膀胱移行细胞癌中成纤维细胞生长因子3基因表达与扩增的临床意义

目的探讨膀胱移行细胞癌中成纤维细胞生长因子3（FGF3）基因的表达与扩增及其临床病理学意义。方法运用免疫组化和荧光原位杂交方法,结合组织芯片技术,检测FGF3在100例膀胱移行细胞癌和30例癌旁正常膀胱黏膜组织中的表达与扩增情况,结合肿瘤的临床病理学资料,分析它们之间的相关性。结果免疫组化结果显示,全部正常膀胱黏膜组织均呈FGF3蛋白阴性反应;在89例有效检测的膀胱移行细胞癌中,有20例（22％）出现FGF3阳性表达,而且明显多见于分化程度低（G3级）、浸润中晚期（T2-4期）或瘤体直径≥3cm的肿瘤（均P〈0．05）。本组FISH检测发现,在63例有效膀胱移行细胞癌中,有10例（16％）被检测到FGF3基因扩增,而且与肿瘤的大小和临床分期均有显著的相关性（均P〈0．05）。另外,10例FGF3基因扩增的膀胱癌均呈FGF3蛋白阳性表达;而剩下的53例无FGF3扩增的肿瘤中,只有3例（6％）出现FGF3蛋白阳性反应。结论FGF3蛋白在膀胱移行细胞癌中的表达上调与该肿瘤的恶性临床病理学表型密切相关,可能参与了部分肿瘤的恶性发展进程;膀胱移行细胞癌中FGF3基因扩增是其编码的FGF3蛋白表达上调的主要机制。

The clinical significance of expression and amplification of FGF3 in bladder transitional cell carcinoma

OBJECTIVE: To investigate the amplification and expression of FGF3 in bladder transitional cell carcinoma (BTCC) and its clinical significance. METHODS: Immunohistochemistry (IHC) and Fluorescence In Situ Hybridization (FISH) methods were used to examine the protein expression and amplification of FGF3 in a tissue microarray (TMA) of 100 BTCCs and 30 adjacent normal bladder mucosas, so as to analyze their correlation and association with patient's clinico-pathological features. RESULTS: In this study, none of the normal bladder mucosas were detected FGF3 positivity, while in 89 informative BTCCs, 20 (22%) cases were observed positive expression of FGF3 protein, and it was significantly more frequently to occur in BTCCs of poor-differentiation (Grade 3), later clinical stage (T2-4) and tumor in >or= 3 cm in diameter (P < 0.05). In FISH study, 10 of the 63 (16%) informative BTCCs were observed amplification of FGF3 and it was significantly associated with BTCC's tumor size and clinical stage (P < 0.05). In addition, 10 BTCCs with amplification of FGF3 in this study were all detected positive expression of FGF3 protein, while in the remaining 53 BTCCs without amplification of FGF3, only 3 (6%) cases were observed FGF3 protein positivity. CONCLUSION: The up-regulated expression of FGF3 in BTCC was associated closely with tumor's malignant clinical phenotypes, and it might be involved in the malignant progression of parts of BTCC. The amplification of FGF3 gene might be a predominant mechanism of increased expression of FGF3 protein in BTCC.