【摘要】 目的检测胃肠道癌组织中Parafibromin蛋白的表达,并探讨其与临床病理特征和预后的关系。方法选取1997年12月—2008年12月日本富山大学医学部手术切除并经病理证实为胃肠道癌的患者814例。收集所有胃肠道癌患者癌组织标本814份,同时收集胃肠道癌患者癌旁组织标本328份及腺瘤组织标本129份。采用免疫组织化学法检测胃肠道癌组织、癌旁组织和腺瘤组织中Parafibromin蛋白的表达情况;并对胃肠道癌患者进行生存分析和死亡危险因素的Cox回归分析。结果 Parafibromin蛋白表达阳性率在胃肠道癌组织中为48.9%(398/814),低于腺瘤组织及癌旁组织的78.3%(101/129)和92.7%(304/328),差异有统计学意义(χ2=189.20、47.50,P<0.05)。Spearman等级相关分析显示,Parafibromin蛋白表达阳性与肿瘤直径、淋巴管侵袭、淋巴结转移、UICC分期呈负相关(rs=-0.198、-0.134、-0.238、-0.244,P<0.05),与性别、年龄、静脉侵袭无相关性(rs=0.055、0.039、-0.048,P>0.05)。电话随访573例胃肠道癌患者,失访241例,生存时间为0.2~146.4个月,平均42.1个月。生存分析显示,Parafibromin蛋白表达阴性患者累积生存率低于Parafibromin蛋白表达阳性患者(χ2=32.60,P<0.05)。Cox回归分析显示,年龄≥60岁〔OR(95%CI)=1.589(1.194,2.113)〕、肿瘤直径≥4.5 cm〔OR(95%CI)=1.407(1.037,1.908)〕、有淋巴管侵袭〔OR(95%CI)=1.925(1.445,2.565)〕、有淋巴结转移〔OR(95%CI)=2.621(1.867,3.679)〕、UICC分期Ⅲ~Ⅳ期〔OR(95%CI)=1.564(1.067,2.292)〕是胃肠道癌死亡的独立危险因素(P<0.05),而Parafibromin蛋白表达阳性〔OR(95%CI)=0.611(0.463,0.806)〕是胃肠道癌死亡的保护因素(P<0.05)。结论 Parafibromin蛋白表达降低与胃肠道癌的发生、侵袭和转移有关,且与胃肠道癌患者的预后密切相关,Parafibromin蛋白可作为潜在的胃肠道癌预后指标,为今后的临床研究提供参考价值。更多还原

【Abstract】 Objective To clarify the roles of parafibromin expression and the correlation with aggressive features and prognosis of gastrointesitnal carcinomas. Methods From December 1997 to December 2008 selected 814 Patients with gastrointestinal cancer in Japan Toyama University Faculty of Medicine. It was examined by immunohistochemistry on tissue microarray containing gastrointestinal carcinomas( n = 814),adenomas( n = 129) and non- neoplastic mucosa( n = 328) with a comparison of its expression with clinicopathological parameters,and conducted survival analysis and risk factors for death Cox regression analysis. Results Parafibromin expression was localized in the nucleus of gastrointesitnal epithelial cells,adenoma and carcinoma cells. Its expression was gradually decreased from non- neoplastic mucosa to carcinoma,through adenomas( χ2= 189. 20,47. 50; P < 0. 05) and negative correlation with tumour size,lymphatic invasion,lymph node metastasis and Union Internationale Contrele Cancer( UICC) staging( rs=- 0. 198,- 0. 134,- 0. 238,- 0. 244; P < 0. 05),but not with sex,age or venous invasion( rs= 0. 055,0. 039,- 0. 048; P > 0. 05). Telephone follow- up of 573 cases of gastrointestinal cancer patients,lost 241 cases,survival time was 0. 2 to 146. 4 months,an average of 42. 1 months. Survival analysis showed cumulative survival rate of patients with positive Parafibromin expression to be higher than without its expression( χ2= 32. 60,P < 0. 05).Cox regression analysis showed that age≥60 years 〔OR( 95% CI) = 1. 589( 1. 194,2. 113) 〕,tumor size≥4. 5 cm 〔OR( 95%CI) =1.407( 1.037,1. 908) 〕,lymphatic invasion 〔OR( 95%CI) =1.925( 1. 445,2. 565) 〕,lymph node metastasis 〔OR( 95% CI) = 2. 621( 1. 867,3. 679) 〕,UICC staging Ⅲ to Ⅳ 〔OR( 95% CI) = 1. 564( 1. 067,2. 292) 〕venous invasion were independent prognostic factors for carcinomas( P < 0. 05). Positive expression of Parafibromin protein in〔OR( 95%CI) =0. 611( 0. 463,0. 806) 〕were protective factors of death of gastrointestinal cancer( P <0. 05). Conclusion Down- regulated Parafibromin expression possibly contributes to pathogenesis,growth,invasion and metastasis of gastrointestinal and might be considered as a promising marker to indicate the aggressive behaviors and prognosis of gastrointesitnal carcinomas.更多还原