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

• Published in: Journal of gastroenterology and hepatology 2011-02, Vol.26 (2), p.382-390
• Main Authors: Parthasarathy, Seshacharyulu, Dhayaparan, Devaraj, Jayanthi, Venkatraman, Devaraj, Sivasitambaram Niranjali, Devaraj, Halagowder
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Alcohol Drinking - adverse effects; Biological and medical sciences; Biopsy; Blotting, Western; Carcinoma, Squamous Cell - enzymology; Carcinoma, Squamous Cell - pathology; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Chi-Square Distribution; Dermatology; dysplasia; epidermal growth factor receptor; Esophageal Neoplasms - enzymology; Esophageal Neoplasms - pathology; Esophagitis - enzymology; Esophagitis - pathology; Esophagus - enzymology; Esophagus - pathology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immunohistochemistry; Immunoprecipitation; India; Male; Medical sciences; Middle Aged; Mitogen-Activated Protein Kinase 1 - analysis; Mitogen-Activated Protein Kinase 3 - analysis; Neoplasm Staging; NF-kappa B - analysis; p38 Mitogen-Activated Protein Kinases - analysis; Phosphorylation; Precancerous Conditions - enzymology; Precancerous Conditions - pathology; protein kinase C δ; Protein Kinase C-delta - analysis; Receptor, Epidermal Growth Factor - analysis; Risk Assessment; Risk Factors; Smoking - adverse effects; squamous cell carcinoma; Tumor Necrosis Factor-alpha - analysis; Tumors of the skin and soft tissue. Premalignant lesions
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1111/j.1440-1746.2010.06526.x

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