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Disease Markers
Volume 24, Issue 2, Pages 127-134
http://dx.doi.org/10.1155/2008/724796

The Different Roles of hRAD50 in Microsatellite Stable and Unstable Colorectal Cancers

Jingfang Gao,1 Hong Zhang,2 Gunnar Arbman,3 and Xiao-Feng Sun1

1Department of Oncology, Institute of Biomedicine and Surgery, Linköping University, 581 85 Linköping, Sweden
2Department of Dermatology, Institute of Biomedicine and Surgery, Linköping University, 581 85 Linköping, Sweden
3Department of Surgery, 601 82 Östergötland, Sweden

Received 7 January 2008; Accepted 7 January 2008

Copyright © 2008 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

RAD50 protein is essential for DNA double-strand break repair and maintaining genomic integrity. In this study, we investigated the clinicopathological significance of hRAD50 expression and mutation in microsatellite stable (MSS) and unstable (MSI) colorectal cancers (CRCs). hRAD50 expression was examined in primary CRC (n=268), the corresponding distant (n=69) and adjacent normal mucosa (n=138), and lymph node metastasis (n=44) by immunohistochemistry. hRAD50 mutation was analyzed in 87 primary CRCs by PCR-SSCP-DNA sequencing. hRAD50 expression was increased in MSS primary CRCs, but not MSI ones, compared with distant/adjacent normal mucosa (p<0.05). There was no difference in the hRAD50 expression between primary and metastatic CRCs. The increased hRAD50 expression in MSS primary CRCs was related (p<0.05) or tended to be related (p=0.05) to early tumor stage, better differentiation, high inflammatory infiltration, p53 overexpression. Frameshift mutations of (A)9 at coding region of hRAD50 were only found in MSI CRCs. Our results suggest that hRAD50 may play different roles in the development of MSS and MSI CRCs: increased hRAD50 expression in MSS CRCs may be a cellular response against tumor from further progression, while hRAD50 mutation may be involved in the development of MSI CRCs.