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，以鉴别诊断胆道良恶性病变的肿瘤性和非肿瘤性病变。作为这一目的的基础研究，我们对Vater乳头癌的分子生物学特性进行了研究。方法检测乳头状癌组织中P53、p21/Waf1的表达及K-ras密码子12突变情况。本文对37例Vater乳头癌进行了研究。肉眼可见溃疡性癌15例，非溃疡性癌22例。组织学类型：肠型9例，胰胆管型27例，未分化1例。福尔马林固定的石蜡包埋切片用免疫组织化学方法检测p53和p21的表达。采用聚合酶链式反应-限制性片段长度多态性两步法检测K-ras基因第12密码子突变，并进行直接测序。37例中有17例(46%)P53过度表达，溃疡型高于非溃疡型(67%vs.32%，p&lt；0.05)。P21/WAFI蛋白表达阳性率为41%(15/37)，与P53蛋白表达无相关性。K-ras基因第12密码子突变在37例中有14例(38%)，肠型明显高于胆胰型(66%vs.30%，p&lt；0.05)。在直接测序中，突变主要为GGT到GAT(9/14)和GGT到GTT(4/14)。突变类型与组织学类型无关。在Vater乳头状癌中，P53的过表达可能在肿瘤溃烂中起一定作用。P21/waft的表达是通过不依赖于p53的途径诱导的。肠型和胆胰型癌可能通过不同的机制发生，K-ras基因突变主要与肠型有关。

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.