非小细胞肺癌 KRAS G12C 突变的组织病理学谱系及相关分子变化

IF 3.6 3区 医学 Q1 PATHOLOGY
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引用次数: 0

摘要

KRAS G12C是非小细胞肺癌(NSCLC)中最常见的KRAS突变,最近已开发出针对这种突变的靶向疗法。2021 年 7 月至 2023 年 5 月期间,利物浦医院解剖病理部对 732 例 NSCLC 进行了新一代测序,我们从其中检索到 83 例(11%)连续的 KRAS G12C 突变 NSCLC 病例,并对其临床、病理和分子特征进行了分析。在 83 例 KRAS G12C 突变 NSCLC 病例中,男性 46 例(55%),女性 37 例(45%),平均年龄 72 岁。在 49 例已知临床信息的病例中,94% 的患者目前或曾经吸烟,49% 的患者在确诊时处于 IV 期,中位生存期为 12 个月。63%为组织学病例,其余为细胞学病例。82%为非黏液腺癌,传统组织学包括鳞状、针状、实变、单细胞和微乳头状,62%为分化不良。其中5例(6%)为粘液腺癌,1例为多形性癌,1例为高级别胎儿腺癌。大多数病例(89%)的 TTF1 呈阳性。KRAS G12C突变的NSCLC几乎全部发生在吸烟者身上,而且大多为非黏液腺癌,具有从分化良好到分化不良的传统组织学形态。约四分之一的患者有TP53共突变,其组织学影响和免疫特征需要在更大规模的研究中进行评估。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The histopathological spectrum and molecular changes associated with KRAS G12C mutation in non-small cell lung carcinoma

KRAS G12C is the most common KRAS mutation in non-small cell lung carcinoma (NSCLC), for which targeted therapy has recently been developed.

From the 732 cases of NSCLC that underwent next-generation sequencing at the Department of Anatomical Pathology, Liverpool Hospital, between July 2021 and May 2023, we retrieved 83 (11%) consecutive cases of KRAS G12C mutated NSCLC, and analysed their clinical, pathological, and molecular features.

Of the 83 cases of KRAS G12C mutated NSCLC, there were 46 (55%) men and 37 (45%) women, with mean age of 72 years. Of the 49 cases with known clinical information, 94% were current or ex-smokers, and 49% were stage IV at diagnosis with median survival of 12 months. Sixty-three percent were histology cases and the remainder were cytology cases. Eighty-two percent were non-mucinous adenocarcinomas, with conventional histology including lepidic, acinar, solid, single cells and micropapillary patterns, and 62% were poorly differentiated. There were five (6%) cases of mucinous adenocarcinoma, one case of pleomorphic carcinoma and one case of high-grade fetal adenocarcinoma. TTF1 was positive in the majority (89%) of cases. Nineteen (23%) cases had TP53 co-mutation, and these cases had trends towards higher PD-L1 expression, poor differentiation, and presentation as stage IV disease, but the differences were not statistically significant.

KRAS G12C mutated NSCLCs almost exclusively occurred in smokers and were mostly non-mucinous adenocarcinomas with conventional histological patterns which ranged from well to poorly differentiated. Around a quarter had TP53 co-mutation, the histological impacts and immune profile of which need to be assessed in a larger study.

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来源期刊
Pathology
Pathology 医学-病理学
CiteScore
6.50
自引率
2.20%
发文量
459
审稿时长
54 days
期刊介绍: Published by Elsevier from 2016 Pathology is the official journal of the Royal College of Pathologists of Australasia (RCPA). It is committed to publishing peer-reviewed, original articles related to the science of pathology in its broadest sense, including anatomical pathology, chemical pathology and biochemistry, cytopathology, experimental pathology, forensic pathology and morbid anatomy, genetics, haematology, immunology and immunopathology, microbiology and molecular pathology.
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