Department of Pathology, University of California San Francisco (UCSF), San Francisco, California.
Department of Pathology, Stanford University School of Medicine, Stanford, California.
Mod Pathol. 2023 May;36(5):100125. doi: 10.1016/j.modpat.2023.100125. Epub 2023 Feb 6.
Triple-negative apocrine carcinomas (TNACs) are rare breast tumors with limited studies evaluating their molecular characteristics and clinical behavior. We performed a histologic, immunohistochemical, genetic, and clinicopathologic assessment of 42 invasive TNACs (1 with a focal spindle cell component) from 41 patients, 2 pure apocrine ductal carcinomas in situ (A-DCIS), and 1 A-DCIS associated with spindle cell metaplastic carcinoma (SCMBC). All TNACs had characteristic apocrine morphology and expressed androgen receptor (42/42), gross cystic disease fluid protein 15 (24/24), and CK5/6 (16/16). GATA3 was positive in most cases (16/18, 89%), and SOX10 was negative (0/22). TRPS1 was weakly expressed in a minority of tumors (3/14, 21%). Most TNACs had low Ki67 proliferation (≤10% in 67%, 26/39), with a median index of 10%. Levels of tumor infiltrating lymphocytes were low (≤10% in 93%, 39/42, and 15% in 7%, 3/42). Eighteen percent of TNACs presented with axillary nodal metastasis (7/38). No patients treated with neoadjuvant chemotherapy achieved pathologic complete response (0%, 0/10). Nearly all patients with TNAC (97%, n = 32) were without evidence of disease at the time of study (mean follow-up of 62 months). Seventeen invasive TNACs and 10 A-DCIS (7 with paired invasive TNAC) were profiled by targeted capture-based next-generation DNA sequencing. Pathogenic mutations in phosphatidylinositol 3-kinase pathway genes PIK3CA (53%) and/or PIK3R1 (53%) were identified in all TNACs (100%), including 4 (24%) with comutated PTEN. Ras-MAPK pathway genes, including NF1 (24%), and TP53 were mutated in 6 tumors each (35%). All A-DCIS shared mutations, such as phosphatidylinositol 3-kinase aberrations and copy number alterations with paired invasive TNACs or SCMBC, and a subset of invasive carcinomas showed additional mutations in tumor suppressors (NF1, TP53, ARID2, and CDKN2A). Divergent genetic profiles between A-DCIS and invasive carcinoma were identified in 1 case. In summary, our findings support TNAC as a morphologically, immunohistochemically, and genetically homogeneous subgroup of triple-negative breast carcinomas and suggest overall favorable clinical behavior.
三阴性大汗腺癌（TNACs）是一种罕见的乳腺肿瘤，目前对其分子特征和临床行为的研究有限。我们对 41 例患者的 42 例浸润性 TNAC（1 例伴局灶性梭形细胞成分）、2 例单纯大汗腺导管原位癌（A-DCIS）和 1 例与梭形细胞化生癌（SCMBC）相关的 A-DCIS 进行了组织学、免疫组织化学、遗传学和临床病理评估。所有 TNAC 均具有特征性大汗腺形态，并表达雄激素受体（42/42）、大体囊性疾病液体蛋白 15（24/24）和 CK5/6（16/16）。GATA3 在大多数病例中呈阳性（16/18，89%），而 SOX10 呈阴性（0/22）。TRPS1 在少数肿瘤中呈弱阳性表达（3/14，21%）。大多数 TNAC 的 Ki67 增殖较低（≤10%，67%，26/39），中位数为 10%。肿瘤浸润淋巴细胞水平较低（≤10%，93%，39/42；15%，7%，3/42）。18%的 TNAC 出现腋窝淋巴结转移（7/38）。接受新辅助化疗的患者无一例达到病理完全缓解（0%，0/10）。几乎所有 TNAC 患者（97%，n=32）在研究时均无疾病证据（中位随访 62 个月）。17 例浸润性 TNAC 和 10 例 A-DCIS（7 例与配对浸润性 TNAC 相关）采用基于靶向捕获的下一代 DNA 测序进行了分析。所有 TNAC 均存在磷脂酰肌醇 3-激酶途径基因 PIK3CA（53%）和/或 PIK3R1（53%）的致病性突变（100%），包括 4 例（24%）存在共突变的 PTEN。Ras-MAPK 途径基因，包括 NF1（24%）和 TP53，在 6 个肿瘤中各有 6 个（35%）发生突变。所有 A-DCIS 与配对的浸润性 TNAC 或 SCMBC 具有相同的突变，如磷脂酰肌醇 3-激酶异常和拷贝数改变，一部分浸润性癌还存在肿瘤抑制基因（NF1、TP53、ARID2 和 CDKN2A）的额外突变。在 1 例中发现 A-DCIS 和浸润性癌之间存在不同的遗传特征。总之，我们的研究结果支持将 TNAC 作为一种形态学、免疫组织化学和遗传学上均具有同质性的三阴性乳腺癌亚群，并提示总体预后良好。
