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.
Highlights
Renal cancer ranks within the top-ten list of the most frequent malignancies in Western Countries
We described the expression of this protein in a series of Clear cell renal cell carcinoma (CCRCC), and demonstrated a correlation between Fibroblast activation protein (FAP) immunostaining in cancer associated fibroblast (CAF) and poor patient outcome [13]
We have found that there is a correlation between FAP expression in the stromal fibroblasts in primary tumor and in the metastases; the negative impact of FAP on survival is mainly determined by stromal fibroblasts in the primary tumor and not in the metastases
Summary
Renal cancer ranks within the top-ten list of the most frequent malignancies in Western Countries. Clear cell renal cell carcinoma (CCRCC) is the most common histological subtype, accounting approximately for 75–80% of the cases [3]. CCRCC is frequently resistant to current chemo- and radiotherapy, and the standard treatment is complete resection of the primary tumor by radical or partial nephrectomy [4]. At the time of diagnosis approximately 25% of the patients display locally advanced or metastatic disease and about 33% of organ-confined tumors will develop metastatic disease [5]. Immunotherapy and other targeted therapies have recently provided promising results, patients with metastatic CCRCC (mCCRCC) still have a poor prognosis [6]. Biomarkers associated with metastatic status in CCRCC are important for early detection and for the identification of new therapeutic targets [6,7]
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