REG IV overexpression in an early stage of colorectal carcinogenesis: An immunohistochemical study
REG IV overexpression in an early stage of colorectal carcinogenesis: An immunohistochemical study
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DOI：
10.14670/hh-25.473
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发表时间：
2010-04-01
影响因子：
2
通讯作者：
Takano, Yasuo
中科院分区：
文献类型：
--
作者：
Li, Xiao-Han;Zheng, Yang;Takano, Yasuo
为探讨再生基因（regenerating gene，REG）家族新成员REG IV在结直肠癌（colorectal carcinoma，CRC）发生、发展中的作用，采用免疫组化方法检测320例CRC、123例相应癌旁非癌粘膜（non-adjacent non-cancerous mucosa，ANCM）、46例相应非癌粘膜（non-adjacent non-cancerous mucosa，NANCM）和86例腺瘤中REG IV的表达，并与临床病理特征进行比较。此外，进行双重免疫荧光标记以分析REG IV和肠粘蛋白MUC 2的定位。REG IV在CRCs中的表达显著低于NANCM、ANCM和腺瘤，并且与低分化和静脉浸润呈负相关。在ANCM中，REG IV的表达与肿瘤浸润深度、淋巴结转移及杜克分期呈正相关。CRC中REG IV的表达与MUC 2和Tyr 1068磷酸化EGFR的表达显著相关，但与MUC 5AC、EGFR、Akt或Ser（473）或Thr（308）磷酸化Akt的表达无关。双重免疫荧光显示共表达，但独立的定位，REG IV和MUC 2在NANCM，ANCM，腺瘤和CRC，粘液癌除外。Kaplan-Meier法单因素分析显示REG IV表达与CRC患者的累积生存率无相关性。总之，REG IV的表达在ANCM和腺瘤中上调，然后在CRC中降低。这表明REG IV过表达可能是CRC癌变的早期事件。它在CRC中的表达与MUC 2和Tyr（1068）上EGFR的磷酸化正相关，表明REG IV可能是肠型粘液癌的有用标记物，并且是CRC的分子治疗靶点的良好候选者。
To clarify the role of REG IV, a new member of the regenerating gene (REG) family, in tumorigenesis and progression of colorectal carcinoma (CRC), 320 CRC specimens, 123 corresponding adjacent non-cancerous mucosa (ANCMs), 46 corresponding non-adjacent non-cancerous mucosa (NANCMs) and 86 adenomas were investigated immunohistochemically to compare REG IV expression with clinicopathological features. In addition, double immunofluorescence labeling was performed to analyze the localization of REG IV and the intestinal mucin, MUC2. The expression of REG IV in CRCs was significantly lower than in NANCMs, ANCMs or adenomas, and inversely correlated with poor differentiation and venous invasion. In cases of ANCM, REG IV expression was positively correlated with the depth of invasion, lymph node metastasis and Duke's staging of corresponding cases. The expression of REG IV in CRC was significantly linked to that of MUC2 and the EGFR phosphorylated on Tyr1068, but not to that of MUC5AC, EGFR, Akt, or Akt phosphorylated on Ser(473) or Thr(308). The double immunofluorescence revealed coexpression, but independent localization, of REG IV and MUC2 in NANCMs, ANCMs, adenomas and CRCs, except for mucinous carcinomas. Univariate analysis using the Kaplan-Meier method indicated no correlation between REG IV expression and the cumulative survival rate of CRC patients. In conclusion, REG IV expression was upregulated in ANCMs and adenomas, then decreased in CRCs. This indicated that REG IV overexpression may be an early event in CRC carcinogenesis. Its expression in CRCs was positively linked to MUC2 and phosphorylation of the EGFR on Tyr(1068), suggesting that REG IV may be a useful marker for intestinal type mucinous carcinoma and a good candidate as a molecular therapeutic target for CRCs.