Aspectos histopatológicos e imunofenotípicos do carcinoma ductal in situ da mama puro e associado a carcinoma invasor

Abstract

Introduction: Ductal carcinoma in situ (DCIS) of the breast is an inherent but not necessarily obligate tendency for progression to invasive breast cancer. The pathogenesis and evolutive aspects of DCIS are still not completely elucidated. A better morphological and molecular evaluation of DCIS would be useful for clinical decision making. The aims of this study were to determine clinical and morphological features, the immunophenotypes of a series of cases of DCIS and to evaluate the agreement about the histopathological diagnosis of intraductal proliferative breast lesions. Methods: This is a retrospective, observational, cross-sectional study. Four hundred and three cases of DCIS, pure or associated with invasive carcinoma, were consecutively identified from the histopathology files of the Breast Pathology Laboratory, School of Medicine, Federal University of Minas Gerais, Brazil, from 2003 to 2008. Immunohistochemistry was performed in 121 highgrade DCIS cases. Estrogen receptor (ER), progesterone receptor (PR), receptor of epidermal growth factor receptor 2 (HER2), cytokeratin 5 (CK5), receptor of epidermal growth factor receptor 1 (EGRF), cyclooxygenase-2 (COX-2), tumor suppressor protein p16 and nuclear antigen Ki67 were assessed. Tumors were placed into five subgroups according to their immunophenotypical profile: luminal A (ER+/HER2-), luminal B (ER+/HER2+), HER2 (ER-/HER2+), basal-like (ER-/HER2-/EGFR+ and/or CK5+), and not classified (all markers negative). Results: The high nuclear grade and the presence of comedonecrosis were identified more frequently in DCIS of younger patients and more often correlated with the solid pattern DCIS (p<0.05). A moderate agreement was observed in the diagnosis of the intraductal proliferative breast lesions, especially atypical ductal hyperplasia, DCIS and DCIS with microinvasion. The most common immunophenotype of pure DCIS was luminal A, followed by HER2 phenotype. The basal-like phenotype was observed only in DCIS associated with invasive carcinoma that had a similar phenotype. No significant difference was identified between pure DCIS and IMC-associated DCIS phenotypes. We observed that p16 expression, isolated or in combination with Ki67 and COX-2, is associated with basal phenotype in high-grade DCIS. Conclusions: A significant discrepancy in the diagnosis of intraductal proliferative breast lesions was observed in our series. The most common type of DCIS was the luminal A. The basal phenotype was less frequent and only seen when associated with basal-type invasive carcinoma. DCIS of high nuclear grade, with comedonecrosis were more often found in younger patients and these characteristics should be considered in the surgical treatment decision. P16 expression, p16+/Ki67+/COX2+ and p16+/Ki67+/COX2- co-expressions showed significant association with basal phenotype and they could be useful to guide more aggressive treatments in patients with high-grade DCIS.