title: A subset of pancreatic adenocarcinomas demonstrates coamplification of topoisomerase IIalpha and HER2/neu: use of immunolabeling and multicolor FISH for potential patient screening andtreatment.
abstract: We sought to identify the frequency of amplification of the topoisomerase IIalpha gene (TOP2A) in pancreatic cancer and determine the usefulness of TOP2A immunolabeling in screening for TOP2A and human epidermal growth factor receptor (HER)2/neu amplification. We examined 55 pancreatic adenocarcinoma specimens for TOP2A immunolabeling and identified TOP2A protein expression in all specimens with a nuclear labeling index (NLI; positive nuclei/total nuclei x 100) of 5% to 80%. Normal pancreatic ductal epithelium, proposed to give rise to pancreatic adenocarcinoma, did not demonstrate detectable TOP2A expression. In a subset of specimens selected for fluorescence in situ hybridization analysis of TOP2A and HER2/neu amplification using a recently developed multicolor probe, 7 of 8 lesions with an NLI of 25% or more demonstrated TOP2A amplification, in contrast with 2 of 14 lesions with a TOP2A NLI of less than 25%. In 8 of 9 TOP2A-amplified cases, coamplification of HER2/neu was present, suggesting a potential relationship between TOP2A and HER2/neu in pancreatic adenocarcinoma. We propose that TOP2A immunolabeling be used in conjunction with a newly developed multicolor probe to screen patients with pancreatic adenocarcinoma to determine the best potential therapeutic modalities, such as TOP2A inhibitors, trastuzumab, or both.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institution, Baltimore, MD, USA.
authors.forename: Donna E
authors.initials: DE
authors.lastname: Hansel
authors.forename: Raheela
authors.initials: R
authors.lastname: Ashfaq
authors.forename: Ayman
authors.initials: A
authors.lastname: Rahman
authors.forename: Dana
authors.initials: D
authors.lastname: Wanzer
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Yeo
authors.forename: Robb E
authors.initials: RE
authors.lastname: Wilentz
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm; D004250:DNA Topoisomerases, Type II / Q000032:analysis / Q000235:genetics*; D004268:DNA-Binding Proteins; D005784:Gene Amplification; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis
chemical_list: D000951:Antigens, Neoplasm; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C000618811:TOP2A protein, human