title: Molecular subtyping of male breast cancer by immunohistochemistry.
abstract: Molecular subtyping of breast cancer by gene expression has proven its significance in females. Immunohistochemical surrogates have been used for this classification, because gene expression profiling is not yet routinely feasible. Male breast cancer is rare and large series are lacking. In this study, we used immunohistochemistry for molecular subtyping of male breast cancer. A total of 134 cases of male breast cancer were immunohistochemically stained on tissue microarrays for estrogen receptor (ER), progesterone receptor (PR), HER2 and epidermal growth factor receptor (EGFR), as well as for CK5/6, CK14, and Ki67. HER2 was also assessed by chromogen in situ hybridization. Cases were classified as luminal A (ER+ and/or PR+, and HER2- and Ki67 low), luminal B (ER+ and/or PR+, and HER2+ or Ki67 high), HER2 driven (ER-, PR-, HER2+), basal-like (ER-, PR-, HER2-, CK5/6+ and/or CK14+ and/or EGFR+), or unclassifiable triple-negative (negative for all six markers). Luminal type A was by far the most encountered type of male breast cancers, representing 75% of the cases. Luminal type B was seen in 21% and the remaining 4% of cases were classified as basal-like (n=4) and unclassifiable triple-negative (n=1). No HER2 driven cases were identified. Patients with basal-like cancer were significantly younger (P=0.034). Luminal B type cancers showed significantly higher histological grade (P<0.001), mitotic index (P<0.001), and PR negativity (P=0.005) compared with luminal type A cancers. In conclusion, most male breast cancers are luminal A and luminal B types, whereas basal-like, unclassifiable triple-negative, and HER2 driven male breast cancers are rare. Luminal type B seem to represent a subtype with an aggressive phenotype. This distribution of molecular subtypes in male breast cancer is clearly different compared with female breast cancers, pointing to possible important differences in carcinogenesis.
authors: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Robert
authors: R
authors: Kornegoor
authors: Anoek H J
authors: AH
authors: Verschuur-Maes
authors: Horst
authors: H
authors: Buerger
authors: Marieke C H
authors: MC
authors: Hogenes
authors: Peter C
authors: PC
authors: de Bruin
authors: Joost J
authors: JJ
authors: Oudejans
authors: Petra
authors: P
authors: van der Groep
authors: Bernd
authors: B
authors: Hinrichs
authors: Paul J
authors: PJ
authors: van Diest
mesh_terms: D000230:Adenocarcinoma / Q000145:classification* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D018567:Breast Neoplasms, Male / Q000145:classification* / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007633:Keratins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D040081:Protein Array Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D007633:Keratins; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011987:Receptors, Steroid; C508053:ERBB2 protein, human