The different roles of hRAD50 in microsatellite stable and unstable colorectal cancers
The different roles of hRAD50 in microsatellite stable and unstable colorectal cancers
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DOI：
10.1155/2008/724796
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发表时间：
2008-01-01
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影响因子：
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通讯作者：
Sun, Xiao-Feng
中科院分区：
文献类型：
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作者：
Gao, Jingfang;Zhang, Hong;Sun, Xiao-Feng
RAD 50蛋白是DNA双链断裂修复和维持基因组完整性所必需的。本研究旨在探讨hRAD 50在微卫星稳定（MSS）和不稳定（MSI）结直肠癌（CRC）中的表达和突变的临床病理意义。应用免疫组化方法检测268例原发结直肠癌、69例癌旁正常黏膜、138例癌旁正常黏膜和44例淋巴结转移癌组织中hRAD 50的表达。采用PCR-SSCP-DNA测序法检测87例原发性CRC中hRAD 50基因突变。与远处/邻近正常粘膜相比，MSS原发性CRC中hRAD 50的表达增加，而MSI原发性CRC中hRAD 50的表达不增加（p < 0.05）。原发性和转移性CRC中hRAD 50的表达无差异。MSS原发性CRC中hRAD 50表达的增加与肿瘤分期早期、分化较好、炎症浸润程度高、p53过表达相关（p <0.05）或倾向于相关（p = 0.05）。hRAD 50编码区（A）9的移码突变仅见于MSI CRC。我们的研究结果表明，hRAD 50可能在MSS和MSI CRC的发展中发挥不同的作用：hRAD 50在MSS CRC中的表达增加可能是对肿瘤进一步发展的细胞反应，而hRAD 50突变可能参与MSI CRC的发展。
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.