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.
Highlights
In a recent World Health Organization (WHO) classification of cutaneous appendageal carcinomas; apocrine-eccrine, follicular, and sebaceous carcinomas were the three main categories cited in the consensus classification after taking into account the clinical, histologic, and molecular genetic features [1]
Widespread metastases developed in one patient with eccrine carcinoma that resulted in death (Table 2)
It is known that apocrine-eccrine carcinomas often express estrogen receptor and progesterone receptor [21,23]
Summary
In a recent World Health Organization (WHO) classification of cutaneous appendageal carcinomas; apocrine-eccrine, follicular, and sebaceous carcinomas were the three main categories cited in the consensus classification after taking into account the clinical, histologic, and molecular genetic features [1]. Apocrine-eccrine carcinomas are rare and associated with poor prognosis [2,3,4]. Three of nine cases of clear cell eccrine carcinomas reported by Wong et al [4] developed metastases despite local excision, radiation, and chemotherapy. In recent Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute data from 1978 through 2005, the incidence rate of apocrine-eccrine carcinomas was reported to be 2.6 per 1 million person-years [2]. The five-year relative survival rates for apocrine-eccrine carcinomas were 99% for localized, 94% for regional and 51% for distant disease [2]
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