Abstract
BackgroundEsophageal 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.MethodsIn 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.ResultsA 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.ConclusionOverall, 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.
Highlights
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)
epidermal growth factor receptor (EGFR) mutations were analyzed by sequencing exons 18 to 21 in all samples
Four variations (2.6%) were identical to potential or demonstrated activating mutations in EGFR Tyrosine kinase (TK) domain already reported in other cancers, in particular Nonsmall cell lung cancer (NSCLC) (Table 4) and two variations (1.3%) have never been reported in any available database (a onebp deletion in exon 20 (c.2373) and an intronic one
Summary
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. Esophageal Squamous Cell Carcinoma (ESCC) represents about 80% of the cases worldwide and is by far the most common histological type in low-resource countries, whereas adenocarcinoma and women, respectively [7]. In Western countries, ESCC occurs at lower incidence rates (3-20/ 105 person-years) with a male to female ratio of 8–10:1 [2] and frequently develops in subjects with high combined tobacco and alcohol consumption. The etiology of ESCC in central Asia is still largely unknown [5]
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