Shibata D, Almoguera C, Forrester K, Dunitz J, Martin S E, Cosgrove M M, Perucho M, Arnheim N
Department of Pathology, Los Angeles County USC Medical Center 90033.
Cancer Res. 1990 Feb 15;50(4):1279-83.
Formalin-fixed paraffin-embedded tissue specimens obtained by fine needle aspiration of pancreatic masses from 47 patients were examined retrospectively for cytology and the presence of mutant c-K-ras oncogenes. Point mutations of c-K-ras in codon 12 were detected by RNA-DNA RNAse A mismatch cleavage after in vitro DNA amplification of the cellular c-K-ras sequences by the polymerase chain reaction. Of the 36 patients with pancreatic adenocarcinoma, mutant c-K-ras oncogenes were detected in 18 of 25 (72%) with malignant cytologies, 2 of 8 (25%) with atypical cytologies, and 0 of 3 with benign aspiration cytologies. The remaining 11 patients without pancreatic adenocarcinomas did not have mutant c-K-ras genes detectable by the assay. The diagnosis of pancreatic adenocarcinoma was based upon clinical follow-up. The presence of mutant c-K-ras oncogenes did not significantly affect survival in the patients studied. Mutant c-K-ras genes were found at the time of initial clinical presentation in the majority of pancreatic adenocarcinomas, suggesting an important role of the mutation in oncogenesis. In conjunction with cytology, our approach represents an application for cancer diagnosis at the molecular genetic level.
对47例患者经细针穿刺胰腺肿块获取的福尔马林固定石蜡包埋组织标本进行回顾性细胞学检查及突变型c-K-ras癌基因检测。通过聚合酶链反应对细胞c-K-ras序列进行体外DNA扩增后，采用RNA-DNA RNA酶A错配切割法检测c-K-ras第12密码子的点突变。在36例胰腺腺癌患者中，25例恶性细胞学检查结果者中有18例（72%）检测到突变型c-K-ras癌基因，8例非典型细胞学检查结果者中有2例（25%）检测到，3例良性穿刺细胞学检查结果者中未检测到。其余11例无胰腺腺癌的患者未检测到可通过该检测方法发现的突变型c-K-ras基因。胰腺腺癌的诊断基于临床随访。突变型c-K-ras癌基因的存在对所研究患者的生存无显著影响。大多数胰腺腺癌在初次临床表现时就发现有突变型c-K-ras基因，提示该突变在肿瘤发生中起重要作用。结合细胞学检查，我们的方法代表了分子遗传学水平在癌症诊断中的应用。
