Stromal FAP is an independent poor prognosis marker in non-small cell lung adenocarcinoma and associated with p53 mutation

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2021-05, Vol.155, p.10-19
• Main Authors: Moreno-Ruiz, Pablo, Corvigno, Sara, te Grootenhuis, Nienke C., La Fleur, Linnéa, Backman, Max, Strell, Carina, Mezheyeuski, Artur, Hoelzlwimmer, Gabriele, Klein, Christian, Botling, Johan, Micke, Patrick, Östman, Arne
• Format: Article
• Language: English
• Subjects: Adenocarcinoma of Lung - diagnosis; Adenocarcinoma of Lung - genetics; Aged; Biomarkers; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - genetics; CD8; Endopeptidases - genetics; FAP; Female; Fibroblast; Humans; Lung Neoplasms - diagnosis; Lung Neoplasms - genetics; Medicin och hälsovetenskap; Membrane Proteins - genetics; Mutation; Non-small-cell lung cancer; Pathology; Patologi; PDGFβR; Prognosis; Stroma; Tumor Suppressor Protein p53 - genetics; α-SMA
• ISSN: 0169-5002; 1872-8332; 1872-8332
• DOI: 10.1016/j.lungcan.2021.02.028

•High FAP stroma intensity is a poor prognosis marker in non-small cell lung cancer.•P53 mutation is positively associated with fibroblast stroma features.•Fibroblast markers show subset-specific associations with CD8 cells. Fibroblasts regulate tumor growth and immune surveillance. Here, we study FAP, PDGFβR and α-SMA fibroblast markers in a well-annotated clinical cohort of non–small-cell lung cancer (NSCLC) for analyses of associations with immune cell infiltration, mutation status and survival. A well-annotated NSCLC cohort was subjected to IHC analyses of stromal expression of FAP, PDGFβR and α-SMA and of stromal CD8 density. Fibroblast markers-related measurements were analyzed with regard to potential associations with CD8 density, cancer genetic driver mutations, survival and PD-L1 expression in the whole NSCLC cohort and in subsets of patients. High stromal FAP expression was identified as an independent poor prognostic marker in the whole study population (HR 1.481; 95 % CI, 1.012–2.167, p = 0.023) and in the histological subset of adenocarcinoma (HR 1.720; 95 % CI, 1.126–2.627, p = 0.012). Among patients with adenocarcinoma, a particularly strong association of FAP with poor survival was detected in patients with low stromal CD8 infiltration, and in other subpopulations identified by specific clinical characteristics; elderly patients, females, non-smokers and patients with normal ECOG performance status. α-SMA expression was negatively associated with CD8 infiltration in non-smokers, but none of the fibroblast markers expression was associated with CD8 density in the whole study population. Significant associations were detected between presence of p53 mutations and high α-SMA (p = 0.003) and FAP expression (p