KRAS Mutation Is Present in a Small Subset of Primary Urinary Bladder Adenocarcinomas
Riley E Alexander, Antonio Lopez-Beltran, Rodolfo Montironi, Gregory T MacLennan, GuoRong R Chen, Kristin M Post, Sarah A Bilbo, Joy D Sen, Kari Meehan, Anita Cornwell, Liang Cheng. Indiana University School of Medicine, Indianapolis, IN; Cordoba University, Cordoba, Spain; Polytechnic University of the Marche Region (Ancona), United Hospitals, Ancona, Italy; Case Western Reserve University, Cleveland, OH; First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China
Background: The realization that the presence of KRAS mutations is a near absolute contraindication to the use of EGFR-targeted therapies in colonic adenocarcinoma and non-small cell lung carcinoma has significantly altered the clinical management of individual patients with these types of cancer. The aim of this study is to determine whether KRAS mutations occur in primary bladder adenocarcinoma and/or urothelial carcinoma with glandular differentiation.
Design: Twenty cases of primary bladder adenocarcinoma were identified. Clinical histories and hematoxylin and eosin slides of each case were reviewed to confirm primary bladder origin. An additional 5 cases of urothelial carcinoma with significant degree of glandular differentiation were included. DNA was extracted from formalin-fixed paraffin embedded tissue, amplified with Shifted Assay Termination (STA) technology. The STA reaction recognizes wild type or mutant target sequences and selectively extends detection primers with 1 to 20 labeled nucleotides. This extension is repeated 20 times to enrich the mutation signal. The enriched mutation signals are then detected by capillary electrophoresis fragment analysis. The PCR amplification products were analyzed on an ABI-3130XL analyzer with GeneMapper® software (Applied Biosystems® Inc., Foster City, CA). Analysis included 6 different mutations on codon 12 (G12C, G12V, G12S, G12D, G12R, G12A) and codon 13 (G13C, G13V, G13S, G13D, G13R, G13A) along with negative and positive controls. 55 cases of colonic adenocarcinomas were also analyzed.
Results: Two of twenty (10%) cases of primary urinary bladder adenocarcinoma were found to contain a KRAS mutation. Both cases exhibited G13D mutations on codon 13. None of the 5 cases of urothelial carcinoma with glandular differentiation displayed KRAS mutation. Eighteen (33%) of 55 cases of colonic adenocarcinoma contained a KRAS mutation.
Conclusions: KRAS mutations are present in a small subset of primary urinary bladder adenocarcinomas, suggesting a possible role in tumorigenesis. KRAS mutations do not provide a means of distinguishing between primary urinary bladder adenocarcinoma and primary colonic adenocarcinoma.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 141, Monday Morning