title: EGFR alterations and EML4-ALK rearrangement in primary adenocarcinoma of the urinary bladder.
abstract: The identification of mutations in epidermal growth factor receptor (EGFR) and translocations involving anaplastic lymphoma kinase (ALK) in lung adenocarcinoma has drastically changed understanding of the disease and led to the development of targeted therapies. Adenocarcinoma of the urinary bladder is rare and poorly understood at the molecular level. We undertook this study to determine whether EGFR mutations, increases in EGFR copy number, or ALK translocations are present in these tumors. Twenty-eight cases of primary bladder adenocarcinoma were analyzed. For EGFR mutational analysis, PCR-amplified products were analyzed on the Q24 Pyrosequencer with Qiagen EGFR Pyro Kits. All cases were analyzed via fluorescence in situ hybridization (FISH) using Vysis ALK Break Apart FISH Probes for detection of ALK chromosomal translocation and Vysis Dual Color Probes to assess for increased gene copy number of EGFR. None of the 28 cases examined showed mutational events in EGFR or ALK rearrangements. EGFR polysomy was seen in 10 out of 28 (36%) cases. No correlation with EGFR polysomy was seen in the tumors with respect to age, histologic subtypes, pathologic stage, or lymph node metastasis. In summary, EGFR mutations and ALK rearrangements do not appear to be involved in the development of primary adenocarcinoma of the urinary bladder. A subgroup of cases (36%), however, demonstrated increased gene copy number of EGFR by FISH.
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Riley E
authors.initials: RE
authors.lastname: Alexander
authors.affiliation: Institute of Pathological Anatomy and Histopathology, School of Medicine, Polytechnic University of the Marche Region (Ancona), United Hospitals, Ancona, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.affiliation: Department of Pathology, Cordoba University, Cordoba, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Beltran
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Sean R
authors.initials: SR
authors.lastname: Williamson
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Post
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Joyashree D
authors.initials: JD
authors.lastname: Sen
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Ashley K
authors.initials: AK
authors.lastname: Arnold
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Koch
authors.affiliation: Department of Internal Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Noah M
authors.initials: NM
authors.lastname: Hahn
authors.affiliation: Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Masterson
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: MacLennan
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Darrell D
authors.initials: DD
authors.lastname: Davidson
authors.affiliation: Department of Pathology, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Eva
authors.initials: E
authors.lastname: Compérat
authors.affiliation: 1] Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA [2] Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D018628:Gene Dosage; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
chemical_list: C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion; C512478:EGFR protein, human; D066246:ErbB Receptors