C-kit immnunohistochemical expression in breast carcinomas and lymph node metastasis. Lack of prognostical significance and review of literaturei

Objective: To evaluate the expression of c-kit in breast invasive ductal carcinomas (IDC) and metastasis to lymph nodes considering epithelial and stromal components separately and correlate this variable to others clinical, pathological and biological markers (EGFR, Her-2, ER, PR, Ki-67 and p53 expression). Methods: We analysed 80 IDC, stage T2-T4 Nx Mx, in TMA of epithelial, stromal component and lymph nodes. Statistical analysis considered significant a p value < 5%. Results: c-kit expression was founded in 9 cases in epithelial component (11.3%) and in 10 cases (12.5%) of stromal component. The 43 samples of lymph nodes metastasis were negative. EGFR and Her-2 were predominantly negative, both in epithelial (77.5% and 73.75%, respectively), as stromal (97.5% and 95.0%) components and metastasis to lymph nodes (83.7% and 62.8%). While ER, PR, Ki-67 and p53 were positive in 49 (61.0%), 40 (53.0%), 67 (83.75%) and 59 cases (73.75%) in the epithelial component. Stromal cells have proved negatives. c-kit epithelial expression correlated to presence of in situ component (p = 0.044) and stromal c-kit expression correlated to presence of necrosis (p = 0.002). There was no association between c-kit expression and staging and biological markers. Transformed epithelial cells at me lymph nodes metastasis stained for ER, PR, Ki-67 and p53 in 27 (62.8%), 16 (37.5%), 41 (95.0%) and 28 cases (65.1%), respectively. Conclusions: The expression of c-kit is mostly negative in primary IDC both in the epithelial and stromal component, as well as in lymph node metastasis. The lack of correlation between c-kit and others tyrosine kinase proteins suggest that they are independently regulated. Metastasis for Iymph nodes were not c-kit positive and further studies of mutations of c-kit and his family, correlate with other prognostic factors and survival required to reveal the exact mechanism of action of this molecule in breast cancer.

Objetivo: Avaliar a expressão de c-kit em células epiteliais, estromais e metástases para linfonodos de carcinomas ductais mamários invasivos (CDI) e correlacionar essa variável com os outros marcadores clínicos, patológicos e biológicos (EGFR, HER-2, RE, RP, Ki-67 e p53). Métodos: Analisaram-se 80 CDI, estádios T2-T4 Nx Mx, em TMA de componente epitelial, estromal e linfonodos. O valor de p < 5% foi considerado significante. Resultados: A expressão de c-kit foi encontrada em 9 casos no componente epitelial (11,3%) e em 10 casos (12,5%) do componente estromal. As 43 amostras de metástases para linfonodos foram negativas. EGFR e Her-2 foram predominantemente negativos, tanto em epitélio (77,5% e 73,75%, respectivamente), como estroma (97,5% e 95,0%) e metástases para linfonodos (83,7% e 62,8%), enquanto RE, RP, Ki-67 e p53 foram positivos em 49 (61,0%), 40 (53,0%), 67 (83,75%) e 59 casos (73,75%) no componente epitelial. Células do estroma se mostraram negativas. A expressão de c-kit epitelial correlacionou-se com a presença do componente in situ (p = 0,044) e a expressão de c-kit no estroma se associou com a presença de necrose (p = 0,002). Não houve associação entre a expressão de c-kit com estadiamento e marcadores biológicos. Células epiteliais transformadas de metástases para linfonodos coraram para RE, RP, Ki-67 e p53 em 27 (62,8%), 16 (37,5%),41 (95,0%) e 28 casos (65,1%), respectivamente. Conclusões: A expressão de c-kit é majoritariamente negativa em CDI primário tanto no componente epitelial quanto no estromal, assim como em metástases linfonodais. A falta de correlação entre o c-kit e outras proteínas tirosina quinases sugere que elas sejam reguladas de forma independente. Metástases para linfonodos não foram positivas para c-kit, e estudos posteriores de mutações do c-kit e sua família, correlacionando com outros fatores prognósticos e sobrevida, são necessários para revelar o exato mecanismo de ação dessa molécula no câncer de mama.

Expression and Mutational Analysis of c-kit in Ovarian Surface Epithelial Tumors

Coexpression of Kit ligand and c-kit has been reported in some gynecologic tumors. To determine whether imatinib mesylate is useful in ovarian epithelial tumors, we performed immunohistochemical and mutational analysis. The cases consisted of 33 cases, which included 13 serous cystadenocarcinomas, 1 borderline serous tumor, 8 mucinous cystadenocarcinomas, 6 borderline mucinous tumors and 5 clear cell carcinomas. Five cases of serous cystadenoma and 5 cases of mucinous cystadenoma were also included. In the immunohistochemical study, 3 cases (3/6, 50%) of borderline mucinous cystic tumor and two cases (2/8, 25%) of mucinous cystadenocarcinoma show positive staining for KIT protein. Only one case (1/13, 7.7%) of serous cystadenocarcinoma had positive staining. On mutational analysis, no mutation was identified at exon 11. However, two cases of borderline mucinous tumors and one case of mucinous cystadenocarcinoma had mutations at exon 17. In these cases, the immunohistochemistry also shows focal positive staining at epithelial component. Although, KIT protein expression showed higher incidence in mucinous tumors than serous tumors, they lack KIT-activating mutations in exon 11. Thus, ovarian surface epithelial tumors are unlikely to respond to imatinib mesylate.