title: Evaluation of HER2 protein expression in gastric carcinomas: comparative analysis of 1,414 cases of whole-tissue sections and 595 cases of tissue microarrays.
abstract: BACKGROUND
  Recent advances in molecular targeted therapy have identified HER2 as an important target for anti-cancer therapy in gastric cancer (GC). Although the clinical relevance and prognostic significance of HER2 in breast cancer has been well acknowledged, it remains controversial in GC.
  
  
  METHODS
  HER2 expression was investigated in two independent series of GC by immunohistochemical staining. One series corresponded to 1,414 cases of whole-tissue sections and the other corresponded to 595 cases of tissue microarrays (TMAs). Results were compared and correlated with clinicopathologic parameters.
  
  
  RESULTS
  HER2-positivity was detected in 12.3% of whole-tissue sections and 17% of TMAs. Among samples scored 3+, 90.1% stained ≥50% of the tumor area, but only 40.9% in score 2+ cases stained ≥50% of the tumor area. In whole-tissue sections, HER2-positivity was correlated with age (P = 0.002), histological type (differentiated or intestinal, P < 0.001), lymphovascular invasion (P = 0.005), and lymph node metastasis (P = 0.009). In TMAs, HER2-positivity was correlated only with age (P = 0.003) and histological type (P < 0.001). Multivariate analyses of the differentiated GC subgroup revealed that HER2-positivity was an independent poor prognostic factor (P = 0.042). The cases with HER2-positive in ≥50% of the tumor area showed worse prognosis than those of <50% (P = 0.021).
  
  
  CONCLUSIONS
  Despite discrepancies in the results from whole-tissue sections and TMAs, HER2 overexpression was positively correlated with aggressive biological behavior and was an independent poor prognostic factor for recurrence in differentiated GCs. Therefore, HER2-positive GCs should be considered for adjuvant trastuzumab therapy.
authors.affiliation: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Kab Choong
authors.initials: KC
authors.lastname: Kim
authors.forename: Young Wha
authors.initials: YW
authors.lastname: Koh
authors.forename: Heung-Moon
authors.initials: HM
authors.lastname: Chang
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Kim
authors.forename: Jeong Hwan
authors.initials: JH
authors.lastname: Yook
authors.forename: Byung Sik
authors.initials: BS
authors.lastname: Kim
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Jang
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Park
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005743:Gastrectomy; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015996:Survival Rate; D046888:Tissue Array Analysis; D019043:Vascular Neoplasms / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D055815:Young Adult
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human