Castells A, Puig P, Móra J, Boadas J, Boix L, Urgell E, Solé M, Capellà G, Lluís F, Fernández-Cruz L, Navarro S, Farré A
Institut Clínic de Malalties Digestives and Department of Pathology, Hospital Clínic i Provincial, University of Barcelona, Catalonia, Spain.
J Clin Oncol. 1999 Feb;17(2):578-84. doi: 10.1200/JCO.1999.17.2.578.
Previous studies have demonstrated the presence of K-ras mutations in the plasma of patients with pancreatic carcinoma. However, the diagnostic utility and the prognostic significance of this finding have never been addressed.
Forty-four consecutive patients with histologically confirmed primary pancreatic ductal adenocarcinoma were included. A control group of 37 patients with chronic pancreatitis, 10 patients with other tumors of the pancreatic area, nine patients with acute pancreatitis, and four healthy volunteers was also included. Plasma DNA was isolated and K-ras codon-12 mutations were analyzed by means of restriction fragment length polymorphism-polymerase chain reaction and single-strand conformation polymorphism techniques. Patients were followed up to establish their clinical outcome.
The mutant-type K-ras gene was found in plasma DNA samples of 12 (27%) of 44 patients with pancreatic ductal adenocarcinoma; this finding was related to the tumor stage (P = .05), mainly in the presence of distant metastases (P = .02). In addition, K-ras mutations were detected in the plasma DNA of two (5%) of 37 patients with chronic pancreatitis. In the subset of patients with pancreatic masses, the sensitivity and specificity of plasma K-ras analysis for pancreatic adenocarcinoma were 27% and 100%, respectively. Finally, pancreatic carcinoma patients with the mutant-type K-ras gene in plasma DNA exhibited a shorter survival time than patients with the wild-type gene (P<.005), and plasma K-ras mutations were identified as the only independent prognostic factor (odds ratio, 1.51; 95% confidence interval, 1.02 to 2.23).
Plasma K-ras analysis is a highly specific, low-sensitivity approach that has diagnostic and prognostic clinical implications in patients with pancreatic carcinoma.
既往研究已证实在胰腺癌患者的血浆中存在K-ras基因突变。然而，这一发现的诊断效用及预后意义从未得到探讨。
纳入44例经组织学确诊的原发性胰腺导管腺癌患者。还纳入了一个对照组，其中包括37例慢性胰腺炎患者、10例胰腺区域其他肿瘤患者、9例急性胰腺炎患者及4名健康志愿者。分离血浆DNA，并采用限制性片段长度多态性聚合酶链反应和单链构象多态性技术分析K-ras密码子12突变。对患者进行随访以确定其临床结局。
在44例胰腺导管腺癌患者的血浆DNA样本中，有12例（27%）检测到突变型K-ras基因；这一发现与肿瘤分期相关（P = 0.05），主要见于存在远处转移的患者（P = 0.02）。此外，在37例慢性胰腺炎患者的血浆DNA中，有2例（5%）检测到K-ras突变。在胰腺肿块患者亚组中，血浆K-ras分析对胰腺腺癌的敏感性和特异性分别为27%和100%。最后，血浆DNA中存在突变型K-ras基因的胰腺癌患者的生存时间短于野生型基因患者（P<0.005），血浆K-ras突变被确定为唯一的独立预后因素（优势比，1.51；95%置信区间，1.02至2.23）。
血浆K-ras分析是一种高特异性、低敏感性的方法，对胰腺癌患者具有诊断和预后的临床意义。
