title: Fibroblast activation protein predicts prognosis in clear cell renal cell carcinoma.
abstract: Clear cell renal cell carcinoma is a complex disease with only partial response to therapy and scarce reliable clinical parameters indicative of progression and survival. Fibroblast activation protein expression has been correlated with prognosis in several malignancies but never in renal cancer. We aim to analyze the immunohistochemical expression of fibroblast activation protein in 208 clear cell renal cell carcinomas and to evaluate its impact on the prognosis and survival. A positive cytoplasmic immunostaining of this protein in the stromal fibroblasts associated to cancer cells is associated with large tumor diameter (≥4cm), high-grade (G3/4) tumors, and high-stage (≥pT3) tumors. Fibroblast activation protein-positive cases had significantly shorter survivals after 5 (P=.00015), 10 (P=.0000042), and 15 (P=.000043) years of follow-up, with a hazard ratio of 0.31. Multivariate analysis showed that fibroblast activation protein (P=.00117) was stronger than grade and stage in predicting clinical aggressiveness in clear cell renal cell carcinoma. This study confirms the usefulness of fibroblast activation protein detection in the stromal fibroblast associated to cancer in clear cell renal cell carcinoma and adds a new immunohistochemical marker to predict clinical behavior in these patients.
authors.affiliation: Department of Pathology, Cruces University Hospital, University of the Basque Country (UPV/EHU), Barakaldo 48903, Bizkaia, Spain; Cancer Biomarkers Group, BioCruces Health Research Institute, Barakaldo 48903, Bizkaia, Spain. Electronic address: joseignacio.lopez@osakidetza.eus.
authors.forename: José I
authors.initials: JI
authors.lastname: López
authors.affiliation: Cancer Biomarkers Group, BioCruces Health Research Institute, Barakaldo 48903, Bizkaia, Spain; Department of Physiology, University of the Basque Country (UPV/EHU), Leioa 48940, Bizkaia, Spain.
authors.forename: Peio
authors.initials: P
authors.lastname: Errarte
authors.affiliation: Quantitative Biomedicine Unit, BioCruces Health Research Institute, Barakaldo 48903, Bizkaia, Spain.
authors.forename: Asier
authors.initials: A
authors.lastname: Erramuzpe
authors.affiliation: Department of Pathology, Complejo Hospitalario B de Navarra, Pamplona 31008, Navarra, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Guarch
authors.affiliation: Quantitative Biomedicine Unit, BioCruces Health Research Institute, Barakaldo 48903, Bizkaia, Spain; Ikerbasque, Basque Foundation for Science, Bilbao 48011, Bizkaia, Spain; Department of Cell Biology and Histology, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Cortés
authors.affiliation: Department of Urology, Hospital de Getafe, Universidad Europea de Madrid, Getafe, 28907, Madrid, Spain.
authors.forename: Javier C
authors.initials: JC
authors.lastname: Angulo
authors.affiliation: Cancer Biomarkers Group, BioCruces Health Research Institute, Barakaldo 48903, Bizkaia, Spain; Ikerbasque, Basque Foundation for Science, Bilbao 48011, Bizkaia, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Pulido
authors.affiliation: Cancer Biomarkers Group, BioCruces Health Research Institute, Barakaldo 48903, Bizkaia, Spain; Department of Physiology, University of the Basque Country (UPV/EHU), Leioa 48940, Bizkaia, Spain.
authors.forename: Jon
authors.initials: J
authors.lastname: Irazusta
authors.affiliation: Department of Urology, Cruces University Hospital, University of the Basque Country (UPV/EHU), Barakaldo 48903, Bizkaia, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Llarena
authors.affiliation: Cancer Biomarkers Group, BioCruces Health Research Institute, Barakaldo 48903, Bizkaia, Spain; Department of Physiology, University of the Basque Country (UPV/EHU), Leioa 48940, Bizkaia, Spain; Department of Nursing I, School of Nursing, University of the Basque Country (UPV/EHU), Leioa 48940, Bizkaia, Spain.
authors.forename: Gorka
authors.initials: G
authors.lastname: Larrinaga
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D000072645:Cancer-Associated Fibroblasts / Q000737:chemistry* / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D010450:Endopeptidases; D005260:Female; D018093:Gelatinases / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000032:analysis*; D013030:Spain; D017154:Stromal Cells / Q000737:chemistry* / Q000473:pathology; D013997:Time Factors; D047368:Tumor Burden; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D014408:Biomarkers, Tumor; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha
keywords: Clear cell renal cell carcinoma; Fibroblast activation protein; Immunohistochemistry; Prognosis; Survival