K-ras oncogene mutations indicate malignancy in cystic tumors of the pancreas

K-ras oncogene mutations indicate malignancy in cystic tumors of the pancreas
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DOI:
10.1097/00000658-199807000-00012
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发表时间:
1998-07-01
期刊:
影响因子:
9
通讯作者:
Rothmund, M
Rothmund, M
中科院分区:
医学1区
文献类型:
--
作者:
Bartsch, D;Bastian, D;Rothmund, M

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目的评价胰腺囊性肿瘤的临床参数、术前诊断试验、组织学表现和K-ras癌基因突变的存在,以确定哪种癌基因突变最能预测胰腺囊性肿瘤的恶性程度。方法对19例胰腺囊性肿瘤患者进行K-ras基因突变分析,包括聚合酶链式反应-限制性内切酶酶切分析和DNA直接测序,以筛选准确预测恶性程度的指标。结果所有胰腺恶性囊性肿瘤(5例囊腺癌和3例粘液腺癌)均存在K-ras基因突变,其中2例患者经皮细针抽吸物中也检测到K-ras基因突变。相反,9个良性囊腺瘤或实性乳头状肿瘤中没有K-ras突变。平均随访50个月后,携带K-ras野生型序列的良性肿瘤患者无一例复发。8例恶性囊性胰腺肿瘤中有7例在CT或内窥镜逆行胰胆管造影术中显示主胰管扩张,而11例良性肿瘤中无一例显示主胰管扩张。结论K-ras基因突变分析是判断囊性胰腺肿瘤手术前后恶性潜能的有力工具。在计算机断层扫描或内窥镜逆行胰胆管造影术中,主胰管扩张高度提示这些罕见肿瘤的恶性。
Objective To evaluate clinical parameters, presurgical diagnostic tests, histologic findings, and the presence of K-ras oncogene mutations in cystic tumors of the pancreas to determine which best predict malignancy.Summary Background Data Because presurgical, intraoperative, and final pathologic differentiation is difficult in cystic tumors of the pancreas, it would be a major benefit to identify markers that accurately predict malignancy in these rare tumors. The role of K-ras oncogene mutations as an indicator of malignancy has not been determined in these tumors.Methods Nineteen patients with cystic tumors of the pancreas were evaluated, including K-ras mutation analysis based on polymerase chain reaction and restriction digestion assays and direct DNA sequencing, to screen for parameters that accurately predict malignancy.Results All malignant cystic pancreatic tumors (five cystadenocarcinomas and three mucin-producing adenocarcinomas) harbored K-ras mutations at codon 12 or 13. K-ras mutations were also detected in the percutaneous fine-needle aspirates of two of these patients. In contrast, none of nine benign cystadenomas or the solid-papillary neoplasm had K-ras mutations. None of the patients with a benign tumor carrying K-ras wild-type sequences developed recurrent disease after a mean follow-up of 50 months. Seven of the 8 malignant cystic pancreatic tumors, but none of the 11 benign tumors, showed dilatation of the main pancreatic duct on computed tomography or endoscopic retrograde cholangiopancreatography.Conclusions K-ras mutation analysis seems to be a powerful tool to determine the malignant potential of cystic pancreatic tumors before and after surgery. Dilatation of the main pancreatic duct on computed tomography or endoscopic retrograde cholangiopancreatography is highly suggestive for malignancy in these rare tumors.