Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama 930-0194, Japan.
Histol Histopathol. 2010 Apr;25(4):473-84. doi: 10.14670/HH-25.473.
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 Ser473 or Thr308. 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 Tyr1068, 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.
为了阐明 REG IV（REG 家族的新成员）在结直肠癌（CRC）发生和进展中的作用，我们应用免疫组化方法检测了 320 例 CRC 标本、123 例相应的癌旁非肿瘤黏膜（ANCM）、46 例相应的非旁非肿瘤黏膜（NANCM）和 86 例腺瘤中 REG IV 的表达情况，并与临床病理特征进行了比较。此外，还进行了双重免疫荧光标记，以分析 REG IV 与肠道黏蛋白 MUC2 的定位。结果显示，CRC 中 REG IV 的表达明显低于 NANCM、ANCM 或腺瘤，且与分化不良和静脉浸润呈负相关。在 ANCM 中，REG IV 的表达与相应病例的浸润深度、淋巴结转移和 Duke 分期呈正相关。CRC 中 REG IV 的表达与 MUC2 和 EGFR 磷酸化 Tyr1068 显著相关，但与 MUC5AC、EGFR、Akt 或 Akt 磷酸化 Ser473 或 Thr308 无关。双重免疫荧光显示，除黏液性腺癌外，REG IV 和 MUC2 在 NANCM、ANCM、腺瘤和 CRC 中均呈共表达，但定位独立。Kaplan-Meier 单因素分析表明，REG IV 表达与 CRC 患者的累积生存率无关。总之，REG IV 的表达在 ANCM 和腺瘤中上调，而在 CRC 中下调。这表明 REG IV 过表达可能是 CRC 癌变的早期事件。其在 CRC 中的表达与 MUC2 和 EGFR 磷酸化 Tyr1068 呈正相关，提示 REG IV 可能是肠型黏液腺癌的有用标志物，也是 CRC 的一个潜在治疗靶点。
