Reduced p21WAF1/CIP1 expression is an early event in gallbladder carcinogenesis and is of prognostic significance for patients with carcinomas of the gallbladder
Reduced p21WAF1/CIP1 expression is an early event in gallbladder carcinogenesis and is of prognostic significance for patients with carcinomas of the gallbladder
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DOI：
10.1053/hupa.2001.26474
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发表时间：
2001-08-01
期刊：
影响因子：
3.3
通讯作者：
Makuuchi, M
中科院分区：
文献类型：
--
作者：
Li, X;Hui, AM;Makuuchi, M
胆囊癌（GBC）发生和发展的分子基础仍然知之甚少。为探讨p21（WAF 1/CIP 1）和p53蛋白在胆囊癌发生中的作用及其对胆囊癌患者预后的意义，我们采用免疫组化方法检测了一系列手术切除标本中p21（WAF 1/CIP 1）和p53蛋白的表达，包括正常胆囊上皮、癌前病变、腺瘤、不典型增生和胆囊癌。p21（WAF 1/CIP 1）表达减少常见于癌（18/37; 49%），甚至癌前病变腺瘤（37; 43%）和发育不良（5/5; 100%）。p53过表达率分别为43%的腺瘤、60%的不典型增生和57%的腺癌。GBC中p21（WAF 1/CIP 1）和p53表达呈负相关（P = 0.01）。生存分析表明，p21（WAF 1/CIP 1）表达减少与II期至IV期GBC患者的无病生存期和总生存期缩短显著相关（分别为P= 0.04和0.03）。这些观察结果表明，减少p21（WAF 1/CIP 1）的表达和p53的过度表达有助于GBC的早期阶段和手术切除标本中的p21（WAF 1/CIP 1）表达的测定将增加预后信息的常规病理检查晚期GBC患者。《人文哲学》32：771-777。(C)2001年，W.B.桑德斯公司
The molecular basis underlying the development and progression of gallbladder carcinoma (GBC) remains poorly understood. To evaluate the roles of p21(WAF1/CIP1) and p53 in gallbladder carcinogenesis and to assess their prognostic significance for patients with GBC, we used immunohistochemistry to examine the expression of p21(WAF1/CIP1) and p53 protein in a series of surgically resected specimens, including normal epithelia, precancerous lesions adenoma, and dysplasia, and carcinomas of the gallbladder. Reduced p21(WAF1/CIP1) expression was frequently observed in carcinomas (18 of 37 lesions; 49%), and even in precancerous lesions adenomas (3 of 7; 43%) and dysplasias (5 of 5; 100%). p53 overexpression was detected in 43% of the adenomas, 60% of the dysplasias and 57% of the carcinomas. There was an inverse relationship between p21(WAF1/CIP1) and p53 expression in GBCs (P =.01). Survival analysis indicated that reduced p21(WAF1/CIP1) expression was significantly associated with shortened disease-free and overall survival (P=.04 and .03, respectively) for patients with stages II to IV GBCs. These observations suggest that reduced p21(WAF1/CIP1) expression and p53 overexpression contribute to GBC from an early stage and that determination of p21(WAF1/CIP1) expression in surgically resected specimens would add prognostic information to conventional pathologic examinations for patients with advanced-stage GBC. HUM PATHOL 32: 771-777. (C) 2001 by W.B. Saunders Company.