title: FGFR3 expression in primary invasive bladder cancers and matched lymph node metastases.
abstract: OBJECTIVE
  FGFR3 is considered a good therapeutic target for bladder cancer. However, to our knowledge it is unknown whether the FGFR3 status of primary tumors is a surrogate for related metastases, which must be targeted by FGFR targeted systemic therapies. We assessed FGFR3 protein expression in primary bladder tumors and matched nodal metastases.
  
  
  METHODS
  We examined matched primary tumor and nodal metastases from 150 patients with bladder cancer clinically staged as N0M0. Four samples per patient were incorporated into a tissue microarray and FGFR3 expression was assessed by immunohistochemistry. FGFR3 expression was tested for an association with categorical clinical data using the Fisher exact test, and with overall and recurrence-free survival by Kaplan-Meier analysis.
  
  
  RESULTS
  Duplicate spots from primary tumors and lymph node metastases were highly concordant (OR 8.6 and 16.7, respectively, each p <0.001). Overall FGFR protein expression levels did not differ between primary and metastatic lesions (p = 0.78). Up-regulated expression was recorded in 53 of 106 evaluable primary tumor spots and 56 matched metastases. Concordance of FGFR3 expression levels in 79 matched primary tumor and metastasis specimens was high (OR 8.45, p <0.001). In 15 and 12 patients expression was up-regulated in only metastasis and in only the primary tumor, respectively. Overall and recurrence-free survival was not related to FGFR3 expression.
  
  
  CONCLUSIONS
  FGFR3 expression in matched primary and metastasized bladder cancer specimens showed good but not absolute concordance. Thus, in most patients primary tumor FGFR3 status can guide the selection of FGFR targeted therapy.
authors.affiliation: Department of Urology, St. James's University Hospital, Leeds, United Kingdom.
authors.forename: Rafal
authors.initials: R
authors.lastname: Turo
authors.affiliation: Department of Histopathology, St. James's University Hospital, Leeds, United Kingdom.
authors.forename: Patricia
authors.initials: P
authors.lastname: Harnden
authors.affiliation: Leeds Institute of Cancer and Pathology, St. James's University Hospital, Leeds, United Kingdom.
authors.forename: Helene
authors.initials: H
authors.lastname: Thygesen
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Achim
authors.initials: A
authors.lastname: Fleischmann
authors.affiliation: Department of Urology, University of Bern, Bern, Switzerland.
authors.forename: George N
authors.initials: GN
authors.lastname: Thalmann
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland; Department of Urology, University of Bern, Bern, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Seiler
authors.affiliation: Department of Urology, St. James's University Hospital, Leeds, United Kingdom.
authors.forename: William R
authors.initials: WR
authors.lastname: Cross
authors.affiliation: Leeds Institute of Cancer and Pathology, St. James's University Hospital, Leeds, United Kingdom. Electronic address: m.a.knowles@leeds.ac.uk.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Knowles
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011446:Prospective Studies; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000096:biosynthesis*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D051498:Receptor, Fibroblast Growth Factor, Type 3
keywords: carcinoma; fibroblast growth factor; neoplasm invasiveness; neoplasm metastasis; receptor; type 3; urinary bladder