Abstract
Simple SummaryMalignant epithelial tumour’s behaviour in the kidney has traditionally been analysed attending to different prognostic parameters focussed on the proliferating neoplastic cell. This is the case of renal cell carcinoma (RCC), in which a large tumour diameter, high histological grade, and the presence of necrosis, among other factors, have been related with a high risk of distant metastasis and, therefore, worse survival. Recently, several elements of the tumour microenviroment, such as cancer-associated fibroblasts (CAFs), are being studied in order to develop more accurate diagnostic and therapeutic approaches. We present data that support that the fibroblast activation protein-α (FAP), a CAF biomarker, provides interesting information both in tumour tissues and in plasma from patients with RCC. (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, n = 89), papillary renal cell carcinomas (PRCC, n = 21), and chromophobe renal cell carcinomas (ChRCC, n = 8), but not in the benign tumour renal oncocytoma (RO, n = 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.
Highlights
Renal cell carcinoma (RCC) is the third most common genitourinary cancer and ranks within the top-ten list of the most frequent malignancies in Western countries [1,2]
It is a classic observation that patients with Clear cell renal cell carcinoma (CCRCC) had a poorer prognosis compared with patients with papillary renal cell carcinoma (PRCC) and chromophobe renal cell carcinoma (ChRCC) [3]
The non-parametric Rho Spearman test was performed to assess if fibroblast activation protein-α (FAP) protein expression and plasma levels vary according to the gender or age of the patients
Summary
Renal cell carcinoma (RCC) is the third most common genitourinary cancer and ranks within the top-ten list of the most frequent malignancies in Western countries [1,2]. Clear cell renal cell carcinoma (CCRCC) is the most common histological subtype (75–80%) and, together with papillary renal cell carcinoma (PRCC) (10–15%), it arises from the proximal tubule of the nephron [1,2]. The chromophobe renal cell carcinoma (ChRCC) (5% of cases) and the renal oncocytoma (RO) (5%), which is a benign tumour, are originated in the intercalated cells of the distal nephron and share a common histogenetic lineage [3]. Defined variants follow different genetic drivers, variable therapeutic response to anti-angiogenic therapies, and pursue a different clinical evolution [5]. Systemic treatments (tyrosine kinase and immune checkpoint inhibitors) for patients with metastatic non-clear cell RCC tend to be significantly less effective than for CCRCC, and optimal therapy for non-clear cell RCC remains unclear and warrants further study [6]
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