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Open Access Research article

Epidermal growth factor receptor (EGFR) mutations and expression in squamous cell carcinoma of the esophagus in central Asia

Behnoush Abedi-Ardekani123, Nazir Ahmad Dar14, Mohammad Muzaffar Mir58, Showkat Ahmad Zargar6, M Muqbool Lone7, Ghyslaine Martel-Planche1, Stéphanie Villar1, Mounia Mounawar19, Farrokh Saidi2, Reza Malekzadeh2 and Pierre Hainaut110*

Author Affiliations

1 International Agency for Research on Cancer, Lyon, France

2 Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

3 Social security Organization, Tehran, Iran

4 Department of Biochemistry, University of Kashmir, Srinagar, India

5 Departments of Clinical Biochemistry, SK-Institute of Medical Sciences, Soura Srinagar, JK, India

6 Department of Gastroenteriology, SK-Institute of Medical Sciences, Soura Srinagar, JK, India

7 Department of Radiation Oncology, SK-Institute of Medical Sciences, Soura Srinagar, JK, India

8 College of Medicine, Al Jouf University, Sakaka, Al Jouf, 75471, KSA

9 Institute for Cancer Research, Chester Beaty Laboratories, London, UK

10 International Prevention Research Institute, Lyon, France

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BMC Cancer 2012, 12:602  doi:10.1186/1471-2407-12-602

Published: 17 December 2012

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.

Conclusion

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.

Keywords:
Squamous cell carcinoma; Esophagus; EGFR mutations; Golestan; Kashmir