Clinicopathological characteristics of colorectal cancers with loss of imprinting of insulin‐like growth factor 2
Clinicopathological characteristics of colorectal cancers with loss of imprinting of insulin‐like growth factor 2
复制标题
DOI：
10.1002/ijc.21741
复制
发表时间：
2006-07
影响因子：
6.4
通讯作者：
J. Sasaki;F. Konishi;Y. Kawamura;Toshihiro Kai;Osamu Takata;T. Tsukamoto
中科院分区：
文献类型：
--
作者：
J. Sasaki;F. Konishi;Y. Kawamura;Toshihiro Kai;Osamu Takata;T. Tsukamoto
据报道，印记丢失（LOI），即胰岛素样生长因子2（IGF2）印记基因的双等位基因表达，与结直肠癌发生有关，因为它在正常结直肠粘膜以及结直肠癌患者的癌组织中普遍存在。然而，与IGF2 LOI相关的结直肠癌特征尚未得到明确证实。在这项研究中，我们调查了 255 名连续结直肠癌患者的肿瘤和正常粘膜的 IGF2 LOI 状态。通过 IGF2 mRNA 的直接测序，其中 95 个可提供 IGF2 LOI 信息。关于每位患者的 LOI 状态，LOI 阳性癌症患者的非肿瘤正常粘膜中 LOI 的患病率显着高于 LOI 阴性癌症患者 (p < 0.001)。关于LOI阳性癌症的临床病理特征，低分化癌或粘液癌（p = 0.016）和右侧位置癌（p = 0.009）的患病率显着高于LOI阴性癌症。过去的报告显示，在相对较小的非队列患者中，微卫星不稳定性（MSI）与 IGF2 LOI 之间存在显着相关性，与此相反，我们的研究没有发现 MSI 阳性和阴性病例之间的 LOI 阳性率存在统计学上的显着差异。我们的结果表明存在一种特定类型的结直肠癌，与近端结肠和分化差相关，但与 MSI 无关。这些结果可能有助于阐明结直肠肿瘤发生机制并确定适当的结直肠癌筛查策略。 © 2006 Wiley-Liss, Inc.
Loss of imprinting (LOI), the biallelic expression of an imprinting gene, of insulin‐like growth factor 2 (IGF2) has been reported to be associated with colorectal carcinogenesis because of its high prevalence in normal colorectal mucosa as well as cancerous tissue in patients with colorectal cancer. However, the characteristics of colorectal cancer associated with IGF2 LOI have not been clearly demonstrated. In this study, we investigated the IGF2 LOI status of tumor and normal mucosa in 255 consecutive patients with colorectal cancer. Of these, 95 were informative for IGF2 LOI, by direct sequencing of mRNA of IGF2. Regarding the LOI status in each patient, the prevalence of LOI in nontumorus normal mucosa was significantly higher in cases with LOI‐positive cancer than in those with LOI‐negative cancer (p < 0.001). Concerning the clinicopathological characteristics of LOI‐positive cancer, the prevalence of poorly differentiated or mucinous carcinoma (p = 0.016) and of right‐sided locations (p = 0.009) were significantly higher than those of LOI‐negative cancer. Contrary to past reports that revealed a significant correlation between microsatellite instability (MSI) and IGF2 LOI in a relatively small series of noncohort patients, our study did not find a statistically significant difference in LOI‐positive rate between MSI‐positive and ‐negative cases. Our results suggested the presence of a particular type of colorectal cancer associated with the proximal colon and poor differentiation, but independent of MSI. These results may contribute to clarification of the mechanism of colorectal tumorigenesis and to determining an appropriate screening strategy for colorectal carcinoma. © 2006 Wiley‐Liss, Inc.