Alcaraz J, Carrasco JL, Millares L, et al. - Given the exhibition of an activated phenotype characterized by the expression of α-SMA and fibrillar collagens in most lung tumor-associated fibroblasts (TAFs), which are essential contributors of the progression of non-small cell lung cancer (NSCLC), researchers investigated these activation markers in NSCLC for their prognostic value. A quantitative image analysis of α-SMA immunostaining and picrosirius red staining of fibrillar collagens imaged by bright-field and polarized microscopy, respectively, was performed using tissue microarrays with samples from 220 surgical patients, which elicited a percentage of positive staining area for each marker and patient. As per Kaplan-Meier curves, there is a significant association of all TAF activation markers with poor survival, and as per multivariate analysis, their prognostic value was independent of TNM staging. All TAF activation markers were identified to be significantly associated with tumor necrosis, which is often indicative of hypoxia. This supports a pathologic link between tumor desmoplasia and necrosis/hypoxia. Findings thereby suggest a higher risk of recurrence and death for patients with large histologic coverage of fibrillar collagens and α-SMA + TAFs. This support considering adjuvant therapy for these patients.