Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY 10065, USA.
Hum Pathol. 2013 Oct;44(10):2282-92. doi: 10.1016/j.humpath.2013.05.010. Epub 2013 Jul 12.
Trefoil factor 3 (TFF3) is associated with various cancers and overexpressed in a subset of prostate cancers. Functional studies suggest that v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) down-regulates TFF3 expression in hormone-naïve prostate cancer. To characterize this inverse relationship, we developed a triple immunostain encompassing ERG, TFF3, and high-molecular-weight cytokeratin. Triple stain was performed on 96 tumors and 52 benign cases represented in tissue microarrays. Distinct ERG and TFF3 protein was expressed in 45% (43/96) and 36% (35/96) of prostate cancers, respectively. Coexpression was observed in 5% (5/96) of tumor cases, and 24% (23/96) did not express ERG or TFF3. The inverse expression of ERG and TFF3 was significant (P < .0001), with 57% (30/53) of ERG-negative tumors demonstrating TFF3 expression. Sensitivity and specificity of combined ERG and TFF3 expression in detecting prostate cancer were 76% and 96%, respectively. The feasibility of triple immunostain protocol was validated in a set of 76 needle biopsies. The application of this multiplex in situ biomarker for molecular characterization of prostate cancer and as a supplemental diagnostic and prognostic tool in prostate needle biopsies should be further explored.
三叶因子 3（TFF3）与多种癌症相关，在一部分前列腺癌中过度表达。功能研究表明，v-ets 红细胞生成病毒 E26 癌基因同源物（禽）（ERG）下调激素-naive 前列腺癌中的 TFF3 表达。为了描述这种反向关系，我们开发了一种包含 ERG、TFF3 和高分子量细胞角蛋白的三重免疫染色。三重染色在组织微阵列中 96 个肿瘤和 52 个良性病例中进行。分别在 45%（43/96）和 36%（35/96）的前列腺癌中观察到明显的 ERG 和 TFF3 蛋白表达。在 5%（5/96）的肿瘤病例中观察到共表达，而 24%（23/96）的病例既不表达 ERG 也不表达 TFF3。ERG 和 TFF3 的反向表达具有统计学意义（P<0.0001），57%（30/53）的 ERG 阴性肿瘤表现出 TFF3 表达。联合 ERG 和 TFF3 表达检测前列腺癌的敏感性和特异性分别为 76%和 96%。该三重免疫染色方案在 76 例针吸活检中的可行性已得到验证。这种多指标原位生物标志物在前列腺癌的分子特征分析中的应用以及作为前列腺针吸活检的辅助诊断和预后工具应进一步探索。
