Perfil molecular dos carcinomas ductais in situ de alto grau da mama puros ou associados a carcinoma invasor. Detecção por imunofenotipagem molecular.

Abstract

Introduction: Recent studies using cDNA microarrays identified distinct groups of tumours, with different prognosis, and developed a new classification of breast carcinomas based on molecular profile. Many studies evaluated invasive breast carcinomas, but few studies evaluated the molecular profile of ductal carcinomas in situ of the breast based on immunohistochemistry. Purpose: To evaluate the frequency of different molecular profiles in a series of cases of high grade ductal carcinomas in situ of the breast, pure or associated to invasive carcinoma; to compare the frequency of molecular profiles in components in situ and invasive; to verify the agreement of molecular profiles between both components in cases containing in situ associated to invasive components. Material and methods: One hundred and twenty-one cases of high grade ductal breast carcinomas in situ, pure or associated to invasive carcinoma assessed at the Hospital das Clínicas from Federal University of Minas Gerais from 2003 to 2008. The immunohistochemical assessment included estrogen receptor (ER) and progesterone receptor (PR), HER2 overexpression (HER2), cytokeratins 5 (CK5) and 14 (CK14) and expression of the epidermal growth factor receptor (EGFR/ HER1). The tumours were classified in five subgroups according the molecular classification: luminal A (ER+/HER2-/CK5-), luminal B (ER+/HER2+/CK5-), HER2 (ER-/HER2+/CK5-), basal (CK5+, regardless of others markers); not classified (all markers negative). Results: Among pure ductal carcinomas in situ, the phenotype more frequent was luminal A (24/42 cases; 57.1%), afterwards the HER2 and not classified phenotypes (6/42 cases; 14.3% for both), luminal B (5/42 cases; 11.9%) and basal phenotype (1/42 cases; 2.4%). Among ductal carcinomas in situ associated to invasive carcinomas, the luminal A phenotype also was more frequent (44/79 cases; 55.7% and 50/77 cases; 64.9% respective to carcinoma in situ and invasive). The HER2 phenotype corresponded to 6/79 cases (7.6%) in ductal carcinoma in situ and 4/77 cases (5.2%) in invasive carcinoma. Basal phenotype was observed in 10/79 cases (12.7%) in carcinoma in situ and 5/77 cases (6.5%) in invasive component. There was no significant difference among the frequencies of different molecular phenotypes in pure ductal carcinoma in situ or associated to invasive component (p > 0.05). Basal phenotype showed tendency to higher positivity in ductal carcinoma in situ associated to invasive component (p = 0,095). Excellent agreement among different molecular phenotypes in both components in situ and invasive was observed (kappa = 0,823). Conclusions: Our results showed similar frequency distributions of molecular phenotypes of ductal carcinoma in situ of the breast were observed in previous studies. Our results showed good agreement between ductal carcinomas in situ andsynchronic invasive carcinomas with relation to different molecular phenotypes