title: Prevalence of HER2 Positivity and Its Clinicopathological Correlation in Locally Advanced/Metastatic Gastric Cancer Patients in Malaysia.
abstract: OBJECTIVE
  Human epidermal growth factor receptor 2 (Erbb2/HER2) overexpression, which was previously detected in invasive breast cancer, has now been implicated in advanced gastric cancer (GC) and gastroesophageal junction cancer (GEC). A study was conducted to determine the rate of HER2 positivity in patients with locally advanced or metastatic GC and GEC in Malaysia and to assess the impact of various demographic and clinical parameters on HER2 positivity.
  
  
  METHODS
  A total of 228 adult patients with GC or GEC were enrolled from Subang Jaya Medical Centre, Malaysia, for retrospective (210) and prospective study. All patients were subjected to the HER2 immunohistochemistry test using an FDA-approved, standardized test kit. Carcinomas scoring 2+ on immunohistochemistry were further tested with HER2 in situ hybridization (ISH) using an FDA-approved test kit.
  
  
  RESULTS
  The overall rate of HER2 positivity in the population studied was 24.6% (n = 56). The rate was significantly higher in men than in women (29.6 vs. 16.3%; p = 0.024). HER2 overexpression was significantly more common in diffuse type than in intestinal type of tumors (39.8 vs. 14.9%; p < 0.001). In our study, out of 56 samples, 44 (78.6%) were considered for gene amplification testing, out of which 40 (90.1%) samples showed gene amplification. There was no statistically significant correlation between HER2 positivity and patient age, race, tumor location, tumor differentiation, and TNM staging.
  
  
  CONCLUSIONS
  HER2 overexpression was evident in nearly 25% of the Malaysian patients with locally advanced or metastatic gastric cancer. The overexpression correlated significantly with male gender and diffuse-type tumors. The majority of the IHC-positive tumors demonstrated c-erb2 gene amplification and this finding reached statistical significance.
authors.affiliation: Department of Pathology, Subang Jaya Medical Centre, Subang Jaya, Sunway Medical Centre, Monash University Malaysia, 1, Jalan SS 12/1A, 47500, Subang Jaya, Selangor, Malaysia. drpathma@gmail.com.
authors.forename: Pathmanathan
authors.initials: P
authors.lastname: Rajadurai
authors.affiliation: Mount Miriam Cancer Hospital, Tanjung Tokong, Penang, Malaysia.
authors.forename: Ho Kean
authors.initials: HK
authors.lastname: Fatt
authors.affiliation: Subang Jaya Medical Centre, Subang Jaya, Selangor, Malaysia.
authors.forename: Foo Yoke
authors.initials: FY
authors.lastname: Ching
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008296:Malaysia / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D015995:Prevalence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: DISH; Gastric cancer; Gastroesophageal junction cancer; Genes; HER2; Immunohistochemistry; Malaysia