Apocrine-Eccrine Carcinomas: Molecular and Immunohistochemical Analyses

Abstract

Apocrine-eccrine carcinomas are rare and associated with poor prognosis. Currently there is no uniform treatment guideline. Chemotherapeutic drugs that selectively target cancer-promoting pathways may complement conventional therapeutic approaches. However, studies on genetic alterations and EGFR and Her2 status of apocrine-eccrine carcinomas are few in number. In addition, hormonal studies have not been comprehensive and performed only on certain subsets of apocrine-eccrine carcinomas. To investigate whether apocrine-eccrine carcinomas express hormonal receptors or possess activation of oncogenic pathways that can be targeted by available chemotherapeutic agent we performed immunohistochemistry for AR, PR, ER, EGFR, and HER2 expression; fluorescence in situ hybridization (FISH) for EGFR and ERBB2 gene amplification; and molecular analyses for recurrent mutations in 15 cancer genes including AKT-1, EGFR, PIK3CA, and TP53 on 54 cases of apocrine-eccrine carcinomas. They include 10 apocrine carcinomas, 7 eccrine carcinomas, 9 aggressive digital papillary adenocarcinomas, 10 hidradenocarcinomas, 11 porocarcinomas, 1 adenoid cystic carcinoma, 4 malignant chondroid syringomas, 1 malignant spiradenoma, and 1 malignant cylindroma. AR, ER, PR, EGFR and HER2 expression was seen in 36% (19/53), 27% (14/51), 16% (8/51), 85% (44/52) and 12% (6/52), respectively. Polysomy or trisomy of EGFR was detected by FISH in 30% (14/46). Mutations of AKT-1, PIK3CA, and TP53 were detected in 1, 3, and 7 cases, respectively (11/47, 23%). Additional investigation regarding the potential treatment of rare cases of apocrine-eccrine carcinomas with PI3K/Akt/mTOR pathway inhibitors, currently in clinical testing, may be of clinical interest.

Altered Rb, p16, and p53 expression is specific for porocarcinoma relative to poroma

“…Thus far, there is limited data regarding genetic changes associated with malignant progression in these tumors. Activating mutations in HRAS , PIK3CA , and possibly EGFR may serve as oncogenic drivers . Of these, HRAS mutations have also been reported in poromas .…”

Vulvar Adnexal Lesions: A 32-Year, Single-Institution Review From Massachusetts General Hospital

“…110 The TP53 mutation has been reported in 2 cases of spiradenocarcinomas 81 and one case of malignant cylindroma. 79 Chondroid Syringoma and Malignant Chondroid Syringoma.-Chondroid syringoma, also known as benign mixed tumor, is a rare tumor of the vulva, with only a few cases reported in the literature. [111][112][113][114][115] In the vulva, these lesions are thought to arise from underlying sweat glands or Bartholin glands.…”

“…Studies have shown a strong correlation of androgen receptor expression in cutaneous apocrine carcinoma, raising the potential for antiandrogen therapy. 79,118 Extramammary Paget Disease.-Extramammary Paget disease can be either primary or secondary. Primary EMPD can be either an intraepithelial neoplasm with or without an associated invasive component or a manifestation of an underlying primary adenocarcinoma.…”

“…74,78,79 Although atypical and malignant hidradenomas express EGFR, only occasional cases with gene polysomy and no gene amplification were found. 79,80 In rare cases of hidradenocarcinomas mutations of TP53, 74,79,81 PIK3CA, 79 and AKT-1 79 have been documented. Poroma and Porocarcinoma.-Although eccrine poroma, a tumor derived from the acrosyringium, most often presents on plantar or palmar skin, it may occur at any site containing sweat glands.…”

“…87 Regarding molecular studies, TP53 and PIK3CA mutations and EGFR gene polysomy have been documented in rare cases of porocarcinomas. 78,79,81 Eccrine Carcinoma.-The overlapping features of eccrine carcinoma and adenocarcinoma of mammary-like glands make this distinction challenging. 4,88 Furthermore, both entities can express estrogen receptor, progesterone receptor, or gross cystic disease fluid protein-15.…”