Laboratory of Molecular Pathology, Department of Molecular Biosciences, Radiation Effects Research Foundation, Hiroshima, Japan.
Department of Pathology, Kure-Kyosai Hospital, Federation of National Public Service Personnel Mutual Aid Associations, Hiroshima, Japan.
Pathol Int. 2023 Sep;73(9):444-455. doi: 10.1111/pin.13362. Epub 2023 Aug 17.
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.
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方法研究了 TUBB3 在尿路上皮癌（UTUC）中的临床病理意义。在正常组织中，TUBB3 表达较弱或缺失。相比之下，在 103 例 UTUC 病例中的 51 例（49%）尿路上皮癌组织中观察到 TUBB3 过表达。TUBB3 过表达与结节/扁平形态、高级别疾病、高 T 分期和预后不良有关。在 The Cancer Genome Atlas 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 表达有关。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，我们使用尿细胞学样本通过免疫细胞化学分析 TUBB3 表达。在 UC 细胞中比在非肿瘤细胞中更频繁地发现 TUBB3 表达。当与 TUBB3 免疫染色结合使用时，尿细胞学的诊断准确性得到提高。这些发现表明 TUBB3 在肿瘤进展中的重要性及其作为高级别疾病和 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的诊断准确性。
