FGFR3 expression in primary and metastatic urothelial carcinoma of the bladder

Cancer Medicine

Elizabeth A. Guancial¹  Lillian Werner²  Joaquim Bellmunt¹  Aristotle Bamias⁴  Toni K. Choueiri¹  Robert Ross¹  Fabio A. Schutz¹  Rachel S. Park¹  Robert J. O'Brien¹  Michelle S. Hirsch⁵  Justine A. Barletta⁵  David M. Berman³  Rosina Lis⁶  Massimo Loda⁶  Edward C. Stack⁶  Levi A. Garraway¹  Markus Riester²  Franziska Michor²  Philip W. Kantoff¹ 

[1] Dana-Farber Cancer Institute, Boston, Massachusetts;Biostatistics and Computational Biology, Harvard Medical School, Boston, Massachusetts;Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada;Department of Clinical Therapeutics, University of Athens Medical School, Athens, Greece;Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;Center for Molecular Oncologic Pathology, Brigham and Women's Hospital, Boston, Massachusetts

关键词: Biomarker;    bladder cancer;    FGFR3;    metastatic urothelial carcinoma;    muscle‐invasive urothelial carcinoma;    targeted therapy;   

DOI  :  10.1002/cam4.262

来源: Wiley

【 摘 要 】

Abstract

While fibroblast growth factor receptor 3 (FGFR3) is frequently mutated or overexpressed in nonmuscle-invasive urothelial carcinoma (UC), the prevalence of FGFR3 protein expression and mutation remains unknown in muscle-invasive disease. FGFR3 protein and mRNA expression, mutational status, and copy number variation were retrospectively analyzed in 231 patients with formalin-fixed paraffin-embedded primary UCs, 33 metastases, and 14 paired primary and metastatic tumors using the following methods: immunohistochemistry, NanoString nCounterTM, OncoMap or Affymetrix OncoScanTM array, and Gain and Loss of Analysis of DNA and Genomic Identification of Significant Targets in Cancer software. FGFR3 immunohistochemistry staining was present in 29% of primary UCs and 49% of metastases and did not impact overall survival (P = 0.89, primary tumors; P = 0.78, metastases). FGFR3 mutations were observed in 2% of primary tumors and 9% of metastases. Mutant tumors expressed higher levels of FGFR3 mRNA than wild-type tumors (P < 0.001). FGFR3 copy number gain and loss were rare events in primary and metastatic tumors (0.8% each; 3.0% and 12.3%, respectively). FGFR3 immunohistochemistry staining is present in one third of primary muscle-invasive UCs and half of metastases, while FGFR3 mutations and copy number changes are relatively uncommon.

【 授权许可】

CC BY   
© 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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