Aberrant expression of epidermal growth factor receptor and its interaction with protein kinase C δ in inflammation associated neoplastic transformation of human esophageal epithelium in high risk populations


Professor Halagowder Devaraj, Department of Zoology, University of Madras, Guindy Campus, Chennai 600025, Tamilnadu, India. Email: hdrajum@yahoo.com


Background and Aim:  Esophageal cancer is the second most common cancer among Indian males and is mostly associated with tobacco smoking and alcohol consumption. Epidermal growth factor receptor (EGFR) is a member of Type I tyrosine kinases. Its activation causes the docking of various proteins in its cytosolic tail. In the present study we have analyzed the expression pattern of EGFR, protein kinase C δ (PKCδ), tumor necrosis factor-α (TNF-α), nuclear factor κB (NFκB) and the interactions between EGFR and PKCδ in various pathological conditions.

Methods:  Human esophageal biopsies were obtained from 93 patients with a past history of smoking and alcohol consumption: 20 showed normal mucosa, 40 with dysplasia and 33 squamous cell carcinoma (SCC). These pathological conditions were analyzed immunohistochemically for the presence of EGFR expression and then subsequently analyzed using immunoblot and immunoprecipitation.

Results:  A statistically significant difference of EGFR overexpression was found between low- and high-grade dysplasia and carcinoma (χ2 = 3.3, χ2 = 3.42: P = 0.07, 0.33). A statistical significance was observed between dysplasia and SCC and in all histopathological types (χ2 = 4, χ2 = 4.9; P < 0.05, P = 0.18 and χ2 = 26.3, 26.6; P < 0.001). EGFR tyrosine phosphorylation and its association with PKCδ was significantly higher in all histopathological types with χ2 = 7.965; P < 0.05 and 4.0830; P = 0.2530.

Conclusion:  Altogether, our findings reveal that the activation of EGFR and its subsequent interaction with PKCδ under inflammatory conditions might positively be attributed to the transformation of normal esophageal epithelia to SCC, which could explain ongoing inflammation in normal mucosa in a population prone to smoking and alcoholism.