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基于国际肺癌研究协会组织学分级和免疫评分的 KRAS 突变型浸润性非黏液腺癌预后分类。

A prognostic classification based on the International Association for the Study of Lung Cancer histologic grading and immunoscore in KRAS-mutant invasive non-mucinous adenocarcinoma.

机构信息

Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.

Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer; Key Laboratory of Cancer Prevention and Therapy; Clinical Research, Tianjin, China.

出版信息

Thorac Cancer. 2022 Apr;13(7):1050-1058. doi: 10.1111/1759-7714.14360. Epub 2022 Mar 4.

Abstract

BACKGROUND

Tumor immune cell infiltration is important in the prognosis of patients with lung adenocarcinoma. The aim of this study was to develop a prognostic classification based on the tumor immunoscore.

METHODS

Patients with KRAS-mutant invasive non-mucinous lung adenocarcinoma who underwent radical surgery were enrolled in the study. Histologic grading was assessed according to the recommendations of the International Association for the Study of Lung Cancer. Programmed death-ligand 1 (PD-L1) and CD8 expression was detected using immunohistochemistry. The number of CD8 tumor-infiltrating lymphocytes (TILs) per high-power field was assessed. A classification based on histological grade and CD8 TIL level was established (Grading-Immunoscore type): low-to-medium grade with high or low infiltration (type A); high-grade, high-infiltration (type B); and high-grade, low-infiltration (type C).

RESULTS

A total of 112 patients participated. In the multivariable analysis, histological grading and level of CD8 TILs were independent prognostic factors for overall survival (OS) and progression-free survival (PFS) (p < 0.001 and p = 0.007, respectively). Patients with type A tumors had the best OS and PFS, whereas those with type C tumors had the worst OS (89.6%, 65.0%, and 29.5% 5-year OS for types A, B, and C, respectively). PD-L1 positivity and high expression rate was highest in type B tumors (tumor proportion score [TPS] ≥ 1%: 29.4%, 73.1%, and 42.9%; TPS ≥50%: 7.8%, 42.3%, and 17.1%, for types A, B, and C, respectively).

CONCLUSIONS

The Grading-Immunoscore classification refines the prognostic grouping of histological grading and might aid in the screening of potential candidates for immunotherapy in patients with KRAS-mutant adenocarcinoma.

摘要

背景

肿瘤免疫细胞浸润对肺腺癌患者的预后很重要。本研究旨在建立一种基于肿瘤免疫评分的预后分类方法。

方法

本研究纳入了接受根治性手术治疗的 KRAS 突变型浸润性非黏液性肺腺癌患者。组织学分级按照国际肺癌研究协会的建议进行评估。使用免疫组织化学检测程序性死亡配体 1(PD-L1)和 CD8 的表达。评估每高倍镜视野下的 CD8 肿瘤浸润淋巴细胞(TIL)数量。根据组织学分级和 CD8 TIL 水平建立分类(分级-免疫评分类型):高低分级伴有高或低浸润(A 型);高级别、高浸润(B 型);高级别、低浸润(C 型)。

结果

共有 112 名患者参与。多变量分析显示,组织学分级和 CD8 TIL 水平是总生存(OS)和无进展生存(PFS)的独立预后因素(p<0.001 和 p=0.007)。A 型肿瘤患者的 OS 和 PFS 最佳,而 C 型肿瘤患者的 OS 最差(A、B 和 C 型患者的 5 年 OS 分别为 89.6%、65.0%和 29.5%)。B 型肿瘤的 PD-L1 阳性率和高表达率最高(肿瘤比例评分[TPS]≥1%:29.4%、73.1%和 42.9%;TPS≥50%:7.8%、42.3%和 17.1%,分别为 A、B 和 C 型)。

结论

分级-免疫评分分类方法细化了组织学分级的预后分组,可能有助于筛选 KRAS 突变型腺癌患者免疫治疗的潜在候选人群。

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