K-ras mutation in focal proliferative lesions of human pancreas.
K-ras mutation in focal proliferative lesions of human pancreas.
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发表时间：
1998-06
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通讯作者：
P. G. Terhune;Dawnyale M. Phifer;T. Tosteson;D. Longnecker
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作者：
P. G. Terhune;Dawnyale M. Phifer;T. Tosteson;D. Longnecker
K-ras基因在≥ 75%的人胰腺癌和许多非癌患者的增生性导管病变中发生突变。在这项研究中，K-ras基因突变的发生率确定在一个频谱局灶性胰腺增生性病变，以评估其癌前的意义。基于PCR的突变富集RFLP分析用于鉴定密码子12中的突变。还进行Ki 67和p53的免疫染色。47%的导管内非乳头状增生（8/17）含有密码子12突变，55%的腺瘤样增生（6/11）也含有密码子12突变。在乳头状增生（44例中的27例）中，这一比率增加到61%，在严重异型增生（9例中的7例）中，这一比率增加到78%。Ki 67增殖标记物染色的细胞分数显示与K-ras突变率一般相关。p53蛋白的核染色仅见于两个具有严重异型增生的导管病变。在正常腺泡组织（n = 38）、鳞状化生（n = 13）、导管复合体（n = 8）或局灶性腺泡细胞发育不良（n = 5）中未发现突变。在导管病变中，K-ras基因突变的存在似乎与增殖潜能有普遍的相关性。然而，由于K-ras基因突变的病变的高患病率，我们得出结论，这种突变本身不能作为进展为癌症的重大风险的证据。试图利用存在的K-ras突变的DNA收集从胰液或十二指肠吸出物作为一种方法来诊断隐匿性胰腺癌似乎容易受到高假阳性率。
The K-ras gene is mutated in > or =75% of human pancreatic adenocarcinomas and in a number of hyperplastic ductal lesions from noncarcinoma patients. In this study, the incidence of K-ras mutation was determined in a spectrum of focal proliferative pancreatic lesions to evaluate their preneoplastic significance. PCR-based mutation-enriched RFLP analysis was used to identify mutations in codon 12. Immunostaining for Ki67 and p53 was also performed. Forty-seven % of intraductal nonpapillary hyperplasias (8 of 17) contained codon 12 mutations, as did 55% of adenomatoid hyperplasias (6 of 11). This rate increased to 61% in papillary hyperplasias (27 of 44) and to 78% when there was severe dysplasia (7 of 9). The fraction of cells staining for the Ki67 proliferation marker showed a general correlation with the rate of K-ras mutation. Nuclear staining for p53 protein was seen only in two ductal lesions with severe dysplasia. No mutations were found in normal acinar tissue (n = 38), squamous metaplasia (n = 13), ductal complexes (n = 8), or focal acinar cell dysplasia (n = 5). There seemed to be a general correlation of proliferative potential with the presence of K-ras mutation in ductal lesions. However, because of the high prevalence of lesions with K-ras mutations, we conclude that this mutation alone cannot be taken as proof of significant risk for progression to carcinoma. Efforts to use the presence of K-ras mutations in DNA harvested from pancreatic juice or duodenal aspirates as an approach for diagnosis of occult pancreatic carcinoma seem vulnerable to a high false-positive rate.