Aims The aim of this study was to determine the role of hypoxia in male breast carcinogenesis by evaluating the expression of the hypoxia-related proteins, hypoxia-inducible factor-1α (HIF-1α), carbonic anhydrase IX (CAIX) and glucose transporter-1 (Glut-1), in ductal carcinoma in situ (DCIS) of the male breast in relation to invasive cancer (IC).
Methods Tumour tissue blocks of 18 cases of pure DCIS, 58 DCIS cases adjacent to IC (DCIS-AIC) and the 58 IC cases were stained by immunohistochemistry for HIF-1α, CAIX and Glut-1, and expression frequencies and patterns (diffuse and/or perinecrotic) were noted.
Results HIF-1α overexpression was observed in 61.1% (11/18) of pure DCIS, in 37.9% (22/58) of DCIS-AIC and in 36.2% (21/58) of IC cases (not significant (n.s.)). CAIX overexpression was observed in 16.7% (3/18) of pure DCIS, in 37.9% (22/58) of DCIS-AIC and in 24.1% (14/58) of IC cases (n.s.). Glut-1 overexpression was observed in 61.1% (11/18) of pure DCIS, in 75.9% (44/58) of DCIS-AIC and in 62.1% (36/58) of IC cases (n.s.). Expression of hypoxia-related proteins was seen around necrosis in a little over one-third of DCIS cases, and often coincided with expression in adjacent IC when present. All these observations indicate that the hypoxia response is already at its maximum in the preinvasive DCIS stage.
Conclusions In conclusion, male DCIS frequently shows activated hypoxia response, comparable to male IC. This indicates that the activated hypoxia response previously seen in male IC is not a late bystander but likely a genuine carcinogenetic event.
- ductal carcinoma in situ
- breast cancer
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Handling editor Cheok Soon Lee.
Contributors MV contributed to the study concept, design, data collection, histopathological analysis and writing. CvD, CS and JM contributed to the patient and data collection, and reviewed and edited the manuscript. PvD contributed to the study concept, design, histopathological analysis, and edited and reviewed the manuscript. All the authors gave the final approval.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval Archival tissue of all patients was handled according to the Dutch Code for Proper Use of Human Tissue (www.federa.org).
Provenance and peer review Not commissioned; externally peer reviewed.