Male Breast Cancer—Immunohistochemical Patterns and Clinical Relevance of FASN, ATF3, and Collagen IV

Abstract

Background: Male breast carcinoma (male BC) is an uncommon neoplasia without individualized strategies for diagnosis and therapeutics. Low overall survival (OS) rates have been reported, mostly associated with patients’ advanced stage and older age. Intratumoral heterogeneity versus homogeneity of malignant epithelial cells seems to be an important factor to consider for the development of combination therapies with curative intention. Objective: In this preliminary study, we aim to provide valuable insight into the distinct clinicopathologic features of male BC. Material and methods: In a series of 40 male BC patients, we evaluated by immunohistochemistry androgen receptor; activating transcription factor 3 (ATF3); p16; cyclin D1; fatty acid synthase (FASN); fatty acid transport protein 1 (FATP1); β1, β3, β4, and β6 integrins; collagen I and collagen IV; and their interactions. Kaplan-Meier survival curves and log-rank tests were assessed for statistical analysis. Results: Homogeneous epithelial staining of p16, ATF3, β6 integrin, FASN, and FATP1 was found to be significantly intercorrelated, and associated with high Ki67. These markers also stained tumor stromal fibroblasts. The prognostic analysis showed statistically significant associations of FASN with disease-free survival (DFS) and OS, as well as of ATF3 with OS and collagen IV with DFS. Conclusions: This study highlights, as a novel finding, the relevance of FASN, ATF3, and collagen IV immunophenotypes, which may have innovative application in the clinical management of male BC.

Clinicopathological features, genetic alterations, and BRCA1 promoter methylation in Japanese male patients with breast cancer

“…Like patients in Western countries, Japanese patients with MBC exhibited a high rate of HR positivity. The rate of AR positivity was significant and higher than that reported in previous studies [ 21 , 26 ]. In contrast, most Japanese patients with MBC did not express PD-L1 (93.2%).…”

“…It is possible that methylation of the BRCA1 promoter region does not contribute to carcinogenesis in Japanese patients with MBC; however, due to the small number of samples analyzed in this study, we cannot draw such a conclusion with certainty. Methylation of RAD51B and XRCC3 has been reported to contribute to carcinogenesis [ 26 ] and should be the subject of further investigation.…”