Expression of double-stranded RNA-activated protein kinase (PKR) and its prognostic significance in lymph node negative rectal cancer

Abstract

Objective: The interferon-induced, double-stranded RNA-activated, protein kinase (PKR) is a key regulator of translational initiation, and plays an important role in the regulation of cell proliferation, apoptosis and transformation. The aim of this study was to evaluate the prognostic significance of PKR in lymph node negative rectal cancer.

Methods: Forty-three patients with stage II rectal carcinoma who underwent potentially curative resection followed by post-operative adjuvant chemoradiation and 5-fluorouracil-based chemotherapy were investigated immunohistochemically using the monoclonal antibody TJ4C4. Overall scores for PKR expression were calculated based on staining intensity and immunoreactive tumor cell fraction. Clinical information, including tumor grade, carcinoembryonic antigen (CEA), disease-free survival (DFS) and overall survival (OS) was evaluated and compared with the degree of PKR expression.

Results: The median follow-up duration was 53.2 months, and median patient age was 55 years (range 33-73). No relationships were found between PKR score and age, sex, tumor grade or CEA level; however, smaller tumors (< or =5 cm) were associated with high PKR score (P = 0.025). When patients were subdivided into two groups based on the PKR score, the relapse rate was lower for those with a high PKR score (7.4 versus 43.8%, P = 0.008), and a significant difference was found between these two groups in terms of 5 year DFS (92.6 versus 55.6%, P = 0.0072) and 5 year OS (92.6 versus 57.7%, P = 0.0459). Other clinicopathologic variables were not related to clinical outcome.

Conclusion: PKR expression levels were associated with disease recurrence, DFS and OS in lymph node negative rectal cancer patients.