DNA Content and Gene Expression in Adenoma－Carcinoma Sequence of Gallbladder Carcinogenesis（胆囊腺瘤－腺癌中的DNA含量和基因表达）

摘要

目的 研究胆囊腺瘤从增殖到恶变中腺上皮细胞的增殖变化和基因表达。方法 用PCR-RFLP法测定APC、ras基因突变，ABC免疫化学组织染色法测定p53蛋白表达。用TJTY-300全自动图像分析仪测定胆囊上皮细胞核异型性和DNA含量。结果 上皮细胞核异型性和DNA含量在胆囊腺瘤-腺癌过程中逐渐增加。胆囊腺瘤中异倍体比例与腺瘤的大小有明显的关系，直径≥1cm异倍体显著增加(P<0．05)。在胆囊腺瘤-腺癌过程中可检测到APC基因和RAS基因突变。P53蛋白在这一过程中不表达。结论 胆囊腺瘤-腺癌的过程是胆囊癌发生中一条重要的途径。当胆囊腺瘤直径≥1cm时具有明显的癌变潜能。其分子改变机制与胆囊上皮不典型增生-原位癌途径不同。Objective To study the proliferative changeof epithelium and gene expression in adenoma-carcinoma sequence of gallbladder carcinogenesis.Methods Mutations of K-ras gene and APC gene were detected by PCR-RFLP, and the expression of p53 protein was detected by ABC immunohistochemistry. DNA contents were detected by using a TJTY-300 automatic image analyzer. Results Cell DNA contents and atypia were increased gradually in the adenoma-carcinoma sequence of gallbladder. Aneuploidy in gallbladder adenoma was associated with the size of adenoma. When the diameter of adenoma was more than 1 cm, the aneuploidy was significantly increased (P < 0.05 ). APC gene and K-ras gene mutations were detected in the adenoma-carcinoma pathway.And p53 protein overexpression was not detected in this pathway. Conclusion Adenoma-carcinoma sequence pathway plays an important role in gallbladder carcinogenesis. Gallbladder adenoma has an obvious tendency to malignant transformation, especially in the patients with adenoma of 1 cm in diameter or above. It has molecular abnormalities different from those de novo carcinomas.