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Despite advances in the management of advanced clear cell renal cell carcinoma (ccRCC), robust biomarkers for prognosis and therapeutic response prediction remain elusive. Fibroblast activation protein-α (FAP), a marker of activated cancer-associated fibroblasts (CAFs), has emerged as a potential indicator of tumor aggressiveness and resistance to systemic therapies in various solid tumors. This study evaluated the clinical relevance of stromal FAP expression in a cohort of 137 patients with advanced ccRCC and long-term follow-up. FAP immunohistochemistry (IHC) was performed on primary tumor specimens and correlated with key clinicopathological features, disease-free survival (DFS), overall survival (OS), and radiological response to first-line tyrosine kinase inhibitors (TKIs). A significantly higher percentage of FAP-positive CAFs was observed in primary tumors with high histological grade, extensive local invasion (pT3–4), and advanced clinical stage (NCCN stage III–IV). Stromal FAP expression was associated with shorter DFS and OS. Moreover, tumors lacking FAP expression were more likely to achieve complete response to TKI therapy as defined by RECIST criteria. These findings highlight the potential of FAP IHC as a prognostic and predictive tool in advanced ccRCC and support further clinical validation.
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; Suárez Beatriz 2
; Solano-Iturri Jon Danel 3 ; Lecumberri, David 4
; Iturregui, Ane Miren 4
; Lawrie, Charles H 5
; Armesto María 6
; Nunes-Xavier, Caroline E 7
; Pulido, Rafael 8
; López, José I 9
; Angulo, Javier C 10
; Larrinaga Gorka 11
1 Department of Urology, Galdakao-Usansolo University Hospital, 48960 Usansolo, Spain; [email protected], Biobizkaia Health Research Institute, 48903 Barakaldo, Spain; [email protected] (J.D.S.-I.); [email protected] (C.E.N.-X.); [email protected] (R.P.); [email protected] (J.I.L.)
2 Department of Nursing, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain; [email protected]
3 Biobizkaia Health Research Institute, 48903 Barakaldo, Spain; [email protected] (J.D.S.-I.); [email protected] (C.E.N.-X.); [email protected] (R.P.); [email protected] (J.I.L.), Pathology Department, Cruces University Hospital, 48903 Barakaldo, Spain
4 Department of Urology, Cruces University Hospital, 48903 Barakaldo, Spain; [email protected] (D.L.); [email protected] (A.M.I.)
5 Molecular Oncology Group, Biogipuzkoa Health Research Institute, 20014 San Sebastián, Spain; [email protected] (C.H.L.); [email protected] (M.A.), IKERBASQUE, Basque Foundation for Science, 48009 Bilbao, Spain, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK, Sino-Swiss Institute of Advanced Technology (SSIAT), Shanghai University, Shanghai 201800, China
6 Molecular Oncology Group, Biogipuzkoa Health Research Institute, 20014 San Sebastián, Spain; [email protected] (C.H.L.); [email protected] (M.A.)
7 Biobizkaia Health Research Institute, 48903 Barakaldo, Spain; [email protected] (J.D.S.-I.); [email protected] (C.E.N.-X.); [email protected] (R.P.); [email protected] (J.I.L.), Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, 0424 Oslo, Norway
8 Biobizkaia Health Research Institute, 48903 Barakaldo, Spain; [email protected] (J.D.S.-I.); [email protected] (C.E.N.-X.); [email protected] (R.P.); [email protected] (J.I.L.), IKERBASQUE, Basque Foundation for Science, 48009 Bilbao, Spain
9 Biobizkaia Health Research Institute, 48903 Barakaldo, Spain; [email protected] (J.D.S.-I.); [email protected] (C.E.N.-X.); [email protected] (R.P.); [email protected] (J.I.L.)
10 Department of Urology, Hospital Universitario de Getafe, 28907 Getafe, Spain; [email protected], Faculty of Biomedical and Health Sciences, Department of Medicine, Universidad Europea de Madrid, 28670 Madrid, Spain
11 Biobizkaia Health Research Institute, 48903 Barakaldo, Spain; [email protected] (J.D.S.-I.); [email protected] (C.E.N.-X.); [email protected] (R.P.); [email protected] (J.I.L.), Department of Nursing, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain; [email protected], Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain