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.