AMACR Expression is a Potential Diagnostic Marker in Apocrine Lesions of Breast, and is Associated with High Histologic Grade and Lymph Node Metastases in Some Invasive Apocrine Breast Cancers
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
36577560
DOI
10.1016/j.clbc.2022.11.012
PII: S1526-8209(22)00268-3
Knihovny.cz E-resources
- Keywords
- AMACR, Alpha-methylacyl CoA racemase, Apocrine breast cancer, Breast Pathology, Immunohistochemistry,
- MeSH
- Humans MeSH
- Neoplasm Recurrence, Local MeSH
- Lymphatic Metastasis MeSH
- Biomarkers, Tumor metabolism MeSH
- Breast Neoplasms * metabolism MeSH
- Racemases and Epimerases MeSH
- Receptor, ErbB-2 metabolism MeSH
- Receptors, Estrogen metabolism MeSH
- Receptors, Progesterone metabolism MeSH
- Triple Negative Breast Neoplasms * diagnosis MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Biomarkers, Tumor MeSH
- Racemases and Epimerases MeSH
- Receptor, ErbB-2 MeSH
- Receptors, Estrogen MeSH
- Receptors, Progesterone MeSH
BACKGROUND: Carcinoma with apocrine differentiation (AC) is a subtype of breast carcinoma with apocrine features in >90% of the tumor. Molecular studies demonstrate AC has high expression of androgen receptor (AR) mRNA. Pure AC lack estrogen receptor (ER), progesterone receptor (PR), and express AR, with variable human epidermal growth factor 2 (HER2) status. Currently, in triple negative AC, no targetable therapies or specific diagnostic markers exist. MATERIALS AND METHODS: α-Methylacyl CoA racemase (AMACR) expression was investigated as a marker of apocrine differentiation using a single-plex immunoperoxidase stain, and a novel AMACR/p63 dual stain in a subset of cases, across 1) benign apocrine lesions (apocrine metaplasia, adenosis) 2) apocrine DCIS (ADCIS), 3) AC/ invasive ductal carcinoma (IDC) with apocrine features, 4) non-apocrine triple negative breast cancer (TNBC) and 5) IDC, no special type. A sub-set of cases were evaluated by tissue microarray. RESULTS: AMACR expression was increased in both AC and ADCIS, with minimal expression in benign breast tissue, TNBC and IDC, NST cases. In invasive cases, those with positive AMACR (>5% positivity) were significantly associated with higher histologic grade (P = .006), initial N stage (chi squared 0.044), and lack of ER or PR expression (both P < .001), with no correlation with overall survival. Analysis of TCGA breast cancer datasets revealed AMACR expression was significantly higher in molecularly defined apocrine carcinomas relative to basal and luminal subtypes. Moreover, high AMACR expression predicted worse relapse-free and distant-metastasis free survival, among both ER-/PR-/Her2- and ER-/PR-/Her2+ breast cancer cohorts (log-rank P = .081 and .00011, respectively). CONCLUSION: AMACR represents a promising diagnostic and prognostic marker in apocrine breast lesions. Further study is needed to determine the biologic and clinical significance of this protein in AC.
BIOCEV Charles University Vestec Czech Republic
Department of Surgery Section of Surgical Oncology Yale University School of Medicine New Haven CT
Department of Surgical Pathology Yale University School of Medicine New Haven CT
Yale Pathology Tissue Services Yale University School of Medicine New Haven CT
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