Apocrine-Eccrine Carcinomas: Molecular and Immunohistochemical Analyses

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.

顶泌汗腺-小汗腺癌（Apocrine-eccrine carcinomas）是一类罕见肿瘤，且预后不良，目前尚无统一的治疗指南。能够选择性靶向促癌通路的化疗药物或可补充传统治疗方案，但目前针对顶泌汗腺-小汗腺癌的基因改变、表皮生长因子受体（EGFR）及人表皮生长因子受体2（HER2）状态的研究数量较少。此外，相关激素研究尚未形成体系，且仅针对顶泌汗腺-小汗腺癌的特定亚组开展。
为明确顶泌汗腺-小汗腺癌是否表达激素受体，或是否存在可通过现有化疗药物靶向的致癌通路激活，本研究对54例顶泌汗腺-小汗腺癌标本开展了如下检测：针对雄激素受体（AR）、孕激素受体（PR）、雌激素受体（ER）、EGFR及HER2表达的免疫组化检测；针对EGFR及ERBB2基因扩增的荧光原位杂交（FISH）检测；以及针对AKT-1、EGFR、PIK3CA、TP53等15个癌症相关基因频发突变的分子分析。
本次研究纳入的54例标本涵盖以下亚型：10例顶泌汗腺癌、7例小汗腺癌、9例侵袭性数字乳头状腺腺癌、10例汗腺癌、11例汗孔癌（porocarcinoma）、1例腺样囊性癌、4例恶性软骨样汗管瘤、1例恶性螺旋腺瘤及1例恶性圆柱瘤。
AR、ER、PR、EGFR及HER2的阳性表达率分别为36%（19/53）、27%（14/51）、16%（8/51）、85%（44/52）及12%（6/52）。
通过FISH检测，30%（14/46）的标本可检出EGFR多体性或三体性。
AKT-1、PIK3CA及TP53的突变检出率分别为1例、3例及7例，共计11例，占可评估病例的23%（11/47）。
针对使用目前处于临床试验阶段的PI3K/Akt/mTOR通路抑制剂治疗罕见顶泌汗腺-小汗腺癌的潜在方案开展进一步研究，或具有重要临床价值。