Tumor cell proliferation (Ki-67) expression and its prognostic significance in histological subtypes of lung adenocarcinoma

• Published in: Lung cancer (Amsterdam, Netherlands) Vol. 154; pp. 69 - 75
• Main Authors: Li, Zhihua, Li, Fang, Pan, Cheng, He, Zhicheng, Pan, Xianglong, Zhu, Quan, Wu, Weibing, Chen, Liang
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.04.2021
• Subjects: EGFR mutations; Histological subtypes; Ki-67; Lung adenocarcinoma; Survival analysis; PPA; Ki-67; LN; EGFR mutations; OS; SPA; Lung adenocarcinoma; IHC: IQR; LUAD; Histological subtypes; DFS; Survival analysis; APA; LPA; MPA
• ISSN: 0169-5002; 1872-8332; 1872-8332
• DOI: 10.1016/j.lungcan.2021.02.009

•The SPA subtype had the highest level of Ki-67, followed by MPA, PPA, APA and LPA.•Males, smoking, tumor size, LN + and EGFR wild type correlated with Ki-67 level.•Patients with a higher Ki-67 expression level had a poorer OS and DFS.•MPA/SPA had non-inferior prognosis than LPA/APA/PPA with a comparable Ki-67 level.•Ki-67 and tumor size might contribute to the survival difference between subtypes. Ki-67 is a key molecular marker to indicate the proliferative activity of tumor cells in lung cancer. However, Ki-67 expression and its prognostic significance in histological subtypes of lung adenocarcinoma (LUAD) remain unclear. We retrospectively analyzed 1028 invasive LUAD patients who underwent surgery treatment between January 2012 and April 2020 in our department. Associations between Ki-67 expression and histological subtypes of LUAD, as well as other clinicopathological characteristics, were evaluated. The prognostic role of Ki-67 in LUAD subtypes was further assessed using log-rank test and univariate/multivariate Cox proportional hazards regression analyses. Ki-67 expression differed across LUAD histological subtypes. The solid-predominant adenocarcinoma (SPA, 46.31 ± 24.72) had the highest expression level of Ki-67, followed by micropapillary (MPA, 31.71 ± 18.14), papillary (PPA, 22.09 ± 19.61), acinar (APA, 19.73 ± 18.71) and lepidic-predominant adenocarcinoma (LPA, 9.86 ± 8.10, P <  0.001). Tumors with solid or micropapillary components also had a higher Ki-67 expression than those without solid or micropapillary components. Besides, males, smokers, larger tumor size, lymph node metastasis and EGFR wild type were correlated with elevated Ki-67 expression. Univariate analysis indicated that increased Ki-67 expression and MPA/SPA subtypes were significantly associated with a poorer prognosis. Notably, the survival differences between LUAD subtypes vanished after adjusting for tumor size and Ki-67 expression in multivariate analysis, while Ki-67 was an independent prognostic factor of LUAD. Patients with MPA/SPA had non-inferior overall and disease-free survival than LPA/APA/PPA patients with a Ki-67 expression comparable to MPA/SPA subjects. Ki-67 expression varied considerably according to the predominant histological subtypes of LUAD. Ki-67 expression level and tumor size contributed to the survival differences between LUAD histological subtypes.