【摘要】 目的研究胆囊腺癌、癌旁组织、腺瘤性息肉和慢性胆囊炎组织中葡萄糖调节蛋白78(GRP78)和94(GRP94)蛋白表达水平及其临床病理意义。方法应用EnVisionTM免疫组化法检测108例胆囊腺癌、46例癌旁组织、15例腺瘤性息肉和35例慢性胆囊炎组织中GRP78和GRP94蛋白的表达;分析两者表达与胆囊腺癌临床病理特征的相关性及患者生存期的关系。结果胆囊腺癌中GRP78和GRP94蛋白表达明显高于癌旁组织、腺瘤性息肉和慢性胆囊炎(P<0.01);GRP78和/或GRP94蛋白阳性表达的良性病变胆囊上皮呈不同程度非典型增生。高分化腺癌、淋巴结未转移及未侵犯周围组织器官病例GRP78和GRP94蛋白表达明显低于低分化腺癌、淋巴结转移及侵犯周围组织器官病例(P<0.05或P<0.01)。Kaplan-Meier单因素生存分析显示GRP78(P=0.009)或GRP94(P=0.022)蛋白阳性表达与生存期减少密切相关,Cox回归多因素因素分析显示GRP78(P=0.014)或GRP94(P=0.020)蛋白阳性表达是胆囊腺癌预后不良的独立评估指标。结论 GRP78和GRP94蛋白表达水平可能是反映胆囊腺癌发生发展、临床生物学行为及预后的重要标记物,检测胆囊腺癌中GRP78和GRP94蛋白表达水平可能对指导临床辅助治疗有重要临床价值。此外,检测胆囊良性病变组织中GRP78和GRP94蛋白表达水平对早期发现胆囊腺癌可能有较重要的临床意义。更多还原

【Abstract】 【Objective】To study the expression levels of GRP78 and GRP94 and their clinicopathological significances in the adenocarcinoma,peritumoral tissues,adenomatous polyp and chronic cholecystitis of gallbladder.【Methods】 EnVisionTM immunohistochemistry for detecting expressive levels of GRP78 and GRP94 was used in the tissues of gallbladder adenocarcinoma(n =108),peritumoral tissues(n =46),adenomatous polyp(n =15) and chronic cholecystitis(n =35);The relevance of the two elements and clinicopathological features and survival time of patients of gallbladder adenocarcinoma was analyzed.【Results】 The positive frequencies of GRP78 and GRP94 were significantly higher in adenocarcinoma than that in peritumoral tissues,adenomatous polyp and chronic cholecystitis(P <0.01).The positive cases of GRP78 and/or GRP94 in the benign lesions showed moderate-or severedysplasia of gallbladder epithelia.The positive rates of GRP78 and GRP94 were significantly lower in well-differentiated adenocarcinoma,no-metastasis of lymph node and no-invasiveness of regional tissues than those in moderate-ly or poorly-differentiated adenocarcinoma,metastasis of lymph node and invasiveness of regional tissues(P <0.05 or P <0.01).Unitivariate Kaplan-Meier analysis showed that increased expression of GRP78(P =0.009) or GRP94(P =0.022) was associated with decreased overall survival.Multivariate Cox regression analysis showed that increased expression of GRP78(P =0.014) or GRP94(P =0.020) was an independent prognostic predictor in gallbladder adenocarcinoma.【Conclusions】 The expression levels of GRP78 and/or GRP94 might be important markers for reflecting the carcinogenesis,progression and biological behaviors and prognosis of gallbladder adenocarcinoma.The assays of GRP78 and/or GRP94 expressive levels might have important clinical values for guiding auxiliary therapy of gallbladder adenocarcinoma.Additional,the detection of GRP78 and/or GRP94 expressive levels in the benign lesions might have clinical significances on finding of gallbladder adenocarcinoma in the early stage.更多还原