目的　探讨p53、K ras基因在肺癌患者癌组织及相应痰液中改变情况及其联合检测在肺癌早期诊断中的价值。方法　对 59例肺癌组织和 14例肺部良性组织及相应痰液 ,应用PCR SSCP 银染法检测了p53基因第 5～ 8外显子突变情况 ;应用PCR RFLP法对K ras基因突变进行了检测。结果　p53基因在肺癌组织中突变率为 37 3% ,K ras基因在肺腺癌突变率为 4 8 0 % ,其它类型肺癌突变率仅为 8 8%。相应痰液中两基因突变率分别为 33 8%和 4 4 0 % ,与组织中的突变率无明显差异 ,P <0 0 1。良性组织及相应痰液中两基因均无突变。吸烟患者的突变率 (4 8 7% ,6 8 5% )明显高于非吸烟患者的突变率 (15 0 % ,11 1% ) ,P <0 0 1;两基因的联合检测在肺癌的早期诊断中的价值 (54 2 % )明显优于单基因的检测 ,P <0 0 5。结论　痰液和组织中的基因突变率基本相似 ,即痰液中脱落细胞的分子遗传学改变能反映肺组织情况。因此以痰液为目标多基因的联合检测可能有助于肺癌的诊断。 Objective To investigate the changes of p53 and Kras genes in cancer tissues and corresponding sputum of lung cancer patients and the value of combined detection in the early diagnosis of lung cancer. Methods The mutations of exon 5-8 of p53 gene were detected in 59 lung cancer tissues and 14 benign pulmonary tissues and their corresponding sputum samples by PCR SSCP silver staining. K ras gene mutation was detected by PCR-RFLP method. . Results The mutation rate of p53 gene in lung cancer tissues was 37 3%. The mutation rate of K ras gene in lung adenocarcinoma was 48%. The mutation rate of other types of lung cancer was only 88%. The mutation rates of the two genes in the corresponding sputum were 33 8% and 44%, respectively, and there was no significant difference from the mutation rate in the tissue, P <0 01. Both genes in benign tissue and corresponding sputum were not mutated. The mutation rate in patients with smoking (48.7%, 68.5%) was significantly higher than that in non-smoking patients (15.0%, 11%), P < 0.01; the combined detection of the two genes was early in lung cancer. The value of diagnosis (54 2%) was significantly better than single gene detection, P <0 05. Conclusion The gene mutation rates in sputum and tissue are basically similar. That is, the molecular genetic changes in exfoliated cells in sputum can reflect the condition of lung tissue. Therefore, the joint detection of multiple genes targeting sputum may help diagnose lung cancer.