Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the aggressive malignancies and mechanisms underlying its pathogenesis remain unclear. Cyclooxygenase-2 (COX-2) enzyme system plays a crucial role in many gastrointestinal malignancies and is an important regulator of cell growth, proliferation, apoptosis, differentiation and transformation. More precise outcome of COX-2 in ESCC is less investigated. In this study we investigated the risk factors of ESCC and expression of COX-2 in Carcinoma in situ (CIS) and ESCC compared to normal esophageal mucosa. ESCC relationship to clinico-pathological parameters using immunohistochemistry was also part of this investigation. Current study was conducted in the Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan. A total of 69 diagnosed patients of ESCC, both Pakistanis and Afghans were enrolled. Various risk factors associated with ESCC were recorded. Mean age at the time of diagnosis was 55 years. Out of 69 patients of ESCC 46 (67%) were users of dipping tobacco (Naswar). Expression of COX-2 was determined in normal esophageal mucosa, CIS and invasive ESCC using Immunohistochemistry (IHC). Differences of mean were computed using ANOVA followed by applying Post Hoc test. Patients were categorized as positive with high expression or negative with low to nil expression. ANOVA showed large differences in expression of COX-2 in normal healthy mucosa compared with CIS and ESCC with the mean difference of -9.529 and -7.370 respectively, p-value being <.05 at 95% confidence interval (CI). No significant difference was noticed in the expression of COX-2 in CIS compared with ESCC with p-value >.05 at 95% CI. Our complete cohort (23–85 years) showed statistically significant difference in the expression of COX-2 gene in ESCC and CIS tissue samples compared with normal healthy mucosa. Results of this study indicate that over-expression of COX-2 is positively associated with ESCC.

Highlights

  • Esophageal cancer (EC) is a global health concern, ranks eighth among the most common types of cancers and is the 6th most fatal disease worldwide [1,2,3]

  • Low socioeconomic status was observed in 99% of patients

  • Study of the expression pattern of COX-2 in Esophageal squamous cell carcinoma (ESCC) is important to evaluate the role of this gene in the development of cancer and to determine whether COX-2 selective inhibitors would be beneficial for the targeted therapy or not

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Summary

Introduction

Esophageal cancer (EC) is a global health concern, ranks eighth among the most common types of cancers and is the 6th most fatal disease worldwide [1,2,3]. Though significant advances have been made in the treatment of ESCC, yet in many cases, it is still unresponsive to the treatment strategy and has an adverse prognosis, with a five year survival rate of only 10–15% [2, 4]. The most common histological subtype of EC in the high incidence regions such as the greater Iran is ESCC [5, 6], while in the low incidence areas like US, esophageal adenocarcinoma is the most common subtype [7, 8]. Male to female ratio of EC mortality is 2:1 [10]

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