Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Histopathology. 2022 Feb;80(3):589-597. doi: 10.1111/his.14592. Epub 2021 Dec 16.
Basal-like breast cancer is an aggressive molecular subtype associated with younger age and early relapse. Most cases lack expression of oestrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2, limiting targeted therapeutic options. Basal-like breast cancer is defined by the expression of genes in the outer/basally located epithelial layer of mammary glands, including those encoding cytokeratin (CK) 5 and CK14, and epidermal growth factor receptor (EGFR). SRY-box transcription factor 10 (SOX10), for which there is a readily available immunohistochemical stain, is expressed in a subset of breast cancers, particularly triple-negative carcinomas. In this study, we sought to: (i) assess the association between SOX10 expression and intrinsic molecular subtypes as defined by Prediction Analysis of Microarray 50 (PAM50) gene expression; and (ii) compare the performance of SOX10 with that of other surrogate markers of the basal-like subtype, including CK5, EGFR, nestin, and inositol polyphosphate 4-phosphatase type II (INPP4B).
SOX10 immunostaining was performed on tissue microarrays constructed from a contemporary series enriched for ER-negative and weakly ER-positive cancers that had also undergone PAM50 gene profiling. A total of 211 cases were informative for both SOX10 immunohistochemistry and PAM50 subtype, including 103 basal-like cancers. Staining for SOX10 was positive in 73 of 103 basal-like cancers and in only two of 108 cancers of other subtypes (P < 0.001), resulting in a sensitivity of 70.9% and a specificity of 98.1%. SOX10 was more specific than the other tested basal markers, and the results were independent of ER status.
SOX10 is a moderately sensitive, but highly specific, immunohistochemical biomarker for the basal-like intrinsic subtype of breast cancer, which, unlike other commonly used immunohistochemical biomarkers, is independent of hormone receptor status.
基底样乳腺癌是一种侵袭性的分子亚型，与年龄较小和早期复发有关。大多数病例缺乏雌激素受体（ER）、孕激素受体和人表皮生长因子受体 2 的表达，限制了靶向治疗选择。基底样乳腺癌是由乳腺外/基底上皮层表达的基因定义的，包括编码细胞角蛋白（CK）5 和 CK14 的基因，以及表皮生长因子受体（EGFR）。性别决定区 Y 框转录因子 10（SOX10）在一组乳腺癌中表达，特别是三阴性癌，对于 SOX10 有现成的免疫组织化学染色。在这项研究中，我们试图：（i）评估 SOX10 表达与通过微阵列 50（PAM50）基因表达预测分析定义的固有分子亚型之间的关联；（ii）比较 SOX10 与其他基底样亚型替代标志物的性能，包括 CK5、EGFR、巢蛋白和肌醇多磷酸 4-磷酸酶 II（INPP4B）。
对从富含 ER 阴性和弱 ER 阳性癌症的当代系列中构建的组织微阵列进行 SOX10 免疫组织化学染色，这些癌症也进行了 PAM50 基因分析。共有 211 例病例的 SOX10 免疫组织化学和 PAM50 亚型均有信息，包括 103 例基底样癌。在 103 例基底样癌中有 73 例染色阳性，而在 108 例其他亚型癌中只有 2 例阳性（P<0.001），敏感性为 70.9%，特异性为 98.1%。SOX10 的特异性高于其他测试的基底标志物，并且结果独立于 ER 状态。
SOX10 是一种中度敏感但高度特异的基底样乳腺癌内在亚型的免疫组织化学标志物，与其他常用的免疫组织化学标志物不同，它独立于激素受体状态。
