慢性胰腺炎K-ras基因突变的临床病理学意义

Clinicopathological Significance of K - ras Point Mutation at Codon 12 in Chronic Pancreatitis

目的 :探讨慢性胰腺炎K ras基因突变的临床病理学意义。方法 :9例手术切除的慢性胰腺炎的石蜡标本 ,用微解剖法分离慢性胰腺炎的胰导管上皮粘液细胞增生灶 ,提取、扩增DNA ,用ASO斑点杂交检测K ras基因第 12密码子的碱基序列。对 9例接受手术治疗的病人进行长期随访。结果 :9例慢性胰腺炎中 4例有明显的胰导管上皮粘液细胞增生 ,其中 2例被检出GAT型突变 ,分别占全组和有胰管上皮粘液细胞增生的 2 2 %和 5 0 %。两个突变病例分别是接受了胰体尾切除和胰头十二指肠切除手术 ,术后分别随访 17年和 10年 ,没有发现任何恶变迹象。结论 :慢性胰腺炎可以检出K ras基因突变 ;发生了K ras基因突变的慢性胰腺炎上皮粘液细胞增生灶 ,未必一定发生为胰腺癌 ;胰液、粪便、末梢血液和尿液的检测 ,以及胰腺组织细针穿刺液检出K ras基因突变 ,对胰腺癌的诊断有重要参考价值 ,但不应视为胰腺癌的确诊依据。

Objective: The aim of this study was to evaluate the clinicopathological significance of a follow up of postpancreatectomy patients with chronic pancreatitis and K ras mutations at codon 12. Methods: Paraffin embedded specimens of 9 patients with resected chronic pancreatitis were involved in this study. We used microdissected method to separate the lesions of mucous cell hyperplasias of pancreatic duct. K ras point mutations were examined by ASO method after performing DNA extraction and amplication by PCR. Extensive clinicopathologic and follow up data on all patients were evaluated . Results: K ras point mutations were detected in 2 cases (22%) of 9 chronic pancreatitis, and 50% of 4 cases with mucous cell hyperplasias of pancreatic duct. The mutations of the K ras codon 12 were of the same type: GGT (glycine) to GTT (valine), in which the patients were subjected to distal pancreatectomy and the whipple procedure, respectively. Seventeen and 10 years follow up showed that the patients were still alive without any indication of cancer. Others were all wild type GGT. Conclusion: The K ras point mutations could be detected in chronic pancreatitis. Presence of a K ras gene mutation in chronic pancreatitis is not sign or represents an increased risk of developing pancreatic cancer. The K ras point mutation detections in pancreatic juice, stool, peripheral blood, urine, and fine needle aspiration cytologic specimens of pancreatic tissues may be of great diagnostic value in pancreatic cancer, but they can not be used as evidences for final diagnosis.