Relationship between androgen receptor and androgen receptor-related protein expression in breast cancers focusing on morphologically identified carcinoma with apocrine differentiation

Sep 23, 2026

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Breast cancer subtyping relies on biomarker expression, yet apocrine differentiation—carcinoma with apocrine differentiation (CAD)—is defined morphologically and lacks comprehensive profiling of androgen receptor (AR)–related proteins. Using immunohistochemistry on 66 invasive ductal carcinomas, 21 invasive lobular carcinomas, and 27 CAD cases, the study assessed AR and multiple AR-related proteins and compared patterns across subtypes. CAD showed universal AR positivity and high expression of selected AR-linked markers, including nuclear p-mTOR with strong specificity, and proposed combinations that may support diagnosis and androgen-related targeted therapy research.

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Results

AR and AR-related protein expression in breast cancer

Expression of AR-related proteins in AR-positive cases

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Relationship between androgen receptor and androgen receptorrelated protein expression in breast cancers focusing on morphologically identified carcinoma with apocrine differentiation Haruto Nishida􀀍, Ami Kato, Ryo Kaimori, Kazuhiro Kawamura & Tsutomu Daa Breast cancer (BC) is classified based on the expression of histopathological markers, namely, estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) . Carcinomas with apocrine differentiation (CAD) are classified based on morphology. Androgen receptor (AR) is highly expressed inCAD; however, no study has comprehensively examined AR-related proteins inCAD. Therefore, we examined the expression ofAR-related proteins andAR, compared protein expression patterns between morphologically identified CAD and other BC subtypes, and investigated CAD characteristics. We performed immunohistochemistry forAR and various AR-related proteins in 66 invasive ductal carcinoma (32 ER+/PgR+/HER2−, 8 ER+/PgR+/HER2+, 12 ER−/PgR−/HER2+, and 14 ER−/PgR−/HER2− [triple-negative breast cancer)), 21 invasive lobular carcinoma, and 27 CAD cases. In the CAD group, all cases wereAR-positive; some AR-related proteins were highly expressed. Nuclear phosphorylated-mammalian target of rapamycin was highly expressed inCAD cases compared with that in other BC groups, with a 33.3% sensitivity and 97.7% specificity. AR-expressing CAD cases exhibited high expression of other AR-related proteins. Specifically, the combination ofAR+, GCDFP15+, and ER − or AR+, FOXA1+, and ER −may be useful for the diagnosis and treatment of AR-positive BC and CAD. These results may assist in androgen-related molecular targeted therapy research. Keywords Breast cancer, Androgen receptor, Molecular targeted therapy, Apocrine differentiation In women, the incidence of breast cancer (BC) is the highest among all cancers in several countries (159/185 countries); furthermore, BC accounts for the highest cancer-related mortality in 110 of 185 countries1. BC treatment is dictated by histological type and biomarker status2. It is pathologically classified into four molecular subtypes, namely, luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, or basallike (triple-negative), based on the expression of biomarkers, such as estrogen receptor α (ER), progesterone receptor (PgR), HER2, and Ki67, as determined using immunohistochemistry (IHC)3. Although this classification is widely used in clinical settings for hormone therapy and chemotherapy, some BCs exhibit apocrine differentiation, and carcinoma with apocrine differentiation (CAD) (formerly apocrine carcinoma; AC) is defined based on the morphology as per the World Health Organization (WHO) classification of breast tumors (5th edition)4. CAD is histologically distinguished by large cells with abundant eosinophilic granular cytoplasm and enlarged nuclei with prominent nucleoli, with some cases showing apocrine decapitation4. The expression of androgen receptor (AR) or gross cystic disease fluid protein-15 (GCDFP15) is also used to diagnose CAD supportively3–5. Department of Diagnostic Pathology, Faculty of Medicine, Oita University, 1-1, Idaigaoka, Hasamamachi, Oita 879- 5593, Oita, Japan. 􀀍 email: [nharuto@oita-u.ac.jp](nharuto@oita-u.ac.jp) [www. nature.com/scientificreports/](www. nature.com/scientificreports/) Although the expression of ARs has been studied in different molecular subtypes, these molecules have not been comprehensively examined in BC6. Therefore, in the present study, we aimed to identify the characteristic biomarkers of morphologically identified CAD through comparison with other subtypes of BC and propose anew method for the diagnosis of CAD, which could in turn guide treatment. Results AR andAR-related protein expression in BC The IHC results for AR or AR-related protein expression in CAD and n

FAQs

How was carcinoma with apocrine differentiation (CAD) defined in the study?

CAD was classified based on morphology showing apocrine differentiation, and AR-related marker expression was evaluated supportively.

Which AR-related proteins showed high sensitivity in CAD cases?

AR and FOXA1 showed the highest sensitivity, while GCDFP15, p-mTOR, SOX9, and TRPS1 also demonstrated relatively high sensitivity.

What was the diagnostic performance of nuclear phosphorylated-mammalian target of rapamycin (p-mTOR) for CAD?

Nuclear p-mTOR was significantly associated with CAD, with high specificity and lower sensitivity compared with other groups.

Sep 23, 2026

Uploaded by Finn