Altered Tissue and Plasma Levels of Fibroblast Activation Protein-α (FAP) in Renal Tumours

• Main Authors: Jon Danel Solano-Iturri, Peio Errarte, María C. Etxezarraga, Enrique Echevarria, Javier Angulo, José I. López, Gorka Larrinaga
• Format: Article
• Language: English
• Published: MDPI AG 2020-11-01
• Series: Cancers
• Subjects: clear cell renal cell carcinoma; renal tumours; prognosis; FAP; cancer associated fibroblast
• Online Access: https://www.mdpi.com/2072-6694/12/11/3393

(1) Background: Renal cell carcinoma (RCC) is a heterogeneous and complex disease with only partial response to therapy, high incidence of metastasis and recurrences, and scarce reliable biomarkers indicative of progression and survival. Cancer-associated fibroblasts (CAFs) play an important role supporting and promoting renal cancer progression. (2) Methods: In this study, we analysed fibroblast activation protein-α (FAP) immunohistochemical expression and its soluble isoform (sFAP) in tumour tissues and plasma from 128 patients with renal tumours. (3) Results: FAP is expressed in the cell surface of CAFs of the tumour centre and infiltrating front from clear cell renal cell carcinomas (CCRCC, <i>n</i> = 89), papillary renal cell carcinomas (PRCC, <i>n</i> = 21), and chromophobe renal cell carcinomas (ChRCC, <i>n</i> = 8), but not in the benign tumour renal oncocytoma (RO, <i>n</i> = 10). A high expression of FAP and low levels sFAP are significantly associated with high tumour diameter, high grade, and high pT stage, lymph node invasion, development of early metastases, and worse 5-year cancer specific survival of CCRCC patients. (4) Conclusions: These findings corroborate the potential usefulness of FAP immunohistochemistry and plasma sFAP as a biomarker of CCRCC progression and point to CAF-related proteins as promising immunohistochemical biomarkers for the differential diagnosis of ChRCC and RO.