Stromal Markers of Activated Tumor Associated Fibroblasts Predict Poor Survival and Are Associated With Necrosis in Non-Small Cell Lung Cancer

Alcaraz J.; Carrasco, JL; Millares, L; Luis, IC; Fernandez-Porras, FJ; Martinez-romero, A; Diaz-Valdivia, N; De Cos, JS; Rami-Porta, R; Seijo, L; Ramirez, J; Pajares JM; Reguart, N; Barreiro, E; Monso, E

Keywords: survival, lung cancer, collagen, necrosis, Cancer associated fibroblast

Abstract

Objectives: Tumor associated fibroblasts (TAFs) are essential contributors of the progression of non-small cell lung cancer (NSCLC). Most lung TAFs exhibit an activated phenotype characterized by the expression of α-SMA and fibrillar collagens. However, the prognostic value of these activation markers in NSCLC remains unclear. Material and methods: We conducted a quantitative image analysis of α-SMA immunostaining and picrosirius red staining of fibrillar collagens imaged by bright-field and polarized microscopy, respectively, using tissue microarrays with samples from 220 surgical patients, which elicited a percentage of positive staining area for each marker and patient. Results: Kaplan-Meier curves showed that all TAF activation markers were significantly associated with poor survival, and their prognostic value was independent of TNM staging as revealed by multivariate analysis, which elicited an adjusted increased risk of death after 3 years of 129% and 94% for fibrillar collagens imaged with bright-field (p = 0.004) and polarized light (p = 0.003), respectively, and of 89% for α-SMA (p = 0.009). We also found a significant association between all TAF activation markers and tumor necrosis, which is often indicative of hypoxia, supporting a pathologic link between tumor desmoplasia and necrosis/hypoxia. Conclusions: Our findings identify patients with large histologic coverage of fibrillar collagens and α-SMA + TAFs to be at higher risk of recurrence and death, supporting that they could be considered for adjuvant therapy.

Más información

Título de la Revista: LUNG CANCER
Volumen: 135
Editorial: Elsevier
Fecha de publicación: 2019
Página de inicio: 151
Página final: 160
Idioma: Ingles
Notas: CiteScore: 4.52 Impact Factor: 4.599 5-Year Impact Factor: 4.443 Source Normalized Impact per Paper (SNIP): 1.276 SCImago Journal Rank (SJR): 1.905