Abstract Background: Breast apocrine carcinoma (BAC) and cutaneous apocrine carcinoma (CAC) are both adenocarcinomas with apocrine morphology. BAC is a mammary epithelial adenocarcinoma with apocrine metaplasia, whereas CAC arises from cutaneous apocrine glands. The axilla is not only rich in apocrine glands but can also contain ectopic breast tissue, allowing both tumors to arise. Despite different treatments and prognoses, they share highly similar histologic features, and no reliable diagnostic markers exist. We hypothesized that transcriptomic analyses could clarify the biological differences between BAC and CAC and provide molecular insights for distinguishing them. Methods: We utilized clinical and transcriptomic data from the ORIEN cohort (breast carcinoma, n = 1,797 including 4 BACs; skin cancers, n = 331 including 2 CACs) and YCU (BAC, n = 5; CAC, n = 2). We compared BAC and CAC in terms of clinicopathologic features, gene expression profiles, and pathway analyses. In addition, we developed a diagnostic score based on differentially expressed genes (DEGs) between the two tumor types. Results: In both the ORIEN and YCU cohorts, CAC showed worse recurrence and survival outcomes than BAC. In transcriptomic analyses, CAC demonstrated significant upregulation of Hallmark pathways related to cell proliferation such as E2F targets, G2M checkpoint and MYC targets v1/v2, and the expression level of Ki67, a proliferation marker gene, was also higher in CAC, although this was not statistically significant. Pathways related to immune responses were also upregulated in CAC; however, infiltration levels of individual immune cell types showed no clear differences between the two groups. We compared the expression of genes corresponding to ten immunohistochemical markers previously reported to distinguish BAC from CAC (positive in BAC: adipophilin, GATA3, mammaglobin, calretinin; positive in CAC: CK5/6, podoplanin, p63, CD14, CK17, and PAX5). CK5/6 and podoplanin showed higher expression in CAC in both cohorts, which was consistent with previous reports, although the differences did not reach statistical significance . The remaining markers showed either no consistent differences between cohorts or exhibited patterns inconsistent with previous reports. We then developed a score to distinguish BAC from CAC using the ORIEN cohort. To create this score, we first built a LASSO regression model using DEGs that separated all breast cancers from all skin cancers, then added a second component based on DEGs between BAC and CAC. By combining these two DEG-based components, we generated the distinguishing score. Validation using the YCU cohort demonstrated 100% sensitivity and specificity, accurately distinguishing BAC from CAC. Conclusions: CAC exhibited higher cell proliferative activity and poorer prognosis compared with BAC. The transcriptomic score accurately distinguished BAC from CAC. Citation Format: Kei Kawashima, Eleanor A. Fallon, Kohei Chida, Mahato Sasamoto, Masanori Oshi, Akimitsu Yamada, Itaru Endo, Kazuaki Takabe. Molecular biological differences between breast and cutaneous apocrine carcinomas abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6530.
Kawashima et al. (Fri,) studied this question.