Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Canada.
Int J Surg Pathol. 2024 Apr;32(2):239-251. doi: 10.1177/10668969231171936. Epub 2023 Jun 12.
Triple negative breast carcinomas are characterized by a lack of hormone receptor and HER2 expression and inconsistent expression of breast-specific immunohistochemical markers. The expression of many site-specific markers in these tumors is largely unknown. The objective of the study was to examine the expression of widely used immunohistochemical markers on a large cohort of triple negative breast cancer. Sections from tissue microarrays were stained with 47 markers using routine protocols. Most markers were scored using a modified Allred method. ATRX, BAP1, SMAD4, e-cadherin, and beta-catenin were scored as retained or lost. Mammaglobin was considered positive if there was at least moderate intensity staining in any tumor cells. P16 was scored as overexpressed or not overexpressed; p53 was scored as wildtype, overexpressed, null, or cytoplasmic. The cohort consisted of 639 tumors including 601 primary and 32 metastases. Overall, 96% expressed GATA3, mammaglobin, and/or SOX10 while 97% of no special type tumors expressed this panel. Carcinoma of apocrine differentiation demonstrated an AR positive, SOX10 negative, K5 negative/focal immunophenotype. PAX8 (SP348), WT1, Napsin A, and TTF1 (8G7G3/1) were never or rarely expressed while CA9, CDX2, NKX3.1, SATB2 (SATBA410), synaptophysin, and vimentin were variably expressed. Almost all TNBC express at least 1 of the 3 IHC markers: GATA3, mammaglobin, and/or SOX10. Carcinoma of apocrine differentiation is characterized by an AR positive, SOX10 negative, K5 negative or focal immunophenotype. Cautious interpretation of so-called site-specific markers, with knowledge of antibody clones, is required in excluding the diagnosis of triple negative breast cancer.
三阴性乳腺癌的特征是缺乏激素受体和 HER2 表达，以及乳腺特异性免疫组化标志物的不一致表达。这些肿瘤中许多特定部位标志物的表达情况在很大程度上尚不清楚。本研究的目的是在一个大的三阴性乳腺癌队列中检查广泛使用的免疫组化标志物的表达情况。使用常规方案对组织微阵列的切片进行 47 种标志物的染色。大多数标志物使用改良的 Allred 评分法进行评分。ATRX、BAP1、SMAD4、E-钙黏蛋白和β-连环蛋白的评分结果为保留或丢失。如果肿瘤细胞中有至少中度强度的染色，则认为 mammaglobin 阳性。P16 的评分结果为过表达或不过表达；p53 的评分结果为野生型、过表达、缺失或细胞质。该队列包括 639 例肿瘤，其中包括 601 例原发性肿瘤和 32 例转移瘤。总体而言，96%的肿瘤表达 GATA3、mammaglobin 和/或 SOX10，而 97%的非特殊类型肿瘤表达这一组标志物。大汗腺癌表现为 AR 阳性、SOX10 阴性、K5 阴性/局灶性免疫表型。PAX8（SP348）、WT1、Napsin A 和 TTF1（8G7G3/1）从未或很少表达，而 CA9、CDX2、NKX3.1、SATB2（SATBA410）、突触素和波形蛋白则呈不同程度的表达。几乎所有的三阴性乳腺癌都至少表达 1 种免疫组化标志物：GATA3、mammaglobin 和/或 SOX10。大汗腺癌的特征是 AR 阳性、SOX10 阴性、K5 阴性或局灶性免疫表型。在排除三阴性乳腺癌的诊断时，需要谨慎解释所谓的特定部位标志物，并了解抗体克隆。
