肿瘤细胞增殖（Ki-67）在肺腺癌组织学亚型中的表达及其预后意义。

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

作者信息

Li Zhihua, Li Fang, Pan Cheng, He Zhicheng, Pan Xianglong, Zhu Quan, Wu Weibing, Chen Liang

机构信息

Department of Thoracic Surgery, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.

出版信息

Lung Cancer. 2021 Apr;154:69-75. doi: 10.1016/j.lungcan.2021.02.009. Epub 2021 Feb 16.

DOI:10.1016/j.lungcan.2021.02.009

PMID:33626488

Abstract

OBJECTIVES

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.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

目的

Ki-67是指示肺癌肿瘤细胞增殖活性的关键分子标志物。然而，Ki-67在肺腺癌（LUAD）组织学亚型中的表达及其预后意义仍不清楚。

材料与方法

我们回顾性分析了2012年1月至2020年4月在我科接受手术治疗的1028例浸润性LUAD患者。评估了Ki-67表达与LUAD组织学亚型以及其他临床病理特征之间的关联。使用对数秩检验和单因素/多因素Cox比例风险回归分析进一步评估Ki-67在LUAD亚型中的预后作用。

结果

Ki-67表达在LUAD组织学亚型之间存在差异。实性为主型腺癌（SPA，46.31±24.72）的Ki-67表达水平最高，其次是微乳头型（MPA，31.71±18.14）、乳头型（PPA，22.09±19.61）、腺泡型（APA，19.73±18.71）和鳞屑为主型腺癌（LPA，9.86±8.10，P<0.001）。具有实性或微乳头成分的肿瘤的Ki-67表达也高于无实性或微乳头成分的肿瘤。此外，男性、吸烟者、肿瘤较大、有淋巴结转移和EGFR野生型与Ki-67表达升高相关。单因素分析表明，Ki-67表达增加和MPA/SPA亚型与较差的预后显著相关。值得注意的是，在多因素分析中，调整肿瘤大小和Ki-67表达后，LUAD亚型之间的生存差异消失，而Ki-67是LUAD的独立预后因素。Ki-67表达与MPA/SPA相当的MPA/SPA患者的总生存期和无病生存期不低于LPA/APA/PPA患者。