Clinicopathological characteristics and prognostic factor analysis of mucinous com-ponents heterogeneity in lung adenocarcinoma
10.13315/j.cnki.cjcep.2025.06.004
- VernacularTitle:肺腺癌黏液成分异质性的临床病理特征及预后因素分析
- Author:
Kaiwen CHI
1
;
Wei SUN
1
;
Xin YANG
1
;
Haiyue WANG
1
;
Xinying LIU
1
;
Yumeng JIANG
1
;
Xiaozheng HUANG
1
;
Dongmei LIN
1
Author Information
1. 北京大学肿瘤医院暨北京市肿瘤防治研究所病理科/恶性肿瘤发病机制及转化研究教育部重点实验室,北京 100142
- Publication Type:Journal Article
- Keywords:
lung adenocarcinoma;
invasive non-mucinous adenocarcinoma;
invasive mucinous adenocarcinoma;
mu-cins;
driver genes
- From:
Chinese Journal of Clinical and Experimental Pathology
2025;41(6):719-725
- CountryChina
- Language:Chinese
-
Abstract:
Purpose This study aimed to explore the mucinous phenotype characteristics,key points of differenti-al diagnosis and prognosis of invasive non-mucinous adenocarcinoma(INMA)and invasive mucinous adenocarcinoma(IMA)under the WHO(2021)lung adenocarcinoma classification.Methods We retrospectively collected clinico-pathological data from 522 cases of lung adenocarcinoma,including 425 INMA(66 with mucin secretion,259 without mucin secretion)and 97 IMA.Immunohistochemical(IHC)staining using the EnVision method was performed on the mucin-secreting adenocarcinoma to assess expression of TTF-1,HNF4α,MUC1,MUC4,MUC5AC,MUC5B,and MUC6.Unsupervised clustering analysis was conducted to explore phenotypic subgroups.Results 522 patients with lung adenocarcinoma ranged from 32 to 83 years old(median:61).251 cases(48.1％)were male and 271 cases(51.9％)were female.Clustering analysis divided lung adenocarcinomas into two major groups:one characterized by TTF-1-/HNF4α+and gastric-type mucins MUC5AC+/MUC6+,predominantly IMA;the other,TTF-1+/HNF4α-/MUC4+,largely INMA.A three-marker IHC panel(TTF-1,HNF4α,MUC6)distinguished IMA from mucinous IN-MA with an area under the ROC curve(AUC)of 0.957(95％CI:0.928-0.986)and a Youden's index of 0.860.Further cluster analysis of INMA cases identified four phenotypic subgroups.Prognostic analysis demonstrated that pa-tients with advanced-stage mucin-secreting INMA had significantly shorter overall survival(OS)and progression-free survival(PFS)than those without mucin secretion(5-year OS:57.1％ vs 81.8％,P=0.004;3-year PFS:40.9％ vs 62.4％,P=0.004).No significant survival differences were noted among INMA subgroups stratified by varying mucin proportions.Multivariate analysis identified pathological stage,tumor necrosis,KRAS mutation,and TTF-1 negativity as independent adverse prognostic factors for both OS and PFS in mucinous INMA.Conclusion A three-marker im-munohistochemical panel of TTF-1,HNF4α,and MUC6 is recommended to distinguish IMA from mucinous INMA.Mucus component portends a worse prognosis in advanced INMA,with necrosis,KRAS mutations,and TTF-1 negativi-ty serving as independent adverse prognostic factors in mucinous INMA.
