molecular biological characteristics of carcinoma of the papilla of Vater

目标。本研究的目的是对胆汁进行分子生物学研究，以鉴别胆道的肿瘤和非肿瘤病变，以及胆道的良性和恶性病变。作为这一目的的基础研究，我们对水乳头癌的分子生物学特性进行了研究。研究了乳突癌组织中p53、p21/Waf1的表达及K-ras密码子12的突变。本文对37例水乳头癌进行了研究。镜下15例为溃疡性癌，22例为非溃疡性癌。组织学上肠型9例，胰胆型27例，未分化1例。用福尔马林固定、石蜡包埋切片，免疫组织化学染色检测p53和p21。采用两步聚合酶链反应-限制性片段长度多态性法检测K-ras密码子12突变，然后直接测序。37例患者中有17例（46%）发现P53过表达，溃疡型高于非溃疡型（67%比32%，p<0.05）。37例患者中有15例（41%）出现p21/Wafi蛋白表达，与p53无相关性。K-ras密码子12突变在37例中有14例（38%），肠型高于胰胆型（66%比30%，p<0.05）。直接测序结果显示，突变主要为GGT - GAT（9/14）和GGT - GTT（4/14）。突变类型与组织学类型无关。在水乳头癌中，p53过表达可能在肿瘤溃烂中起作用。p21/Waft的表达是通过p53非依赖性途径诱导的。肠型和胰胆道型的癌可能通过不同的机制发生，K-ras突变主要与肠型相关。

Objectives. The aim of this study is to perform molecular biological investigation of the bile for differential diagnosis of tumorous and non-tumorous lesions, and of benign and malignant lesions of the biliary tract. As the basic study of this aim, we studied on the molecular biological characteristics of carcinoma of the papilla of Vater. p53 and p21/Waf1 expression and K-ras codon 12 mutation in carcinoma of the papilla of Vater were investigated.Methods. Thirty seven' cases of carcinoma of the papilla of Vater were studied. Macroscopically, the carcinoma was ulcerative in 15 cases and non-ulcerative in 22 cases. Histologically, nine were intestinal type, 27 were pancreaticobiliary type, and one was undifferentiated. Formalin-fixed, paraffin-embedded sections were immunohistochemically stained for p53 and p21. K-ras codon 12 mutation was detected with the two-step polymerase chain reaction-restriction fragment length polymorphism method followed by direct sequencing.Results. p53 overexpression was found in 17 of 37 cases (46%) and was more frequent in the ulcerative type than in the non-ulcerative type (67% vs. 32%, p<0.05). p21/Wafi protein expression was found in 15 of 37 cases (41%), and was not correlated with that of p53. K-ras codon 12 mutation was found in 14 of 37 cases (38%), and was more frequently detected in the intestinal type than in the pancreaticobiliary type (66% vs. 30%, p<0.05). On direct sequencing, the mutations were mainly GGT to GAT (9/14) and GGT to GTT (4/14). The type of mutation did not correlate with the histological type.Conclusions. In carcinoma of the papilla of Vater, p53 overexpression may play a role in tumor ulceration. p21/Waft expression is induced via a p53-independent pathway. Carcinomas of the intestinal and pancreaticobiliary types may develop via different mechanisms, and K-ras mutation is mainly associated with the intestinal type.