Tamagawa E, Ueda M, Takahashi S, Sugano K, Uematsu S, Mukai M, Ogata Y, Kitajima M
Departments of Surgery and Diagnostic Pathology, Keio University, School of Medicine, Tokyo 160, Japan.
Clin Cancer Res. 1997 Nov;3(11):2143-9.
K-ras point mutations have been observed in approximately 90% of pancreatic carcinomas. We genetically analyzed cases of pancreatic regional lymph nodal and plexus micrometastases in invasive ductal carcinoma of the pancreas who were node negative or had metastases limited histopathologically to pancreaticoduodenal lymph nodes. These cases underwent curative resection in our institute. The utility of genetic analysis was compared with that of histopathological study, in terms of postoperative clinical outcome, as a predictive factor for recurrent pancreatic carcinoma. Samples for DNA extraction were obtained from formalin-fixed, paraffin-embedded specimens. A 0.5-microg quantity of DNA was subjected to enriched PCR and nonradioisotopic single-strand conformation polymorphism analysis. K-ras codon 12 mutations were detected in 83% (10 of 12) of invasive ductal carcinomas. In four cases, the genetic analysis of regional lymph nodal metastases and pancreatic plexus invasion of the pancreatic carcinoma yielded results concordant with those of histopathological analysis. In six cases, however, the metastases detected by genetic analysis were more advanced than was indicated by the histopathological examination. The survival rate of cases with metastases beyond the pancreaticoduodenal lymph nodes was significantly lower than that of cases with metastases limited to the pancreaticoduodenal lymph nodes or with no nodal involvement based on genetic analysis (P < 0.05). Intraoperative analysis of point mutations at K-ras codon 12 in the regional lymph nodes and the pancreatic plexus by enriched PCR/nonradioisotopic single-strand conformation polymorphism analysis is a highly accurate predictive factor for recurrent pancreatic carcinoma.
在大约90%的胰腺癌中观察到K-ras点突变。我们对胰腺浸润性导管癌区域淋巴结和神经丛微转移病例进行了基因分析,这些病例淋巴结阴性或组织病理学上转移仅限于胰十二指肠淋巴结。这些病例在我们研究所接受了根治性切除术。作为复发性胰腺癌的预测因素,在术后临床结果方面,将基因分析的效用与组织病理学研究的效用进行了比较。用于DNA提取的样本取自福尔马林固定、石蜡包埋的标本。对0.5微克的DNA进行富集PCR和非放射性单链构象多态性分析。在83%(12例中的10例)的浸润性导管癌中检测到K-ras密码子12突变。在4例中,胰腺癌区域淋巴结转移和胰腺神经丛侵犯的基因分析结果与组织病理学分析结果一致。然而,在6例中,基因分析检测到的转移比组织病理学检查显示的更严重。根据基因分析,转移超出胰十二指肠淋巴结的病例的生存率显著低于转移仅限于胰十二指肠淋巴结或无淋巴结受累的病例(P<0.05)。通过富集PCR/非放射性单链构象多态性分析对区域淋巴结和胰腺神经丛中K-ras密码子12的点突变进行术中分析是复发性胰腺癌的高度准确的预测因素。