title: The Expression of Fibroblast Activation Protein in Clear Cell Renal Cell Carcinomas Is Associated with Synchronous Lymph Node Metastases.
abstract: Clear cell renal cell carcinoma (CCRCC) is a heterogeneous and complex disease that frequently develops distant metastases. Fibroblast activation protein (FAP) is a serine peptidase the expression of which in cancer-associated fibroblasts has been associated with higher risk of metastases and poor survival. The objective of this study was to evaluate the role of FAP in metastatic CCRCC (mCCRCC). A series of 59 mCCRCC retrospectively collected was included in the study. Metastases developed either synchronous (n = 14) or metachronous to renal disease (n = 45). Tumor specimens were obtained from both primary lesion (n = 59) and metastases (n = 54) and FAP expression was immunohistochemically analyzed. FAP expression in fibroblasts from primary tumors correlated with FAP expression in the corresponding metastatic lesions. Also, primary and metastatic FAP expression was correlated with large tumor diameter (>7cm), high grade (G3/4), high stage (pT3/4), tumor necrosis and sarcomatoid transformation. The expression of FAP in primary tumors and in their metastases was associated both with synchronous metastases and also with metastases to the lymph nodes. FAP expression in the primary tumor was correlated with worse 10-year overall survival. Immunohistochemical detection of FAP in the stromal tumor fibroblasts could be a biomarker of early lymph node metastatic status and therefore could account for the poor prognosis of FAP positive CCRCC.
authors.affiliation: Department of Physiology, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain.|Department of Nursing I, School of Nursing, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain.|Cancer Biomarkers Group, BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain.
authors.forename: Peio
authors.initials: P
authors.lastname: Errarte
authors.affiliation: Department of Pathology, Complejo Hospitalario B de Navarra, Pamplona, Navarra, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Guarch
authors.affiliation: Cancer Biomarkers Group, BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain.|Ikerbasque, Basque Foundation for Science, Bilbao, Bizkaia, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Pulido
authors.affiliation: Cancer Biomarkers Group, BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Blanco
authors.affiliation: Cancer Biomarkers Group, BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain.|Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Nunes-Xavier
authors.affiliation: Department of Physiology, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain.|Department of Nursing I, School of Nursing, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain.|Cancer Biomarkers Group, BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain.
authors.forename: Maider
authors.initials: M
authors.lastname: Beitia
authors.affiliation: Department of Physiology, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain.|Cancer Biomarkers Group, BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Gil
authors.affiliation: Department of Urology, Hospital de Getafe, Universidad Europea de Madrid, Madrid, Spain.
authors.forename: Javier C
authors.initials: JC
authors.lastname: Angulo
authors.affiliation: Cancer Biomarkers Group, BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain.|Department of Pathology, Cruces University Hospital, University of the Basque Country (UPV/EHU), Barakaldo, Bizkaia, Spain.
authors.forename: José I
authors.initials: JI
authors.lastname: López
authors.affiliation: Department of Physiology, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain.|Department of Nursing I, School of Nursing, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain.|Cancer Biomarkers Group, BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain.
authors.forename: Gorka
authors.initials: G
authors.lastname: Larrinaga
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology*; D010450:Endopeptidases; D005260:Female; D018093:Gelatinases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D012189:Retrospective Studies; D012697:Serine Endopeptidases / Q000378:metabolism*; D016019:Survival Analysis; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha