人乳头瘤病毒与NSCLC相关性探讨

Investigation on the relevance between human papillomavirus infections and NSCLC

目的探讨人乳头瘤病毒(HPV)感染与非小细胞肺癌(NSCLC)发病相关性;分析HPV感染与NSCLC临床病理特征和多种基因突变之间的关系。方法收集NSCLC 264例原发灶和65例转移灶的石蜡包埋组织标本。选择264例原发灶邻近的上皮组织(癌旁对照组)和12例肺良性组织分别作为对照。采用免疫组化En Vision二步法检测HPV L1蛋白。选择109例NSCLC标本采用实时荧光定量PCR(RTPCR)法检测HPV16/18 L1基因序列;90例肺腺癌组织同时行EGFR、ALK、KRAS、BRAF基因状态RT-PCR法检测。结果NSCLC原发灶与转移灶HPV L1蛋白检测阳性率相近。NSCLC原发灶HPV L1蛋白阳性率显著高于癌旁对照组和肺良性对照组。不同组织类型原发灶中HPV L1蛋白检测阳性率存在明显差别,肺腺癌HPV L1蛋白检测阳性率显著高于肺鳞癌。109例NSCLC标本HPV16/18 L1基因序列11例阳性。HPV L1蛋白阳性肺腺癌患者KRAS基因突变率显著高于阴性,而EGFR、ALK、BRAF基因状态与HPV L1蛋白阳性无明显相关。结论 HPV感染与NSCLC发生可能有密切关系,尤其以肺腺癌关系更为密切;KRAS突变可能是HPV相关肺腺癌发病的驱动基因类型,为开展肺癌精准治疗指明方向。

Objective To investigate the relevance of human papillomavirus （HPV） and non small cell lung cancer （NSCLC） , and analyse the relation between the clinical pathological characteristics or a variety of genetic muta- tions of NSCLC patients and HPV infection. Methods Totally 264 cases of paraffin embedded specimens of NSCLC patients tissues were detected by immunohistochemical for HPV L1 protein, and then, 109 NSCLC specimens were chosen by RT-PCR method to detect the gene sequence of HPV16/18 L1. The adjacent epithelial tissues of primary tumor tissues and 12 cases of benign lung tissues were selected to the control group. 90 lung adenocarcino- ma（AC） specimens were tested for the genes status of EGFR,ALK,KRAS,BRAF. Results Positive rate of HPV L1 protein in NSCLC primary group was similar to that of metastases group. But the primary group positive rate was significantly higher than that in adjacent to cancer group and pulmonary benign control group. The positive rate of AC group was significantly higher than that of lung squamous cell carcinoma（SCC） group. In all 109 NSCLC carci- noma, HPV 16/18 L1 gene sequences were detected in 11 NSCLC specimens. HPV L1 protein positive patients with KRAS mutation rate was significantly higher than the HPV negative. Conclusion HPV infection may be closely related with NSCLC, especially with AC. KRAS mutations could be the driver gene type in HPV related-AC. It points out the direction of the precise treatment for lung cancer.