title: Heterogeneous amplification of ERBB2 in primary lesions is responsible for the discordant ERBB2 status of primary and metastatic lesions in gastric carcinoma.
abstract: OBJECTIVE
  To determine the extent of HER2 homogeneity/heterogeneity in primary versus metastatic gastric carcinoma (GC).
  
  
  RESULTS
  The human epidermal growth factor receptor 2 (HER2) status in primary and metastatic lesions was evaluated by immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH). Four separate cohorts consisting of primary GC alone or primary GC paired with metastatic lesions were examined. In the FISH analysis of 325 primary GCs, eight cases (2.5%) showed amplification with a heterogeneous pattern, whereas 27 cases (8.3%) showed amplification with a homogeneous pattern, and in this cohort the discordant:concordant FISH ratio based on examination of three different areas in each primary lesion was 0.30:1. FISH testing using 250 paired primary and metastatic lesions revealed seven cases (2.8%) with discordant amplification. In metastatic disease positive conversion occurred in six cases (2.4%), whereas negative conversion happened in one case (0.4%). The discordant:concordant ratio of primary versus secondary lesions was 0.23:1. When the seven discordant cases were re-evaluated using whole sections of primary GCs, six showed a heterogeneous pattern of amplification.
  
  
  CONCLUSIONS
  These findings suggest that the discordant HER2 amplification observed in metastatic lesions is explained substantially by heterogeneity within primary tumours.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Min A
authors.initials: MA
authors.lastname: Kim
authors.forename: Hyuk-Joon
authors.initials: HJ
authors.lastname: Lee
authors.forename: Han-Kwang
authors.initials: HK
authors.lastname: Yang
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
references.citation: Histopathology. 2008 Jun;52(7):797-805
references.pmid: 18422971
references.citation: Cancer. 2005 May 1;103(9):1763-9
references.pmid: 15786420
references.citation: Hum Pathol. 2007 Sep;38(9):1386-93
references.pmid: 17555797
references.citation: Hum Pathol. 2009 Mar;40(3):314-22
references.pmid: 18835621
references.citation: Cancer. 2002 Apr 15;94(8):2169-73
references.pmid: 12001113
references.citation: Ann Oncol. 2005 Feb;16(2):273-8
references.pmid: 15668283
references.citation: Ann Oncol. 2002 Jul;13(7):1036-43
references.pmid: 12176781
references.citation: Virchows Arch. 2004 Sep;445(3):255-62
references.pmid: 15517369
references.citation: Hum Pathol. 2004 Mar;35(3):379-81
references.pmid: 15017597
references.citation: J Clin Oncol. 2007 Jan 1;25(1):118-45
references.pmid: 17159189
references.citation: N Engl J Med. 2005 Oct 20;353(16):1673-84
references.pmid: 16236738
references.citation: Oncol Rep. 2006 Jan;15(1):65-71
references.pmid: 16328035
references.citation: Int J Cancer. 2008 Mar 1;122(5):999-1004
references.pmid: 17973263
references.citation: J Natl Cancer Inst. 2001 Aug 1;93(15):1141-6
references.pmid: 11481385
references.citation: Ann Oncol. 2008 Mar;19(3):596-597
references.pmid: 32560012
references.citation: Am J Clin Pathol. 1999 Jul;112(1 Suppl 1):S53-67
references.pmid: 10396301
references.citation: Hum Pathol. 2009 Jun;40(6):769-77
references.pmid: 19269014
references.citation: N Engl J Med. 2005 Oct 20;353(16):1659-72
references.pmid: 16236737
references.citation: Science. 1986 Jun 27;232(4758):1644-6
references.pmid: 3012781
references.citation: N Engl J Med. 2001 Mar 15;344(11):783-92
references.pmid: 11248153
references.citation: Br J Cancer. 2004 Jun 14;90(12):2344-8
references.pmid: 15150568
references.citation: Br J Cancer. 2005 Sep 5;93(5):552-6
references.pmid: 16106267
references.citation: Cancer. 1999 May 1;85(9):1894-902
references.pmid: 10223227
references.citation: Proc Natl Acad Sci U S A. 1984 Dec;81(23):7308-12
references.pmid: 6095284