The different roles of hRAD50 in microsatellite stable and unstable colorectal cancers.
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.
Gao
Jingfang
J
Department of Oncology, Institute of Biomedicine and Surgery, Linköping University, 581 85 Linköping, Sweden. jinga@ibk.liu.se
Zhang
Hong
H
Arbman
Gunnar
G
Sun
Xiao-Feng
XF
D017766:Acid Anhydride Hydrolases; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D053903:DNA Breaks, Double-Stranded; D045643:DNA Repair Enzymes / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged
D004268:DNA-Binding Proteins; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes