A genética molecular de sarcomas de partes moles e sua aplicação à clínica / The molecular genetics of soft tissue sarcomas and its clinical application

Sarcomas de partes moles, como outros tumores humanos, são causados por mutações em genes supressores de tumores e oncogenes. Entre eles alguns, como p53 por exemplo, são freqüentemente detectados na forma mutatada em sarcomas e outros tumores humanos. De outro lado, há várias mutações altamente específicas para determinados sarcomas que podem servir como marcadores diagnósticos de alto valor. Exemplos de mutações de potencial diagnóstico incluem a translocação entre PAX3 e FKHR em rabdomiossarcoma alveolar, a translocação entre EWS e FLI-1 em tumores neuroectodérmicos periféricos primitivos e EWS e ATF-1 e sarcomas de células claras. Todas essas translocações podem ser detectadas por metodologias moleculares e que podem constituir um componente importante de repertório diagnóstico futuro.

Aspectos fisiopatológicos da disseminação de sarcomas / Aspects of physiopathology of sarcoma dissemination

Ao longo do processo tumoral, algumas células evadem mecanismos de vigilância intra e extracelular. Essas células adquirem a capacidade de invadir tecidos e colonizar órgãos a distância caracterizando os processos de invasão e metastatização, que caracterizam o câncer. Aqui, revisamos alguns dos elementos que caracterizam o processo de disseminação tumoral, comparando sarcomas, carcinomas e melanomas. Ressaltamos a participação de elementos celulares normais do hospedeiro como moduladores do processo de invasão tumoral. Diferentemente de células tumorais, geralmente heterogêneas e geneticamente menos estáveis, as células do hospedeiro que modulam o processo de disseminação são geneticamente estáveis e fenotipicamente homogêneas. Discutimos a necessidade de se modificar o alvo de estratégias antitumorais, centrado na célula tumoral, ampliando-o para incluir os elementos celulares normais (vasos neoformados) e elementos do sistema imune-agentes moduladores da progressão tumoral.

Li-fraumeni syndrome in pediatric patients with soft tissue sarcoma or osteosarcoma

Family history of cancer and features of the Li-Fraumeni syndrome (LFS) were investigated in 42 patients with soft tissue sarcoma or osteosarcoma in a pediatric hospital in Mexico City, and compared with 42 non-cancer children. Six subjects with cancer were found among 204 first-degree relatives of cancer patients while there were none among 183 first-degree relatives of non-cancer children. In three families, the proband had two affected relatives, and the type of neoplasia as well as the age of onset suggested the clinical diagnosis of LFS. Our results show that 7.1 percent of our pediatric patients with soft tissue sarcoma or osteosarcoma may belong to LFS families. The authors encourage pediatric and adult oncologist to pay more attention to the history of cancer in nuclear families for eventual hereditary cancer syndrome identification and cancer prevention

Argyrophilic nucleolar organizer regions in soft tissue tumors.

Argyrophilic nucleolar organizer region (AgNOR) staining was employed on 51 apparently normal representative soft tissues, 53 benign soft tissues tumors and 52 malignant soft tissue tumors with an aim to study the sensitivity and specificity of method in differentiating between the benign and malignant soft tissue tumors. The mean AgNORs count in apparently normal fibrous tissue was 1.02, whereas it was 0.94 in adipose tissue, 1.14 in smooth muscle tissue, 1.115 in skeletal muscle tissue, 1.025 in blood vessels endothelial lining cells and 1.04 in nerve tissue. The mean AgNOR count was found to be higher in benign soft tissue tumors as compared to respective apparently normal soft tissue and was found to be statistically significant. The mean AgNOR count in soft tissue sarcomas was found to be higher as compared to both apparently normal soft tissue and benign soft tissue tumors. An increase AgNOR score in both benign and malignant soft tissue tumors as compared to apparently normal soft tissue indicates high proliferative activity. The neurofibrosarcoma showed low AgNOR count as compared to other soft tissues sarcomas. The fibrohistiocytic sarcoma, leiomyosarcoma and angiosarcoma showed a mean AgNOR score of 4 or more than four. The mean AgNOR score was found to increase with high grade of the tumor. The AgNOR staining is simple and useful method in estimating tumor cell proliferation thereby differentiating normal soft tissue from non-neoplastic proliferative growth, benign and malignant soft tissue tumors. It may help in differentiating fibromatosis from fibrosarcoma, dermatofibrosarcoma protuberans of low grade malignancy from high grade malignant fibrous histiocytoma and benign hemangiopericytoma from malignant hemangiopericytoma.

Flow cytometric analysis of DNA ploidy in childhood rhabdomyosarcoma

Flow cytometric DNA analysis was performed on 17 rhabdomyosarcomas in conjunction with a histopathological review to determine the usefulness of this technique to predict the biologic behavior of the tumor and to establish the characteristic ploidy pattern of rhabdomyosarcoma compared to other small round cell tumors occurring in childhood. Aneuploidy including near-tetraploidy is the most common ploidy pattern encountered, followed by multiploidy and diploidy, and the presence of multiploidy in this tumor is useful for differentiating rhabdomyosarcoma from other kinds of small round cell tumors in which there are rare previous reports on occurrence of multiploidy. Even though there is no significant correlation between ploidy pattern and histologic type of rhabdomyosarcoma, patients with multiploid tumors or aneuploid tumors with a DNA index of 1.10-1.80 tend to have a high risk of treatment failure. Therefore, the ploidy pattern seems to be useful for predicting the patient's survival in concert with other variables.

Cancer mortality in relatives of desmoid sarcoma patients

Pacientes menores de 16 anos, com diagnóstico de sarcoma do tipo desmóide atendidos no Hospital M.D. Anderson da Universidade do Texas pelo período de 1944 e 1975, foram revistos. A mortalidade esperada foi calculada aplicando-se as taxas de mortalidade específicas por idade, raça e sexo dos Estados Unidos sobre a mortalidade pessoa/ano de risco observado. A razäo da mortalidade padronizada - SMR - foi computada. Para o conjunto dos 429 parentes dos 26 casos de sarcoma do tipo desmóide aqui analisados, näo foi encontrado excesso de mortes, observado/esperado= 13/24.7. O risco dos pais terem câncer também näo foi significativo, observado/esperado= 2/1.83. Esses resultados säo indicativos de que as taxas de mortalidade por esse tipo de tumor, tanto para este grupo particular de famílias como para a populaçäo em geral, näo säo os parâmetros adequados para estudar fatores hereditários e ocorrência de tumores desmóides. Sugere-se a comparaçäo de taxas de incidência de tumores benignos em tecidos moles entre os membros da família dos casos com as taxas destes mesmos tumores na populaçäo em geral.