Ronnett B M, Burks R T, Cho K R, Hedrick L
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Mod Pathol. 1997 Jan;10(1):38-46.
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.
结直肠癌缺失基因（DCC）是一个候选抑癌基因，位于18号染色体长臂。DCC最初是在寻找位于18q区域的目标基因时被鉴定和克隆的，该区域在70%至80%的结直肠癌中显示杂合性缺失（LOH）。最近，含有DCC基因的18q区域在大约14%至30%的子宫内膜癌中显示出杂合性缺失。这些发现表明，DCC可能至少在一些子宫内膜癌中是杂合性缺失的靶点，因此，可能在这种女性生殖道常见恶性肿瘤的发病机制中起作用。为了探究这种可能性，我们分析了26例子宫内膜样腺癌的DCC杂合性缺失情况以及位于DCC基因一个内含子中的AT微卫星重复序列的改变。在1例（4%）中检测到杂合性缺失。在另外5例（19%）中检测到DCC基因AT重复序列的等位基因移位。我们还通过免疫组化分析评估了正常、增生和肿瘤性子宫内膜组织中DCC蛋白的表达。3例增殖期和5例分泌期子宫内膜以及1例单纯性子宫内膜增生显示有DCC染色。在可获得冷冻组织的26例子宫内膜样腺癌中，有4例，包括每个组织学分级至少1例，以及1例局限于子宫内膜的子宫内膜样癌完全缺乏可检测到的DCC染色。虽然DCC杂合性缺失在子宫内膜癌中不常见，但该基因的改变（杂合性缺失或AT重复序列改变）并不罕见（我们的病例中有23%）。此外，DCC在正常子宫内膜组织中表达，而在所有5例子宫内膜癌中均未表达。基因改变和DCC蛋白表达缺失表明，DCC基因的失活可能在子宫内膜癌的发病机制中起作用。
