The Expression of Fibroblast Activation Protein in Clear Cell Renal Cell Carcinomas Is Associated with Synchronous Lymph Node Metastases

PLoS One. 2016 Dec 29;11(12):e0169105. doi: 10.1371/journal.pone.0169105. eCollection 2016.

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology*
  • Endopeptidases
  • Female
  • Gelatinases / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology*
  • Lymphatic Metastasis
  • Male
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Retrospective Studies
  • Serine Endopeptidases / metabolism*
  • Survival Analysis

Substances

  • Membrane Proteins
  • Endopeptidases
  • Serine Endopeptidases
  • fibroblast activation protein alpha
  • Gelatinases

Grants and funding

This work was partially funded by Grant SAF2013-48812-R from Ministerio de Economía y Competitividad (Spain), IT 8-11/13 from de Basque Government and EHUA14/25 from de University of the Basque Country (UPV/EHU). The current work has been developed as PhD project of PE and MB, who are recipients of a Predoctoral Fellowship from the Basque Government (Exp n° PRE_2013_1_762 and PRE_2015_2_0148). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.