背景:我们先前报道了微小染色体维持4(MCM4)在胃癌中的过表达。然而,MCM4在尿路上皮癌(UC)中的临床病理意义尚未研究。阐明MCM4在UC中的临床病理意义。我们用免疫组织化学(IHC)研究了MCM4的表达。
方法:我们通过IHC分析了124例上尿路尿路上皮癌(UTUC)样本中MCM4的表达和分布。此外,使用108个尿液样本,我们分析了MCM4免疫细胞化学(ICC)在尿细胞学中的表达。
结果:在正常尿路上皮中,MCM4表达较弱或缺失。同时,在UTUC组织中观察到MCM4的强核表达,在124例UTUC病例中的77例(62%)中检测到。MCM4阳性UTUC病例与结节状/扁平形态相关,高品位,高T阶段,预后不良。此外,MCM4在侵袭性前缘的表达明显高于肿瘤表面。在TCGA膀胱癌队列中也获得了类似的结果。此外,MCM4表达与Ki-67、HER2、EGFR、和UTUC中的p53。在代表性的癌症相关分子中,MCM4对无进展生存期和高级别UC具有独立的预测价值。MCM4的ICC也在尿细胞学载玻片上进行,并显示MCM4的核表达在UC细胞中比非肿瘤细胞中更常见。通过将MCM4免疫染色与细胞学相结合,提高了尿细胞学的诊断准确性。
结论:这些结果表明MCM4可能是高级组织学的有用预测生物标志物,UC的肿瘤进展和不良预后。此外,MCM4的ICC可能有助于UC检测,作为基于细胞形态学的诊断中的其他标志物。
BACKGROUND: We previously reported Minichromosome maintenance 4 (MCM4) overexpression in gastric cancer. However, the clinicopathological significance of MCM4 in urothelial carcinoma (UC) has not been investigated. To clarify the clinicopathological significance of MCM4 in UC, we investigated MCM4 expression with immunohistochemistry (IHC).
METHODS: We analyzed the expression and distribution of MCM4 in 124 upper tract urothelial carcinoma (UTUC) samples by IHC. Additionally, using 108 urine samples, we analyzed MCM4 Immunocytochemistry (ICC) expression in urine cytology.
RESULTS: In normal urothelium, MCM4 expression was weak or absent. Meanwhile, the strong nuclear expression of MCM4 was observed in UTUC tissues, and it was detected in 77 (62%) of a total of 124 UTUC cases. MCM4-positive UTUC cases were associated with nodular/flat morphology, high grade, high T stage, and poor prognosis. Moreover, MCM4 expression was significantly higher in the invasive front than in the tumor surface. Similar results were also obtained in TCGA bladder cancer cohort. Additionally, MCM4 expression was associated with high expression of Ki-67, HER2, EGFR, and p53 in UTUC. Among representative cancer-related molecules, MCM4 had an independent predictive value for progression-free survival and high-grade UC. ICC for MCM4 was also performed on urine cytology slides and showed that the nuclear expression of MCM4 was more frequently found in UC cells than in non-neoplastic cells. The diagnostic accuracy of urine cytology was improved by combining MCM4 immunostaining with cytology.
CONCLUSIONS: These results suggest that MCM4 might be a useful predictive biomarker for high-grade histology, tumor progression and poor prognosis in UC. Moreover, ICC for MCM4 might be helpful for UC detection as additional markers in the cytomorphology-based diagnosis.