EGFR and HER-2/neu expression in invasive apocrine carcinoma of the breast

Abstract

This study was undertaken to investigate epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER-2)/neu expression in a cohort of apocrine carcinomas of the breast with emphasis on the classification of the breast tumors with apocrine morphology. In total, 55 breast carcinomas morphologically diagnosed as apocrine were evaluated for the steroid receptor expression profile characteristic of normal apocrine epithelium (androgen receptor positive/estrogen receptor (ER) negative/progesterone receptor (PR) negative), and for the expression of EGFR and Her-2/neu proteins, and the copy number ratios of the genes EGFR/CEP7 and HER-2/CEP17. On the basis of the results of steroid receptors expression, 38 (69%) cases were classified as pure apocrine carcinoma (androgen receptor positive/ER negative/PR negative), whereas 17 (31%) were re-classified as apocrine-like carcinomas because they did not have the characteristic steroid receptor expression profile. Her-2/neu overexpression was observed in 54% of the cases (57% pure apocrine carcinomas vs 47% apocrine-like carcinomas). HER-2/neu gene amplification was demonstrated in 52% of all cases (54% pure apocrine carcinomas vs 46% apocrine-like carcinomas). EGFR protein (scores 1 to 3 þ ) was detected in 62% of all cases and was expressed in a higher proportion of pure apocrine carcinomas than in the apocrine-like carcinomas group (76 vs 29%, P ¼ 0.006). In the pure apocrine carcinoma group, Her-2/ neu and EGFR protein expression were inversely correlated (P ¼ 0.006, r ¼ À0.499). EGFR gene amplification was observed in two pure apocrine carcinomas and one apocrine-like carcinoma. Polysomy 7 was commonly present in pure apocrine carcinomas (61 vs 27% of apocrine-like carcinomas; P ¼ 0.083) and showed a weak positive correlation with EGFR protein expression (P ¼ 0.025, r ¼ 0.326). Our study showed that apocrine breast carcinomas are molecularly diverse group of carcinomas. Strictly defined pure apocrine carcinomas are either HER-2-overexpressing breast carcinomas or triple-negative breast carcinomas, whereas apocrine-like carcinomas predominantly belong to the luminal phenotype. Pure apocrine carcinomas show consistent overexpression of either EGFR or HER-2/neu, which could have significant therapeutic implications.

Assessment of HER2 gene status in breast carcinomas with polysomy of chromosome 17

“…17 The present study also revealed a smaller overall proportion (12% of all tested cases) of increased CEP17 copy number cases, composed predominantly of invasive breast carcinomas of no special type. In addition, increased CEP17 copy number is frequently found in tumors showing HER2 overexpression, including those with a borderline (2þ) score, as confirmed in our study.…”

“…The primary mechanism of HER2 overexpression is amplification of the HER2 gene on chromosome 17,6 which is typically detected by fluorescence in situ hybridization (FISH), although other in situ hybridization methods are now increasingly used (chromogenic and silver in situ hybridization) as well as array comparative genomic hybridization. For FISH analysis, 3 kits approved by the US Food and Drug Administration are available: 1) PathVysion (Abbott Laboratories, Abbott Park, Ill), 2) INFORM (Ventana Medical Systems, Tucson, Ariz), or 3) PHarmDx (DAKO, Glostrup, Denmark).…”

Apocrine Carcinoma of Breast- A Rare Case Report

“…Reported incidences of HER-2 overexpression vary from 33% to 54%. 1,9,11 Gross cystic disease fluid protein 15 (GCDFP-15) has been identified as a marker for apocrine differentiation in breast; however, its expression appears to be decreased in advanced apocrine carcinomas. 12 Clinical and radiological presentation of apocrine carcinoma is no different from that of invasive ductal carcinomas (NST).…”

Immunohistochemical characterization of selected breast lesions

“…Apocrine carcinomas are defined as carcinomas in which the cells demonstrate the cytological features of apocrine cells [3], they are often ER-negative and PR-negative, but AR-positive tumors [16], and express apocrine markers like GCDFP-15. As concerns the molecular types approached by IHC, somewhat more than half of apocrine carcinomas represent a subgroup of TNBCs and nearly half of them overexpress HER2 [17]. A molecular apocrine type of breast cancer with increased androgen signaling has also been described, and is characterized by ER negativity and AR positivity [3,18,102,103].…”

“…ER and PR negativity, androgen receptor-(AR) positivity [16], with the co-expression of gross cystic disease fluid protein-15 (GCDFP-15) are considered as IHC criteria of apocrine differentiation. Somewhat more than half of apocrine carcinomas represent a subgroup of TNBCs and nearly half of them overexpress HER2 [17]. Recently a gene expression profile based category of molecular apocrine tumors has also been introduced [18].…”