From the Departments of Pathology (Drs Raparia and Villa), and Pulmonary and Critical Care (Dr Raj), Northwestern University, Chicago, Illinois; and the Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas (Dr Cagle).
Arch Pathol Lab Med. 2015 Feb;139(2):189-93. doi: 10.5858/arpa.2013-0759-OA. Epub 2014 Apr 2.
Kirsten-RAS (KRAS) mutations play an important role in the carcinogenesis of a subset of lung adenocarcinomas and are associated with poorer prognosis.
To investigate the relationship of KRAS mutation status to the histologic subtype of adenocarcinoma according to the recent classification, patient demographics, tumor size, predominant histologic subtype, nodal status, and visceral pleural invasion, in an attempt to uncover the reason for the worse prognosis associated with KRAS mutation.
A total of 187 consecutive resected lung adenocarcinomas from our institution from 2008 to 2011 that were diagnosed according to the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification and screened for KRAS mutations were included in the study.
A total of 32% of the adenocarcinomas harbored the KRAS mutation. The median age in the KRAS mutation group was 69 years (range, 43-86 years), and male to female ratio was 1:2.3. The proportion of heavy smokers was significantly higher in tumors with KRAS mutation compared with wild type (83% versus 62%; P = .01). A total of 27% of tumors with KRAS mutation had pleural invasion versus 11% of tumors without KRAS mutation (P = .009). A total of 59 tumor samples were positive for KRAS mutation (25 for G12C, 14 for G12A, 8 for G12V, 7 for G12D, 3 for G12S, and 1 for G12T), and only 3 tumors harbored codon 13 mutations (G13C). Two tumors had double mutations.
KRAS mutations are more common in heavy smokers, and lung adenocarcinomas with KRAS mutation are more likely to invade the visceral pleura. Increased frequency of visceral pleural invasion may explain in part the worse prognosis associated with KRAS mutations.
KRAS 突变在一部分肺腺癌的癌变过程中起着重要作用，并且与预后较差相关。
根据最近的分类，研究 KRAS 突变状态与腺癌组织学亚型之间的关系，包括患者的人口统计学特征、肿瘤大小、主要组织学亚型、淋巴结状态和内脏胸膜侵犯，试图揭示与 KRAS 突变相关的预后较差的原因。
本研究共纳入了 187 例 2008 年至 2011 年在我院连续接受手术切除的肺腺癌患者，这些患者的诊断符合新的国际肺癌研究协会/美国胸科学会/欧洲呼吸学会分类，并进行了 KRAS 突变筛查。
腺癌中有 32%存在 KRAS 突变。KRAS 突变组的中位年龄为 69 岁（范围，43-86 岁），男女比例为 1:2.3。与 KRAS 野生型相比，KRAS 突变型肿瘤的重度吸烟者比例显著更高（83%对 62%；P =.01）。有 KRAS 突变的肿瘤中，有 27%发生了胸膜侵犯，而没有 KRAS 突变的肿瘤中，有 11%发生了胸膜侵犯（P =.009）。共有 59 个肿瘤样本 KRAS 突变阳性（25 个为 G12C，14 个为 G12A，8 个为 G12V，7 个为 G12D，3 个为 G12S，1 个为 G12T），仅有 3 个肿瘤存在 13 号密码子突变（G13C）。有 2 个肿瘤存在双突变。
KRAS 突变在重度吸烟者中更为常见，且存在 KRAS 突变的肺腺癌更有可能侵犯内脏胸膜。内脏胸膜侵犯的频率增加可能部分解释了与 KRAS 突变相关的预后较差的原因。
