Family with sequence similarity 13C (FAM13C) overexpression is an independent prognostic marker in prostate cancer

// Christoph Burdelski 2, * , Laura Borcherding 1, * , Martina Kluth 1 , Claudia Hube-Magg 1 , Nathaniel Melling 1, 2 , Ronald Simon 1 , Christina Möller-Koop 1 , Philipp Weigand 1 , Sarah Minner 1 , Alexander Haese 3 , Hans Uwe Michl 3 , Maria Christina Tsourlakis 1 , Frank Jacobsen 1 , Andrea Hinsch 1 , Corinna Wittmer 1 , Patrick Lebok 1 , Stefan Steurer 1 , Jakob R. Izbicki 2 , Guido Sauter 1 , Till Krech 1 , Franziska Büscheck 1 , Till Clauditz 1 , Thorsten Schlomm 3, 4 , Waldemar Wilczak 1 1 Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 2 General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 3 Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg- Eppendorf, Hamburg, Germany 4 Department of Urology, Section for Translational Prostate Cancer Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany * These authors contributed equally to this work Correspondence to: Ronald Simon, email: R.Simon@uke.de Keywords: prostate cancer, prognosis, immunohistochemistry, FAM13C Received: June 30, 2016 Accepted: March 08, 2017 Published: March 18, 2017 ABSTRACT FAM13C, a gene with unknown function is included in several mRNA signatures for prostate cancer aggressiveness. To understand the impact of FAM13C on prognosis and its relationship to molecularly defined subsets, we analyzed FAM13C expression by immunohistochemistry on a tissue microarray containing 12,400 prostate cancer specimens. Results were compared to phenotype, ERG status, genomic deletions of 3p, 5q, 6q and PTEN , and biochemical recurrence. FAM13C was detectable in cell nuclei of cancerous and non-neoplastic prostate cells. 67.5% of 9,633 interpretable cancers showed FAM13C expression: strong in 28.3%, moderate in 24.6% and weak in 14.6%. Strong FAM13C expression was linked to advanced pT stage, high Gleason grade, positive lymph node status, and early biochemical recurrence ( p < 0.0001 each). FAM13C expression was associated with TMPRSS2:ERG fusions. It was present in 85% of ERG positive but in only 54% of ERG negative cancers ( p < 0.0001), and in 91.1% of PTEN deleted but in only 69.2% of PTEN non-deleted cancers ( p < 0.0001). The prognostic role of FAM13C expression was independent of classical and quantitative Gleason grade, pT stage, pN stage, surgical margin status and preoperative PSA. In conclusion, the results of our study demonstrate that expression of FAM13C is an independent prognostic marker in prostate cancer. Finding FAM13C also in non-neoplastic prostate tissues highlights the importance of properly selecting cancer-rich areas for RNA-based FAM13C expression analysis.