Molecular subtyping of mammary-like adenocarcinoma of the vulva shows molecular similarity to breast carcinomas.

AIMS: Mammary-like adenocarcinoma (MLA) of the vulva is thought to be derived from vulvar mammary-like glands. The aim of this study was to characterize a series of MLAs by using an immunohistochemical algorithm that identifies the major molecular subtypes of breast cancer. METHODS AND RESULTS: Seven cases of vulval MLA were stained for oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki67, epidermal growth factor receptor (EGFR), cytokeratin (CK) 5, nestin, and inositol polyphosphate-4-phosphatase (INPP4b). Seventeen cases of vulval extramammary Paget disease (EMPD), seven with invasion, were studied for comparison. The median age of patients with MLA was 72 years. All tumours except one were early-stage tumours. On the basis of an immunohistochemical panel, three of seven tumours were classified as luminal B, two of seven as HER2-enriched, one of seven as luminal A, and one of seven as basal-like. ER was expressed in four of seven tumours, PR in three of seven, HER2 in three of seven, EGFR in two of seven, and CK5 in one of seven, and the Ki67 index was >15% in six of seven cases. Nestin and INPP4b were, respectively, negative and positive in all cases. Of the seven cases of invasive EMPD, two showed a luminal A profile, three a luminal B profile (two of three with HER2 amplification), one a HER2-enriched profile, and one a basal-like profile. Three of seven were HER2-amplified. Among the 10 cases of EMPD without invasion, seven showed a luminal A profile and three showed a luminal B profile (all HER2-amplified); no HER2-enriched or basal-like subtypes were identified. CONCLUSIONS: Breast cancer subtyping can be applied to vulvar MLAs. All four intrinsic molecular subtypes are seen, with frequencies similar to those in breast carcinoma. Our results support the potential use of breast cancer molecular profiling algorithms to guide treatment for these cancers.