title: Epidermal growth factor receptor (EGFR) mutations and expression in squamous cell carcinoma of the esophagus in central Asia.
abstract: BACKGROUND
  Esophageal squamous cell carcinoma (ESCC) shows geographic variations in incidence, with high incidences (>50/105 person-years) in central Asia, including North Eastern Iran (Golestan) and Northern India (Kashmir). In contrast to Western countries, smoking does not appear to be a significant risk factor for ESCC in central Asia. In lung adenocarcinoma, activating mutations in the gene encoding epidermal growth factor receptor (EGFR) are frequent in tumors of never smokers of Asian origin, predicting therapeutic sensitivity to Egfr-targeting drugs.
  
  
  METHODS
  In this study 152 cases of histologically confirmed ESCC from Iran (Tehran and Golestan Province) and North India (Kashmir Valley) have been analyzed for EGFR mutation by direct sequencing of exons 18-21. Egfr protein expression was evaluated by immunohistochemistry in 34 samples from Tehran and HER2 mutations were analyzed in 54 cases from Kashmir.
  
  
  RESULTS
  A total of 14 (9.2%) EGFR variations were detected, including seven variations in exons. Among those, four (2.6%) were already documented in lung cancers, two were reported as polymorphisms and one was a potentially new activating mutation. All but one variation in introns were previously identified as polymorphisms. Over-expression of Egfr was detected in 22/34 (65%) of tested cases whereas no HER2 mutation was found in 54 cases from Kashmir.
  
  
  CONCLUSIONS
  Overall, EGFR mutations appear to be a rare event in ESCC in high incidence areas of central Asia, although a very small proportion of cases may harbor mutations predicting sensitivity to anti-Egfr drugs.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Behnoush
authors.initials: B
authors.lastname: Abedi-Ardekani
authors.forename: Nazir Ahmad
authors.initials: NA
authors.lastname: Dar
authors.forename: Mohammad Muzaffar
authors.initials: MM
authors.lastname: Mir
authors.forename: Showkat Ahmad
authors.initials: SA
authors.lastname: Zargar
authors.forename: M Muqbool
authors.initials: MM
authors.lastname: Lone
authors.forename: Ghyslaine
authors.initials: G
authors.lastname: Martel-Planche
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Villar
authors.forename: Mounia
authors.initials: M
authors.lastname: Mounawar
authors.forename: Farrokh
authors.initials: F
authors.lastname: Saidi
authors.forename: Reza
authors.initials: R
authors.lastname: Malekzadeh
authors.forename: Pierre
authors.initials: P
authors.lastname: Hainaut
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001209:Asia, Central; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018773:Genes, erbB-1; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C512478:EGFR protein, human; D066246:ErbB Receptors