DCC genetic alterations and expression in endometrial carcinoma.
DCC genetic alterations and expression in endometrial carcinoma.
复制标题
DOI：
--
复制
发表时间：
1997
期刊：
影响因子：
--
通讯作者：
B. Ronnett;R. Burks;K. Cho;L. Hedrick
中科院分区：
文献类型：
--
作者：
B. Ronnett;R. Burks;K. Cho;L. Hedrick
DCC基因是位于18号染色体长臂上的一个候选抑癌基因。DCC最初是在寻找位于18 q区域的靶基因的过程中被鉴定和克隆的，该区域在70 - 80%的结直肠癌中表现出杂合性缺失（洛）。最近，18 q区域的DCC基因已被证明经历洛在约14至30%的子宫内膜癌。这些结果表明，DCC可能是洛缺失的目标，至少在一些子宫内膜癌，因此，可能有一个作用，在发病机制中的这种常见的恶性肿瘤的女性生殖道。为了解决这种可能性，我们分析了26例子宫内膜样癌的DCC洛缺失和DCC基因内含子中AT微卫星重复序列的改变。洛缺失1例（4%）。在DCC AT重复的等位基因转移中检测到另外5例（19%）。我们还通过免疫组化分析评价了DCC蛋白在正常、增生和肿瘤子宫内膜组织中的表达。3例增殖期子宫内膜、5例分泌期子宫内膜和1例单纯性子宫内膜增生症显示DCC染色。26例子宫内膜样癌中有4例可获得冷冻组织，包括每种组织学分级至少1例，1例局限于子宫内膜的子宫内膜样癌完全缺乏可检测的DCC染色。虽然DCC洛缺失在子宫内膜癌中并不常见，但该基因的改变（洛或AT重复序列改变）并不少见（占我们病例的23%）。此外，DCC在正常子宫内膜组织中表达，而在所有5例子宫内膜癌中均表达缺失。DCC蛋白表达缺失和基因改变的结合提示DCC基因的失活可能在子宫内膜癌的发病机制中起作用。
DCC (Deleted in Colorectal Carcinoma) is a candidate tumor suppressor gene located on the long arm of chromosome 18. DCC was initially identified and cloned during a search for the target gene located in a region of 18q that demonstrated loss of heterozygosity (LOH) in 70 to 80% of colorectal cancers. More recently, the region of 18q harboring the DCC gene has been shown to undergo LOH in approximately 14 to 30% of endometrial carcinomas. These findings suggest that DCC may be a target of LOH in at least some endometrial carcinomas and, therefore, may have a role in the pathogenesis of this common malignancy of the female genital tract. To address this possibility, we analyzed 26 cases of endometrioid endometrial carcinoma for DCC LOH and alterations in an AT microsatellite repeat located in an intron of the DCC gene. LOH was detected in one case (4%). Allelic shifts at the DCC AT repeat were detected in five (19%) additional cases. We also evaluated DCC protein expression by immunohistochemical analysis in normal, hyperplastic, and neoplastic endometrial tissues. Three proliferative and five secretory endometria and one simple endometrial hyperplasia demonstrated staining for DCC. Four of the 26 endometrioid endometrial carcinomas for which frozen tissue was available, including at least one from each histologic grade, and a case of endometrioid carcinoma confined to the endometrium completely lacked detectable staining for DCC. Although DCC LOH was infrequent in endometrial carcinomas, alterations of the gene (LOH or AT repeat alterations) were not uncommon (23% of our cases). In addition, DCC was expressed in normal endometrial tissue, whereas expression was lost in all of the five endometrial carcinomas. The combination of the genetic alterations and loss of DCC protein expression suggests that inactivation of the DCC gene may play a role in the pathogenesis of endometrial carcinoma.