βIII-Tubulin, encoded by the TUBB3 gene, is a microtubule protein. We previously reported that TUBB3 is overexpressed in renal cell carcinoma. We investigated the clinicopathological significance of TUBB3 in upper tract urothelial carcinoma (UTUC) by immunohistochemistry. In normal tissue, TUBB3 expression was weak or absent. In contrast, TUBB3 overexpression was observed in urothelial carcinoma (UC) tissues in 51 (49%) of 103 UTUC cases. TUBB3 overexpression was associated with nodular/flat morphology, high-grade disease, high T stage, and a poor prognosis. Similar results were obtained in The Cancer Genome Atlas bladder cancer cohort. TUBB3 expression was also associated with high Ki-67 labeling index, CD44v9, HER2, EGFR, and p53 expression in UTUC. Among representative cancer-related molecules, TUBB3 was an independent predictor of progression-free survival and high-grade UC. Finally, using urine cytology samples, we analyzed TUBB3 expression by immunocytochemistry. TUBB3 expression was more frequently found in UC cells than in nonneoplastic cells. The diagnostic accuracy of urine cytology was improved when combined with TUBB3 immunostaining. The findings suggest the importance of TUBB3 in tumor progression and its potential application as a biomarker for high-grade disease and the prognosis of UC. Moreover, combination with TUBB3 immunostaining might improve the diagnostic accuracy of urine cytology.

中文翻译：

---

TUBB3在上尿路尿路上皮癌中的临床病理意义及其在尿液细胞学中的可能应用

βIII-微管蛋白由 TUBB3 基因编码，是一种微管蛋白。我们之前报道过 TUBB3 在肾细胞癌中过度表达。我们通过免疫组织化学研究了 TUBB3 在上尿路尿路上皮癌 (UTUC) 中的临床病理学意义。在正常组织中，TUBB3表达较弱或不表达。相比之下，在 103 例 UTUC 病例中，有 51 例 (49%) 在尿路上皮癌 (UC) 组织中观察到 TUBB3 过度表达。TUBB3 过表达与结节/扁平形态、高级别疾病、高 T 分期和不良预后相关。在癌症基因组图谱膀胱癌队列中也获得了类似的结果。TUBB3 表达还与 UTUC 中的高 Ki-67 标记指数、CD44v9、HER2、EGFR 和 p53 表达相关。在代表性的癌症相关分子中，TUBB3是无进展生存期和高级别UC的独立预测因子。最后，使用尿液细胞学样本，我们通过免疫细胞化学分析了 TUBB3 的表达。TUBB3 表达在 UC 细胞中比在非肿瘤细胞中更常见。与TUBB3免疫染色联合使用可提高尿细胞学诊断的准确性。这些发现表明 TUBB3 在肿瘤进展中的重要性及其作为高级疾病和 UC 预后的生物标志物的潜在应用。此外，与TUBB3免疫染色相结合可能会提高尿细胞学诊断的准确性。