title: HER-2 is an independent prognostic factor in endometrial cancer: association with outcome in a large cohort of surgically staged patients.
abstract: OBJECTIVE
  To evaluate HER-2 expression and amplification in a large cohort of endometrial cancer with complete surgical staging and outcome data.
  
  
  METHODS
  A tissue microarray was constructed of 483 patients with endometrial cancer of diverse histologic type and stage and tested for HER-2 expression and amplification using current standards of practice. There was outcome data for 83% of all patients and 81% with complete surgical staging.
  
  
  RESULTS
  Both expression and amplification of HER-2 was associated with high-grade (P = .0001) and high stage (P = .0001) endometrial cancer. The highest rate of HER-2 expression and amplification was seen in serous carcinoma (43% and 29%), while grade 1 endometrioid adenocarcinoma showed the lowest levels (3% and 1%). For all histologic types, the rate of HER-2 expression and amplification was remarkably different (P < .0001) for grade 3 cancers (31% and 15%) versus grade 2 (7% and 3%) and grade 1 cancers (3% and 1%), with similar results for endometrioid type (P < .0001). Both HER-2 expression and amplification correlated with disease-specific survival and progression-free survival in univariate analyses. By multivariate analysis HER-2 expression in the presence of amplification (P = .012) correlated with overall survival, but not expression in the absence of amplification. Overall survival was significantly shorter (P = .0001) in patients who overexpressed (median, 5.2 years) and/or showed amplification of HER-2 (median, 3.5 years) versus those that did not (median of all cases, 13 years).
  
  
  CONCLUSIONS
  Our results would suggest that HER-2 is an important oncogene in high grade and stage endometrial cancer, but plays only a minor role in the much more common low grade and stage tumors that encompass the majority of clinical practice.
authors.affiliation: Department of Pathology, Division of Gynecologic Oncology Center for Biostatistics, The Arthur James Cancer Hospital, and the Richard Solove Research Institute, The Ohio State University Medical School Columbus, OH 43210, USA. morrison4@medctr.osu.edu
authors.forename: Carl
authors.initials: C
authors.lastname: Morrison
authors.forename: Vanna
authors.initials: V
authors.lastname: Zanagnolo
authors.forename: Nilsa
authors.initials: N
authors.lastname: Ramirez
authors.forename: David E
authors.initials: DE
authors.lastname: Cohn
authors.forename: Nicole
authors.initials: N
authors.lastname: Kelbick
authors.forename: Larry
authors.initials: L
authors.lastname: Copeland
authors.forename: G Larry
authors.initials: GL
authors.lastname: Maxwell
authors.forename: Larry G
authors.initials: LG
authors.lastname: Maxwell
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Fowler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D015331:Cohort Studies; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000628:therapy*; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D018734:Genes, erbB-2 / Q000235:genetics*; D013509:Gynecologic Surgical Procedures; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D015995:Prevalence; D011379:Prognosis; D011878:Radiotherapy; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor