P53, COX-2, iNOS protein expression changes and their relationship with anti-oxidant enzymes in surgically and...

Esophageal carcinoma has a high incidence in India but its etiology remains unknown. In the present study the correlation between apoptosis regulatory proteins and anti-oxidant enzymes in 40 esophageal carcinoma patients was examined. Patients in one group were operated by transhiatal esophagectomy and in the second group were administered cisplatin (30 mg/m2/day) and 5-fluorouracil (5-FU) (750 mg/m2/day) daily for three days followed by surgery after four weeks of neo-adjuvant therapy (NAT). Complete pathological response was achieved in 15% of patients. Results obtained by Western blot analysis showed over-expressed p53 and COX-2 protein levels in the tumor tissues as compared to the adjoining tissue and its paired normal mucosa in both groups of patients. Immunohistochemical studies showed heterogenous p53 staining pattern with sections showing both nuclear and cytoplasmic staining with 36.8% mild, 10.5% moderate and 52.6% intense p53 immunoreactivity. Both COX-2 and iNOS immunostaining revealed 25% negative and 75% mild to strongly positive immunoreactivity. Correlation studies demonstrated a positive relationship between p53 and COX-2 (P=0.030; r = +0.70) in surgically treated patients. The association of COX-2 and p53 with various anti-oxidant enzymes showed a significantly positive correlation between COX-2 expression and catalase activity and an inverse correlation between p53 expression and superoxide dismutase and catalase activity in the tumor tissue of patients given NAT. In addition, we observed a negative trend between p53 expression levels and GPx enzyme levels in both the adjoining and tumor tissue of patients having undergone surgery as main mode of treatment.