Stromal markers of activated tumor associated fibroblasts predict poor survival and are associated with necrosis in non-small cell lung cancer

Alcaraz, Jordi; Carrasco, Josep Lluís; Millares, Laura; Luis, Iuliana-Cristiana; Fernández-Porras, Francisco J.; Martínez-Romero, Anabel; Diaz-Valdivia, Natalia; Sánchez de Cos, Julio; Rami-Porta, Ramón; Seijo, Luis; Ramírez, Josep; Pajares, María José; Reguart, Noemí; Barreiro Portela, Esther; Monsó Molas, Eduard

Stromal markers of activated tumor associated fibroblasts predict poor survival and are associated with necrosis in non-small cell lung cancer

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dc.contributor.author Alcaraz, Jordi
dc.contributor.author Carrasco, Josep Lluís
dc.contributor.author Millares, Laura
dc.contributor.author Luis, Iuliana-Cristiana
dc.contributor.author Fernández-Porras, Francisco J.
dc.contributor.author Martínez-Romero, Anabel
dc.contributor.author Diaz-Valdivia, Natalia
dc.contributor.author Sánchez de Cos, Julio
dc.contributor.author Rami-Porta, Ramón
dc.contributor.author Seijo, Luis
dc.contributor.author Ramírez, Josep
dc.contributor.author Pajares, María José
dc.contributor.author Reguart, Noemí
dc.contributor.author Barreiro Portela, Esther
dc.contributor.author Monsó Molas, Eduard
dc.date.accessioned 2020-03-02T08:32:26Z
dc.date.available 2020-03-02T08:32:26Z
dc.date.issued 2019
dc.description.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.
dc.description.sponsorship This work was further supported bygrants from the Ministerio de Economía y Competitividad (MINECO/FEDER, UE) (PI13/02368 and SAF2016-79527-R to JA, FIS 12/02040to EM and FIS 12/02534 to EB), Fundació Privada Cellex (to JA),Generalitat de Catalunya AGAUR (SGR 661 to JA, SGR 801 to EM),Junta Provincial de Barcelona de l’Associació Espanyola Contra elCàncer (AECC B16-917 to JA), Fundació Catalana de Pneumologia (toEM), Sociedad Española de Neumología y Cirugía Torácica–SEPAR (PIIOncología Torácica to EM, < /GN6 > SEPAR 437 < /GN6 > to NR),and beca CONICYT (to N.D-V.)
dc.format.mimetype application/pdf
dc.identifier.citation Alcaraz J, Carrasco JL, Millares L, Luis IC, Fernández-Porras FJ, Martínez-Romero A et al. Stromal markers of activated tumor associated fibroblasts predict poor survival and are associated with necrosis in non-small cell lung cancer. Lung Cancer. 2019 Sep;135:51-160. DOI: 10.1016/j.lungcan.2019.07.020
dc.identifier.doi http://dx.doi.org/10.1016/j.lungcan.2019.07.020
dc.identifier.issn 0169-5002
dc.identifier.uri http://hdl.handle.net/10230/43756
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Lung cancer. 2019 Sep;135:51-160
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-79527-R
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.keyword Cancer associated fibroblast
dc.subject.keyword Collagen
dc.subject.keyword Lung cancer
dc.subject.keyword Necrosis
dc.subject.keyword α-SMA
dc.title Stromal markers of activated tumor associated fibroblasts predict poor survival and are associated with necrosis in non-small cell lung cancer
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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