a seminoma of the left testis. There are no other cases of seminoma or other types of cancers reported in first-degree relatives in this family.\ud \ud \ud \ud Conclusions\ud \ud Although familial aggregations of TGCT have been well described, to the best of our knowledge, no data concerning the association of gonadal and extragonadal germ cell tumor in relatives has been previously reported. Further investigation on this association is warranted and may help in improving our knowledge of familial pattern inheritance.We thank the patients and their family, without whose cooperation this report would not have been possible

The germline mutational landscape of BRCA1 and BRCA2 in Brazil

The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-six novel variants were reported from both genes, and BRCA2 showed higher mutational heterogeneity. Some recurrent mutations were reported exclusively in certain geographic regions, suggesting a founder effect. Our findings confirm that there is significant molecular heterogeneity in these genes among Brazilian carriers, while also suggesting that this heterogeneity precludes the use of screening protocols that include recurrent mutation testing only. This is the first study to show that profiles of recurrent mutations may be unique to different Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be effective.This work was supported in part by grants from Barretos Cancer Hospital (FINEP - CT-INFRA, 02/2010), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 2013/24633-2 and 2103/23277-8), Fundação de Apoio à Pesquisa do Rio Grande do Norte (FAPERN), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Ministério da Saúde, the Breast Cancer Research Foundation (Avon grant #02-2013-044) and National Institute of Health/National Cancer Institute (grant #RC4 CA153828-01) for the Clinical Cancer Genomics Community Research Network. Support in part was provided by grants from Fundo de Incentivo a Pesquisa e Eventos (FIPE) from Hospital de Clínicas de Porto Alegre, by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, BioComputacional 3381/2013, Rede de Pesquisa em Genômica Populacional Humana), Secretaria da Saúde do Estado da Bahia (SESAB), Laboratório de Imunologia e Biologia Molecular (UFBA), INCT pra Controle do Câncer and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). RMR and PAP are recipients of CNPq Productivity Grants, and Bárbara Alemar received a grant from the same agencyinfo:eu-repo/semantics/publishedVersio