膀胱移行细胞癌中PAK1蛋白表达及其临床意义

目的探讨p21-激活激酶1（PAK1）基因在膀胱移行细胞癌中的蛋白表达及其临床病理学意义。方法运用免疫组化和TUNEL方法,结合组织芯片技术,检测PAK1基因在100例膀胱移型细胞癌和30例癌旁正常膀胱黏膜组织中的表达及其与细胞凋亡的关系。结果全部正常膀胱黏膜组织均呈PAK1蛋白阴性或低水平的表达。膀胱移行细胞癌中,有58％出现PAK1蛋白的过度表达;而且与肿瘤的病理分级和瘤体大小均有显著的相关性（P〈0．05）,其中78％分化差（G3级）和73％瘤体直径≥3cm的膀胱癌出现PAK1蛋白过度表达,其过度表达率明显高于分化较好（G1／G2级）（47％）和瘤体直径〈3cm（50％）的肿瘤。另外,PAK1蛋白表达与本组膀胱移行细胞癌的细胞凋亡指数负相关（P〈0．05）。结论膀胱移行细胞癌中PAK1蛋白表达上调可能部分地通过其抗细胞凋亡效应,在肿瘤的发生发展中起重要作用;PAK1过度表达与膀胱移行细胞癌的恶性组织学表型密切相关,可以作为评估该肿瘤恶性程度的分子标记之一。

The clinico-pathological significance of protein expression of PAK1 in bladder transitional cell carcinoma

OBJECTIVE: To investigate the protein expression of p21-activated kinase 1 gene (PAK1) in bladder transitional cell carcinoma (BTCC) and its clinico-pathological significance. METHODS: Immunohistochemistry and TUNEL were used, in combination with tissue microarray technique, to examine the protein expression of PAK1 and status of cell apoptosis in 100 BTCC tissue specimens obtained during operation and 30 specimens of adjacent normal bladder mucosa. RESULTS: All adjacent normal bladder mucosa specimens were negative in PAK1 protein expression or only with a low-level expression of PAK1 protein, while 58% of the BTCC specimens showed over-expression of PAK1. PAK1 expression was significantly associated with tumor pathological grade and tumor size (both P < 0.05). The PAK1 overexpression rate of the poorly-differentiated BTCC specimens (at the G3 stage) was 78%, significantly higher than that of the well-differentiated specimens (at the stage G1/G2, 47%, P = 0.05). The PAK1 overexpression rate of the large-sized BTCC specimens (>or= 3 cm in diameter) was 73%, significantly higher than that of the small-sized BTCC specimens (< 3 cm in diameter, P = 0.034). The PAK1 protein expression was negatively correlated with the apoptotic index of the cells (P < 0.05). CONCLUSION: Overexpression of PAK1 protein may via its anti-apoptotic function to play an important role in the development and progression of BTCC. Overexpression of PAK1 in BTCC is associated closely with tumor malignant histological phenotype and it may be used as a molecular marker to predicate the malignant potential of BTCC.