EGFR and ALK Mutational Events Are Not Present in Primary Adenocarcinoma of the Urinary Bladder
Riley E Alexander, Rodolfo Montironi, Antonio Lopez-Beltran, Mingsheng Wang, Kristin M Post, Joyashree D Shen, Ashley K Arnold, Sarah A Bilbo, Shaobo Zhang, Xiaoyan "Joanne" Wang, Sean R Williamson, Michael O Koch, Noah Hahn, Gregory T MacLennan, Eva Comperat, Liang Cheng. Indiana University School of Medicine, Indianapolis, IN; Polytechnic University of the Marche Region, Ancona, Italy; Cordoba University, Cordoba, Spain; Case Western Reserve University, Cleveland, OH; Groupe Hospitalier Pitié-Salpêtrière, Paris, France
Background: Mutations in the epidermal growth factor receptor (EGFR) have been shown to play an important role in driving cancer progression in many organs. Therapies targeting the mutant EGFR have allowed for more personalized treatment options in these cancers. Much effort has been expended in identifying additional molecular alterations that will lead to targeted therapies in patients with specific EGFR mutations. Rearrangements involving ALK, most notably the EML4-ALK rearrangement, have shown considerable clinical utility in the treatment of certain lung cancers. The goal of this study was to determine whether EGFR mutations or ALK rearrangements are present in primary adenocarcinoma of the urinary bladder.
Design: 23 cases of primary bladder adenocarcinoma were identified. Clinical histories and hematoxylin and eosin (H&E) slides of each case were reviewed to confirm origination within the urinary bladder. DNA was extracted from formalin-fixed paraffin embedded tissue in all 23 cases. For EGFR analysis, PCR amplified products were analyzed on the Q24 Pyrosequencer with Qiagen EGFR Pyro® kits (Qiagen, Inc., Valencia, CA). All cases were analyzed via (FISH) using Vysis ALK Break Apart FISH Probes (Vysis, Downers Grove, IL) for detection of ALK chromosomal translocation.
Results: None of the twenty-three cases examined showed mutational events in EGFR or ALK rearrangements by FISH. Control tissues for both EGFR mutational analysis and ALK FISH exhibited the expected molecular alterations.
Conclusions: EGFR mutations and ALK rearrangements do not appear to be involved in the development of primary adenocarcinoma of the urinary bladder. Use of targeted therapies based upon these molecular alterations is unlikely to yield significant clinical benefit. Pursuit of other molecular alterations is necessary to determine the precise molecular events that lead to the development of this cancer and may provide targets for future treatment.
Category: Genitourinary (including renal tumors)
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 143, Wednesday Morning