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Japanese Journal of Clinical Oncology Advance Access published online on September 7, 2005
Japanese Journal of Clinical Oncology, doi:10.1093/jjco/hyi146
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© 2005 Foundation for Promotion of Cancer Research
Received March 10, 2005
Accepted July 20, 2005

Original Article

Expression of Double-stranded RNA-activated Protein kinase (PKR) and its Prognostic Significance in Lymph Node Negative Rectal Cancer

Hyuk-Chan Kwon 1, Chang Hoon Moon 1, Sung-Hyun Kim 1, Hong-Jo Choi 2, Hyung-Sik Lee 3, Mee Sook Roh 4, Tae-Ho Hwang 5, Jae-Seok Kim 1, and Hyo-Jin Kim 1*

1 Department of Internal Medicine, Dong-A University, College of Medicine, Busan, Korea
2 Department of Surgery, Dong-A University, College of Medicine, Busan, Korea
3 Department of Radiation Oncology, Dong-A University, College of Medicine, Busan, Korea
4 Department of Pathology, Dong-A University, College of Medicine, Busan, Korea
5 Department of Pharmacology, Dong-A University, College of Medicine, Busan, Korea

* To whom correspondence should be addressed.
Hyo-Jin Kim, E-mail: kimhj{at}dau.ac.kr


  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 (≤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.

Keywords: PKR; rectal cancer; immunohistochemistry; prognosis.
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