Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Mod Pathol. 2021 Apr;34(4):710-719. doi: 10.1038/s41379-020-00692-8. Epub 2020 Oct 3.
Currently there is no highly specific and sensitive marker to identify breast cancer-the most common malignancy in women. Breast cancer can be categorized as estrogen receptor (ER)/progesterone receptor (PR)-positive luminal, human epidermal growth factor receptor 2 (HER2)-positive, or triple-negative breast cancer (TNBC) types based on the expression of ER, PR, and HER2. Although GATA3 is the most widely used tumor marker at present to determine the breast origin, which has been shown to be an excellent marker for ER-positive and low-grade breast cancer, but it does not work well for TNBC with sensitivity as low as <20% in metaplastic breast carcinoma. In the current study, through TCGA data mining we identified trichorhinophalangeal syndrome type 1 (TRPS1) as a specific gene for breast carcinoma across 31 solid tumor types. Moreover, high mRNA level of TRPS1 was found in all four subtypes of breast carcinoma including ER/PR-positive luminal A and B types, HER2-positive type, and basal-type/TNBC. We then analyzed TRPS1 expression in 479 cases of various types of breast cancer using immunochemistry staining, and found that TRPS1 and GATA3 had comparable positive expression in ER-positive (98% vs. 95%) and HER2-positive (87% vs. 88%) breast carcinomas. However, TRPS1 which was highly expressed in TNBC, was significantly higher than GATA3 expression in metaplastic (86% vs. 21%) and nonmetaplastic (86% vs. 51%) TNBC. In addition, TRPS1 expression was evaluated in 1234 cases of solid tumor from different organs. In contrast to the high expression of GATA3 in urothelial carcinoma, TRPS1 showed no or little expression in urothelial carcinomas or in other tumor types including lung adenocarcinoma, pancreatic adenocarcinoma, colon and gastric adenocarcinoma, renal cell carcinoma, melanoma, and ovarian carcinoma. These findings suggest that TRPS1 is a highly sensitive and specific marker for breast carcinoma and can be used as a great diagnostic tool, especially for TNBC.
目前，尚无高度特异性和敏感性标志物可用于识别乳腺癌——女性中最常见的恶性肿瘤。乳腺癌可根据 ER、PR 和 HER2 的表达情况分为雌激素受体（ER）/孕激素受体（PR）阳性 luminal 型、人表皮生长因子受体 2（HER2）阳性型或三阴性乳腺癌（TNBC）型。尽管 GATA3 目前是最广泛用于确定乳腺癌来源的肿瘤标志物，已被证明是 ER 阳性和低级别乳腺癌的优秀标志物，但在具有低至<20%敏感性的癌肉瘤样乳腺癌中效果不佳。在本研究中，通过 TCGA 数据挖掘，我们发现 Trichorhinophalangeal Syndrome Type 1（TRPS1）是 31 种实体瘤类型中乳腺癌的特异性基因。此外，在包括 ER/PR 阳性 luminal A 和 B 型、HER2 阳性型和基底型/TNBC 在内的所有四种乳腺癌亚型中，均发现 TRPS1 的 mRNA 水平较高。然后，我们使用免疫组织化学染色分析了 479 例各种类型乳腺癌中的 TRPS1 表达，发现 TRPS1 和 GATA3 在 ER 阳性（98%对 95%）和 HER2 阳性（87%对 88%）乳腺癌中具有可比的阳性表达。然而，在 TNBC 中高表达的 TRPS1，在癌肉瘤样（86%对 21%）和非癌肉瘤样（86%对 51%）TNBC 中，明显高于 GATA3 的表达。此外，还评估了来自不同器官的 1234 例实体瘤中的 TRPS1 表达。与尿路上皮癌中 GATA3 的高表达形成对比的是，TRPS1 在尿路上皮癌或其他肿瘤类型（包括肺腺癌、胰腺腺癌、结肠和胃腺癌、肾细胞癌、黑色素瘤和卵巢癌）中无表达或表达很少。这些发现表明，TRPS1 是一种高度敏感和特异的乳腺癌标志物，可作为一种很好的诊断工具，特别是用于 TNBC。
