Higgins John P T, Kaygusuz Gulsah, Wang Lingli, Montgomery Kelli, Mason Veronica, Zhu Shirley X, Marinelli Robert J, Presti Joseph C, van de Rijn Matt, Brooks James D
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Am J Surg Pathol. 2007 May;31(5):673-80. doi: 10.1097/01.pas.0000213438.01278.5f.
The morphologic distinction between prostate and urothelial carcinoma can be difficult. To identify novel diagnostic markers that may aid in the differential diagnosis of prostate versus urothelial carcinoma, we analyzed expression patterns in prostate and bladder cancer tissues using complementary DNA microarrays. Together with our prior studies on renal neoplasms and normal kidney, these studies suggested that the gene for placental S100 (S100P) is specifically expressed in benign and malignant urothelial cells. Using tissue microarrays, a polyclonal antiserum against S100P protein stained 86% of 295 urothelial carcinomas while only 3% of 260 prostatic adenocarcinomas and 1% of 133 renal cell carcinomas stained. A commercially available monoclonal antibody against S100P stained 78% of 300 urothelial carcinomas while only 2% of 256 prostatic adenocarcinomas and none of 137 renal cell carcinomas stained. A second gene, GATA3, also showed high level expression in urothelial tumors by cDNA array. A commercially available monoclonal antibody against GATA3 stained 67% of 308 urothelial carcinomas, but none of the prostate or renal carcinomas. For comparison, staining was also performed for p63 and cytokeratin 5/6. p63 stained 87% of urothelial carcinomas whereas CK5/6 stained 54%. Importantly, when S100P and p63 were combined 95% of urothelial carcinomas were labeled by one or both markers. We conclude that the detection of S100P and GATA3 protein expression may help distinguish urothelial carcinomas from other genitourinary neoplasms that enter into the differential diagnosis.
前列腺癌和尿路上皮癌之间的形态学区分可能存在困难。为了确定有助于前列腺癌与尿路上皮癌鉴别诊断的新型诊断标志物,我们使用互补DNA微阵列分析了前列腺癌和膀胱癌组织中的表达模式。结合我们之前对肾肿瘤和正常肾脏的研究,这些研究表明胎盘S100(S100P)基因在良性和恶性尿路上皮细胞中特异性表达。使用组织微阵列,一种针对S100P蛋白的多克隆抗血清对295例尿路上皮癌中的86%进行了染色,而260例前列腺腺癌中只有3%、133例肾细胞癌中只有1%被染色。一种市售的针对S100P的单克隆抗体对300例尿路上皮癌中的78%进行了染色,而256例前列腺腺癌中只有2%被染色,137例肾细胞癌均未被染色。另一个基因GATA3在cDNA阵列分析中也显示在尿路上皮肿瘤中高表达。一种市售的针对GATA3的单克隆抗体对308例尿路上皮癌中的67%进行了染色,但前列腺癌和肾癌均未被染色。作为对照,还对p63和细胞角蛋白5/6进行了染色。p63对87%的尿路上皮癌进行了染色,而CK5/6对54%的尿路上皮癌进行了染色。重要的是,当S100P和p63联合使用时,95%的尿路上皮癌被一种或两种标志物标记。我们得出结论,检测S100P和GATA3蛋白表达可能有助于将尿路上皮癌与其他需要进行鉴别诊断的泌尿生殖系统肿瘤区分开来。