Fibrotic focus and hypoxia in male breast cancer

Fibrotic focus is a scar-like lesion near the center of a carcinoma and has been associated with high-grade, lymph node metastases and poor survival in female breast cancers. Hypoxia is suggested to be the crucial link between fibrotic focus and aggressive tumor phenotype and is also itself a poor prognostic marker. We here set out to study fibrotic focus and hypoxia in male breast cancer for the first time. In a group of 134 male breast cancer patients, the presence and size of a fibrotic focus and the expression of three hypoxia-related immunohistochemical stainings, hypoxia-inducible factor-1a, carbonic anhydrase IX and Glut-1 were studied in correlation with clinicopathological features and prognosis. Fibrotic focus was seen in 25% of the male breast cancer cases and was correlated with hypoxia-inducible factor-1a overexpression (P ¼0.023), high grade (P ¼0.005), high mitotic activity (P ¼0.005) and lymph node metastases (P ¼0.037). Hypoxia-inducible factor-1apositive tumors were more often high grade (P ¼0.003) and HER2 amplified (P ¼0.005). Glut-1 expression was also more common in grade 3 tumors (P ¼0.038), but no association between carbonic anhydrase IX and any clinicopathological feature was found. Fibrotic focus 48mm and hypoxia-inducible factor-1a overexpression were correlated with decreased patients’ outcome (P ¼0.035 and 0.008, respectively). Hypoxia-inducible factor1a overexpression was an independent and the most powerful predictor of survival in multivariate analysis (P ¼0.029; hazard ratio 2.5). In conclusion, the presence of a fibrotic focus is associated with hypoxia-inducible factor-1a overexpression, and both are associated with aggressive tumor phenotype and poor survival in male breast cancer. These markers seem to have similar clinical importance as previously reported in female breast cancer. Modern Pathology (2012) 25, 1397–1404; doi:10.1038/modpathol.2012.101; published online 8 June 2012