Carcinoma de la mama triple negativo aspectos morfológicos y expresión de CK 5/6 / Triple negative breast cancer morphological aspects and CK 5/6 expression

El carcinoma mamario es una enfermedad heterogénea, parámetros de clasificación, factores pronósticos, no siempre predicen su curso clínico. La genética molecular, los ha estratificado en grupos diferentes a la clasificación morfológica. Trabajos respaldan que un grupo específico: carcinoma de “tipo basal” tiene peor pronóstico, es frecuentemente triple negativo, es decir: RE(-), RP(-), C-erbB-2(-) expresa citoqueratinas de epitelios basales, como la citoqueratina 5/6 (CK5/6, planteamos determinar los aspectos morfológicos de estos carcinomas, identificar la frecuencia en la que expresan CK5/6 por inmunohistoquímica, relacionarlos con parámetros clínicos disponibles. Se seleccionaron 91 carcinomas entre 2003-2008 se les realizó CK5/6. 34 (37,4 por ciento) fueron TN-CK5/6(+) y 57 (62,6 por ciento) fueron TN-CK5/6(-). Las características morfológicas descritas se observaron en ambos grupos, más frecuentemente en los carcinomas TN-CK5/6(+). La detección de estos tumores por inmunohistoquímica es una forma práctica, rentable de identificar a este grupo de peor pronóstico en la práctica diaria.

Breast cancer is heterogeneous disease classification parameters prognostic factors are not always predictors its clinical course. Molecular genetics are categorizing in different ways, as the well-known morphologic classification. Studies endorse specific group within this classifying system: Basal-like carcinomas, has worst prognosis; tends to be triple-negative: ER(-), RP(-), Erb-B2(-); expresses basal cytokeratins, such as cytokeratin 5/6 (CK5/6). Considered determining morphological aspects, frequency in which they express CK5/6 through immunohistochemistry, and contrasting them to existing clinical parameters. 91 carcinomas were selected between the years 2003-2008 and checked for CK5/6. Or the aforementioned cases, 34 (37.4 percent) resulted TN-CK5/6(+) and 57(62.6 percent) resulted TN-CK5/6(-). Morphological aspects described for and carcinomas were observed in both groups, though they were more frequent in breast carcinomas TN-CK5/6(+). For this reason, detecting these tumors using immunohistochemistry is a practical, worthwhile, and convenient way to identify this group with the worst prognosis on our daily routines.

Molecular characterization of breast cancer in young Brazilian women / Caracterização molecular do câncer de mama e mulheres brasileiras jovens

OBJECTIVE: To evaluate the distribution of molecular subtypes of breast tumors diagnosed in young Brazilian women and to analyze the frequency of loss of heterozygocity (LOH) in BRCA1 among different molecular subtypes of early-onset breast cancer. METHODS: Samples from 72 cases of invasive breast carcinoma diagnosed in women aged between 19 and 40 years were evaluated using an immunohistochemical panel of biomarkers. Three intragenic BRCA1 locus microsatellites, D17S1322, D17S1323, and D17S855, were PCR amplified from matched normal (lymphocyte) and tumor DNAs for (LOH) analysis. RESULTS: We found 13 cases (18 percent) that had an immunohistochemical profile consistent with being basal-like. Forty cases (55 percent) were luminal A type; 11 percent (8 cases) were luminal B type, 13 percent (9 cases) were HER2-overexpressing tumors and two cases were ER-/HER2- carcinomas lacking basal marker expression. Four of the 16 informative cases at D17S1322, one of the four informative cases at D17S855, and none of the five informative cases at D17S1323 displayed LOH (four basal-like and one Luminal A). Microsatellite instability (MSI) at D17S855 and D17S1322 was found in two cases (one a basal-like and one Luminal A). CONCLUSION: In our study, basal-like tumor was the second most frequent molecular type among young Brazilian women and was only observed in women diagnosed under the age of 35 years. There was no significant difference of LOH at BRCA1 locus rates between basal-like breast tumors and not-basal-like breast tumors (p=0.62). LOH in BRCA1 and MSI in these breast cancers were not frequent but may indicate a small group of breast cancers with a specific molecular makeup.

OBJETIVO: Avaliar a distribuição dos subtipos moleculares dos tumores de mama diagnosticados em mulheres brasileiras jovens e determinar a frequência de perda de heterozigose (LOH) no gene BRCA1 entre os diferentes subtipos moleculares de tumores. MÉTODOS: Setenta e dois casos de carcinoma invasivo de mama diagnosticados em mulheres entre 19 e 40 anos de idade foram classificados de acordo com o subtipo molecular utilizando um painel imunoistoquímico e para a análise de LOH foram utilizados três marcadores intragênicos para o gene BRCA1 (D17S1322, D17S855, D17S1323). RESULTADOS: Treze casos (18 por cento) apresentaram perfil imunoistoquímico compatível com carcinoma do tipo basal (basal-like tumor). Quarenta casos (55 por cento) foram classificados como tumores do tipo luminal A; 11 por cento (oito casos) do tipo luminal B, 13 por cento (nove casos) corresponderam a tumores com superexpressão de HER2 (HER2-overexpressing tumors) e dois casos corresponderam a carcinomas ER/HER2 negativos sem expressão de marcadores basais. LOH foi detectada em quatro dos 16 casos informativos para o marcador D17S1322 e em um dos quatro casos informativos para D17S855. Instabilidade de microssatélites (MSI) foi observada em dois casos, um do tipo basalóide e um do tipo luminal A. CONCLUSÃO: Carcinomas do tipo "basal-like" corresponderam ao segundo subtipo molecular mais frequente entre os tumores de mama diagnosticados neste grupo de mulheres e foram restritos às mulheres com idade inferior a 35 anos. Não houve diferença significativa na frequência de LOH no gene BRCA1 entre os subtipos moleculares (p= 0,62). A frequência de LOH e de instabilidade de microssatélite em BRCA1 foi baixa neste grupo de pacientes, porém podem indicar um pequeno grupo de cânceres de mama com características moleculares específicas distintas.

Radiotherapeutic implications of genetic instability of tumor cells

A mathematical model was used to explore the radiotherapeutic implications of genetic instability. The model included two populations whose different radiosensitivity was represented by different values of alpha parameter of linear quadratic model. It was shown that the presence of a small fraction of mutants may profoundly affect an optimal treatment schedule structure, especially for radiosensitive tumors currently deemed suitable for treatment by hyperfractionation. In some cases, the analysis favors hypofractionation or hybrid schedules composed of hyperfractionated and hypofractionated phases