Affiliations: Department of Oncology, Institute of Biomedicine and
Surgery, Linköping University, 581 85 Linköping, Sweden | Department of Dermatology, Institute of Biomedicine
and Surgery, Linköping University, 581 85 Linköping, Sweden | Department of Surgery, 601 82 Östergötland,
Sweden
Note: [] Corresponding author: Jingfang Gao, Department of Oncology,
Institute of Biomedicine and Surgery, Linköping University, 581 85
Linköping, Sweden. Tel.: +46 13 222840; Fax: +46 13 222846; E-mail:
[email protected]
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.
