【关键词】 胆囊腺瘤；胆囊癌；P16基因；免疫组化
To study the expression of p16 protein and discuss its clinical significance in benign and malignant gallbladder tumors
【Abstract】 Objective To discuss the expression of p16 protein and its clinical pathological characteristics in the benign and malignant gallbladder tumors. Methods p16 protein was detected in 46 cases of gallbladder carcinoma, 20 cases of gallbladder adenoma, 24 cases of normal gallbladder mucosa with immunohistochemical Envision. Results The positive rates of p16 protein were 53.0%, 90.0% and 92.1% in gallbladder carcinoma, gallbladder adenoma, normal gallbladder mucosa respectively. The positive rate of p16 protein in gallbladder carcinoma was higher than those in gallbladder adenoma and normal gallbladder mucosa (P<0.05). The positive rate of p16 protein in low differentiation group was significantly lower than those in middle and high differentiation groups in gallbladder carcinoma (P<0.05). The positive rate of p16 protein in S4-S5 phase was significantly lower than those in S1-S2 phase in gallbladder carcinoma (P<0.05). Conclusions The expression of p16 protein was related to benign or malignant, pathological types, differentiation and Nevin phase in gallbladder tumors. P16 protein may be an indication of diagnosis and prognosis in gallbladder carcinoma.
【Key words】 gallbladder adenoma； gallbladder carcinoma； p16 protein； immunohistochemistry
P16基因是多重肿瘤的抑制基因（MTS1），位于人类染色体qp21区位上，全长为8.5kb,其编码分子量为15.84kD的蛋白质P16，P16基因是一种CDKS抑制蛋白基因，其表达蛋白通过与CDK4的特异的结合来抑制该蛋白激活酶的活性，阻止细胞从G1期到S期，从而抑制细胞增殖［1］。当其发生突变或缺失时，调控细胞周期的抑制因子P16不能正常表达，导致细胞增殖失控，而发生肿瘤形成［2］。本文探讨其P16蛋白表达与胆囊肿瘤的发生、发展关系及临床病理特征。
1 材料与方法
1．1 材料
由上海市瑞金医院集团闵行医院病理科提供2001年1月～2005年12月外科手术存档蜡块标本，胆囊癌46例，其中乳头状腺癌16例，管状腺癌24例，粘液腺癌6例。胆囊腺瘤20例。对照组胆囊正常黏膜24例。所有病例均经HE染色病理诊断证实。
1．2 方法
石蜡存档标本分别切片，厚4μm,分别作免疫组化既用型二步法染色。用已知的阳性切片作阳性对照。P16蛋白的阳性表达定位于细胞浆或细胞核内呈棕黄色颗粒。阳性细胞数的细胞核或浆有棕色＜25%及无着色为（-）；阳性细胞数在25%～50%为（ ）；阳性细胞数＞50%为（ ）。
1.3 统计学方法