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Combined Evaluation of Expressions of Cyclin E and p53 Proteins as Prognostic Factors for Patients with Gastric Cancer

Departments of ¹ Surgery, ² Pathology, ³ Public Health, and ⁴ Molecular Biology, King Abdullah University Hospital, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan

Requests for reprints: Kamal E. Bani-Hani, Department of Surgery, Faculty of Medicine, King Abdullah University Hospital, Jordan University of Science and Technology, P.O. Box 3030 Irbid, 22110, Jordan. Phone: 962-79-5500014; Fax: 962-2-7060300; E-mail: banihani60{at}yahoo.com.

Background: There is a lack of consistency regarding the prognostic value of cyclin E overexpression in gastric cancer (gastric cancer). Our aim was to report on this overexpression and to analyze its correlations with the clinicopathologic variables. Another aim was to examine if aberrant expression of both cyclin E and p53 might increase the malignant potential of gastric cancer.

Methods: Specimens from 89 patients with gastric cancer treated with "curative" intent were evaluated for cyclin E and p53 expressions using immunohistochemical method. The correlations between cyclin E overexpression alone or in combination with p53 expression and the patient's clinicopathologic variables were analyzed.

Results: Cyclin E overexpression and p53 expression were shown in 35 (39.3%) and 46 (51.7%) tumors, respectively. The incidence of cyclin E overexpression was significantly higher in deeply invasive cancers (P < 0.0001), in cancers with lymph node metastasis (P = 0.003), and in cancers with advanced stages (P < 0.0001). There were no significant correlations with other clinicopathologic variables. Patients in whom their tumors showed cyclin E overexpression alone or in combination with p53 survived less than patients with negative cyclin E tumors. Multivariate analysis revealed that combined cyclin E overexpression and p53 expression was significantly associated with poor survival after adjusting for other variables (hazard ratio, 3.12; P = 0.009).

Conclusions: Cyclin E overexpression is a common event in gastric cancer. Gastric cancer with cyclin E overexpression exhibit increased aggressiveness in the presence of aberrant p53. The combination of cyclin E overexpression with the p53 expression in gastric cancer further distinguished a subgroup of patients with poor prognosis.

Key Words: Cyclin E • gastric cancer • immunohistochemistry • molecular genetics • prognosis • prognostic marker • p53

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