Rijken A M, van Gulik T M, Polak M M, Sturm P D, Gouma D J, Offerhaus G J
Department of Surgery, Academic Medical Center, University of Amsterdam, The Netherlands.
J Surg Oncol. 1998 Jul;68(3):187-92. doi: 10.1002/(sici)1096-9098(199807)68:3<187::aid-jso11>3.0.co;2-z.
The K-ras gene is one of the most extensively investigated oncogenes in a wide variety of human tumors, but has rarely been studied in distal bile duct carcinoma (DBDC). We sought to investigate the diagnostic and prognostic value of K-ras codon 12 mutations in this type of tumor.
Forty-seven patients who had undergone resection for DBDC were analyzed to reveal the incidence of K-ras codon 12 mutations, the locus most frequently involved. A rapid and simple two-step, semi-nested polymerase chain reaction (PCR) technique was used to detect mutations in paraffin-embedded tumor samples.
The PCR mismatch amplification technique demonstrated that 35 (75%) of the 47 tumors harbored a point mutation in codon 12 of the K-ras oncogene. Patients with mutated tumors had no statistically different survival time compared to those patients without a mutation in the tumor. In contrast, negative microscopic margins proved to be a significant prognosticator.
K-ras codon 12 mutations are common in DBDC and may be useful in the diagnosis and early detection of these tumors. However, no prognostic value of these mutations could be identified in this analysis. The results of this study also suggest that negative surgical margins remain the mainstay of prognostication in resectable DBDC. However, due to the small number of patients included in this study, the results obtained should be interpreted with care.
K-ras基因是在多种人类肿瘤中研究最为广泛的癌基因之一，但在远端胆管癌（DBDC）中的研究却很少。我们试图研究K-ras密码子12突变在这类肿瘤中的诊断和预后价值。
对47例行DBDC切除术的患者进行分析，以揭示K-ras密码子12突变（最常涉及的位点）的发生率。采用一种快速简单的两步半巢式聚合酶链反应（PCR）技术检测石蜡包埋肿瘤样本中的突变。
PCR错配扩增技术显示，47例肿瘤中有35例（75%）在K-ras癌基因的密码子12处存在点突变。肿瘤发生突变的患者与肿瘤未发生突变的患者相比，生存时间无统计学差异。相比之下，显微镜下切缘阴性被证明是一个重要的预后指标。
K-ras密码子12突变在DBDC中很常见，可能有助于这些肿瘤的诊断和早期检测。然而，在本分析中未发现这些突变具有预后价值。本研究结果还表明，手术切缘阴性仍然是可切除DBDC预后的主要指标。然而，由于本研究纳入的患者数量较少，所得结果应谨慎解读。
