Clinicopathological significance of TUBB3 in upper tract urothelial carcinoma and possible application in urine cytology.

IF 2.5 4区医学 Q2 PATHOLOGY Pathology International Pub Date : 2023-09-01 DOI:10.1111/pin.13362

Go Kobayashi, Tetsutaro Hayashi, Kazuhiro Sentani, Naohiro Uraoka, Takafumi Fukui, Aya Kido, Narutaka Katsuya, Akira Ishikawa, Takashi Babasaki, Yohei Sekino, Hiroyuki Nose, Nobuyuki Hinata, Naohide Oue

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Abstract

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.

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TUBB3在上尿路上皮癌中的临床病理意义及在尿细胞学上的应用前景。

β iii -微管蛋白是一种微管蛋白，由TUBB3基因编码。我们之前报道过TUBB3在肾细胞癌中过表达。应用免疫组织化学方法探讨TUBB3在上尿路上皮癌(UTUC)中的临床病理意义。在正常组织中，TUBB3表达弱或缺失。相比之下，103例尿路上皮癌(UC)中51例(49%)出现TUBB3过表达。TUBB3过表达与结节/扁平形态、高级别疾病、高T期和不良预后相关。在Cancer Genome Atlas膀胱癌队列中也得到了类似的结果。TUBB3的表达还与UTUC中Ki-67标记指数、CD44v9、HER2、EGFR和p53的高表达相关。在具有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，我们利用尿液细胞学样本，通过免疫细胞化学分析TUBB3的表达。TUBB3在UC细胞中的表达比在非肿瘤细胞中更常见。联合TUBB3免疫染色可提高尿细胞学诊断的准确性。这些发现提示TUBB3在肿瘤进展中的重要性及其作为UC高级别疾病和预后的生物标志物的潜在应用。此外，联合TUBB3免疫染色可提高尿细胞学诊断的准确性。

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来源期刊

Pathology International 医学-病理学

CiteScore

4.50

自引率

4.50%

发文量

102

审稿时长

12 months

期刊介绍： Pathology International is the official English journal of the Japanese Society of Pathology, publishing articles of excellence in human and experimental pathology. The Journal focuses on the morphological study of the disease process and/or mechanisms. For human pathology, morphological investigation receives priority but manuscripts describing the result of any ancillary methods (cellular, chemical, immunological and molecular biological) that complement the morphology are accepted. Manuscript on experimental pathology that approach pathologenesis or mechanisms of disease processes are expected to report on the data obtained from models using cellular, biochemical, molecular biological, animal, immunological or other methods in conjunction with morphology. Manuscripts that report data on laboratory medicine (clinical pathology) without significant morphological contribution are not accepted.