Silini E M, Bosi F, Pellegata N S, Volpato G, Romano A, Nazari S, Tinelli C, Ranzani G N, Solcia E, Fiocca R
Department of Human Pathology, University of Pavia, Italy.
Virchows Arch. 1994;424(4):367-73. doi: 10.1007/BF00190558.
Activation of K-ras gene by point mutations, a common finding in lung adenocarcinomas, has been suggested to decrease patient survival. We investigated 109 lung adenocarcinomas, mostly small, peripheral, stage I tumours (81/109) for presence of K-ras gene mutations at codons 12 and 13. Mutations were detected by denaturing gradient gel electrophoresis analysis of specific sequences amplified by polymerase chain reaction from DNA extracted from archival pathological material. Thirty-three of 109 (30.3%) tumours showed mutations at codon 12 (28/33, 84.8%) or 13 (5/33, 15.2%) of the gene. Mutations and type of nucleotide substitutions were differently distributed among cytological subtypes, being more prevalent among less differentiated (G2 and G3) tumours and among bronchial than bronchiolo-alveolar type adenocarcinomas. Survival analysis showed an adverse effect of K-ras mutation on survival, restricted to stage I tumours. Median survival for 81 stage I patients was 30 months for non-mutated tumours versus 20 months for mutated tumours (p = 0.016). Multivariate analysis showed that age of patient (p = 0.001) and K-ras mutation status (p = 0.04) were the only independent factors influencing survival significantly. These data strengthen the hypothesis that K-ras gene mutations may be useful in identifying a subgroup of patients with poor outcome.
K-ras基因点突变激活在肺腺癌中很常见，有研究表明这会降低患者生存率。我们对109例肺腺癌进行了研究，其中大部分是小型、外周型、I期肿瘤（81/109），检测其第12和13密码子处K-ras基因突变情况。通过聚合酶链反应从存档病理材料提取的DNA中扩增特定序列，再经变性梯度凝胶电泳分析来检测突变。109例肿瘤中有33例（30.3%）在该基因的第12密码子（28/33，84.8%）或第13密码子（5/33，15.2%）处出现突变。突变和核苷酸替换类型在细胞亚型中的分布不同，在低分化（G2和G3）肿瘤以及支气管型腺癌中比细支气管肺泡型腺癌更常见。生存分析显示K-ras突变对生存有不良影响，且仅限于I期肿瘤。81例I期患者中，未突变肿瘤的中位生存期为30个月，而突变肿瘤为20个月（p = 0.016）。多变量分析表明，患者年龄（p = 0.001）和K-ras突变状态（p = 0.04）是仅有的显著影响生存的独立因素。这些数据强化了K-ras基因突变可能有助于识别预后不良患者亚组的假设。
