Publication: RAD50-MRE11-NBS1 proteins in relation to tumour development and prognosis in patients with microsatellite stable colorectal cancer
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Date
2008
Authors
Gao, Jingfang ; Zhang, Hong ; Arbman, Gunnar ; Sun, Xiao-Feng
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
RAD50/MRE11/NBS1 complex is essential
for DNA double-strand break repair and for maintaining
genomic integrity. In this study, we immunohistochemically
examined MRE11, NBS1 and RAD50
expression in primary CRCs (n=208), the corresponding
distant (n=41) and adjacent normal mucosa (n=130), and
lymph node metastases (n=26), and investigated their
clinicopathological significance in colorectal cancers
(CRCs). We found that the intensity and percentage of
MRE11 and NBS1 in primary CRCs were positively
correlated with each other and with RAD50 (P<0.0001).
Strong expression of MRE11, NBS1 or combined
RAD50/MRE11/NBS1 was related to MSS, positive
hMLH1 expression, earlier tumour stage (TNM stage I
and II) and favourable survival (P<0.05). A high
percentage of MRE11 expression was associated with
less local recurrence and high apoptotic activity
(P<0.05). In MSS CRCs, the expression of MRE11 and
NBS1 was stronger than that in normal mucosa
(P<0.05), and strong expression of NBS1 in primary
tumour was related to favourable survival of patients in TNM stage I and II (univariate analysis: P=0.03;
multivariate analysis: P=0.07). In MSI CRCs, neither
MRE11 nor NBS1 expression showed differences among
normal mucosa, primary tumour and metastasis, or
among clinicopathological variables. In conclusion,
RAD50/MRE11/NBS1 proteins interacted with each
other, which had different clinicopathological
significance in MSS and MSI CRCs, and further, each
component of the complex might have additional roles.
NBS1 might be a prognostic factor for patients with
MSS tumour in TNM stage I and II.
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