Dept of Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway.
Dept of Pathology, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway.
Lung Cancer. 2017 Jan;103:52-57. doi: 10.1016/j.lungcan.2016.11.018. Epub 2016 Nov 28.
Mutation in the PIK3CA gene is reported frequent in squamous cell carcinomas of the lung, but its potential prognostic role is still obscure. We have studied the prognostic importance of PIK3CA mutations as well as the relation to other markers in a large number of early stage lung cancers of squamous carcinoma subtype.
Tumour tissue was obtained from 308 consecutively operated lung cancer patients with squamous cell carcinoma in the period 2003-2013. DNA was isolated according to standard procedures, and mutation analysis was done with either the SnapShot method and/or using PIK3CA specific primers in the Cobas system. PD-L1-expression was analysed with immunohistochemistry After thorough follow-up (median 67.6 months), overall survival and time to relapse was calculated.
Tumour tissue from 102 females and 206 males were analysed. 167 (54.2%) were in stage I, 96 (31.2%) in stage II and 45 (14.6%) in stage III. PIK3CA mutation was found in 35 (11.4%) patients, most frequently in exon 20. There were no differences in sex, stage or smoking behaviour between mutated and non-mutated cases. Patients with PIK3CA mutations had a significantly longer overall survival (p=0.042) and time to relapse (p=0.030) than non-mutated cases, and the difference in time to relapse was also retained in stage I-cases (p=0.044). PD-L1-expression was less frequent among mutated cases.
Our results indicate that PIK3CA mutations may confer a survival advantage in early stage squamous cell lung cancers, but further work is needed to confirm this finding.
PIK3CA 基因突变在肺鳞癌中报道较为频繁,但其潜在的预后作用尚不清楚。我们研究了 PIK3CA 突变在大量早期肺鳞癌患者中的预后意义以及与其他标志物的关系。
我们从 2003 年至 2013 年连续手术治疗的 308 例肺鳞癌患者的肿瘤组织中获得了肿瘤组织。按照标准程序分离 DNA,并使用 SnapShot 方法或 Cobas 系统中的 PIK3CA 特异性引物进行突变分析。采用免疫组织化学法分析 PD-L1 表达。在彻底随访(中位随访时间 67.6 个月)后,计算总生存期和复发时间。
共分析了 102 名女性和 206 名男性患者的肿瘤组织。167 例(54.2%)为 I 期,96 例(31.2%)为 II 期,45 例(14.6%)为 III 期。35 例(11.4%)患者存在 PIK3CA 突变,最常见于外显子 20。突变和非突变病例在性别、分期或吸烟行为方面无差异。与非突变病例相比,PIK3CA 突变患者的总生存期(p=0.042)和复发时间(p=0.030)显著延长,且在 I 期病例中,复发时间的差异仍然存在(p=0.044)。突变病例中 PD-L1 表达频率较低。
我们的结果表明,PIK3CA 突变可能为早期肺鳞癌患者提供生存优势,但需要进一步研究来证实这一发现。