PMID- 23887300 OWN - NLM STAT- MEDLINE DCOM- 20140929 LR - 20230210 IS - 1530-0285 (Electronic) IS - 0893-3952 (Linking) VI - 27 IP - 1 DP - 2014 Jan TI - EGFR alterations and EML4-ALK rearrangement in primary adenocarcinoma of the urinary bladder. PG - 107-12 LID - 10.1038/modpathol.2013.132 [doi] AB - 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. FAU - Alexander, Riley E AU - Alexander RE AD - Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. FAU - Montironi, Rodolfo AU - Montironi R AD - Institute of Pathological Anatomy and Histopathology, School of Medicine, Polytechnic University of the Marche Region (Ancona), United Hospitals, Ancona, Italy. FAU - Lopez-Beltran, Antonio AU - Lopez-Beltran A AD - Department of Pathology, Cordoba University, Cordoba, Spain. FAU - Williamson, Sean R AU - Williamson SR AD - Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. FAU - Wang, Mingsheng AU - Wang M AD - Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. FAU - Post, Kristin M AU - Post KM AD - Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. FAU - Sen, Joyashree D AU - Sen JD AD - Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. FAU - Arnold, Ashley K AU - Arnold AK AD - Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. FAU - Zhang, Shaobo AU - Zhang S AD - Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. FAU - Wang, Xiaoyan AU - Wang X AD - Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. FAU - Koch, Michael O AU - Koch MO AD - Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA. FAU - Hahn, Noah M AU - Hahn NM AD - Department of Internal Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. FAU - Masterson, Timothy A AU - Masterson TA AD - Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA. FAU - MacLennan, Gregory T AU - MacLennan GT AD - Department of Pathology, Case Western Reserve University, Cleveland, OH, USA. FAU - Davidson, Darrell D AU - Davidson DD AD - Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. FAU - Comperat, Eva AU - Comperat E AD - Department of Pathology, Groupe Hospitalier Pitie-Salpetriere, Paris, France. FAU - Cheng, Liang AU - Cheng L AD - 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. LA - eng PT - Journal Article DEP - 20130726 PL - United States TA - Mod Pathol JT - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JID - 8806605 RN - 0 (EML4-ALK fusion protein, human) RN - 0 (Oncogene Proteins, Fusion) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Adenocarcinoma/enzymology/*genetics/pathology MH - DNA Mutational Analysis MH - ErbB Receptors/*genetics MH - Gene Dosage MH - *Gene Rearrangement MH - Genetic Predisposition to Disease MH - Humans MH - In Situ Hybridization, Fluorescence MH - Mutation MH - Oncogene Proteins, Fusion/*genetics MH - Phenotype MH - Polymerase Chain Reaction MH - Risk Factors MH - Urinary Bladder Neoplasms/enzymology/*genetics/pathology EDAT- 2013/07/28 06:00 MHDA- 2014/09/30 06:00 CRDT- 2013/07/27 06:00 PHST- 2013/03/15 00:00 [received] PHST- 2013/06/06 00:00 [revised] PHST- 2013/06/06 00:00 [accepted] PHST- 2013/07/27 06:00 [entrez] PHST- 2013/07/28 06:00 [pubmed] PHST- 2014/09/30 06:00 [medline] AID - S0893-3952(22)03604-3 [pii] AID - 10.1038/modpathol.2013.132 [doi] PST - ppublish SO - Mod Pathol. 2014 Jan;27(1):107-12. doi: 10.1038/modpathol.2013.132. Epub 2013 Jul 26.