Novel molecular profiles of endometrial cancer - new light through old windows
Novel molecular profiles of endometrial cancer - new light through old windows
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DOI：
10.1016/j.jsbmb.2007.09.020
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发表时间：
2008-02-01
影响因子：
4.1
通讯作者：
Reventos, J.
中科院分区：
文献类型：
--
作者：
Doll, A.;Abal, M.;Reventos, J.
子宫内膜癌是西方国家最常见的妇科恶性肿瘤。一个被广泛接受的二元模型已经建立在形态学的基础上，将EC分为两大类：I型雌激素依赖型腺癌和II型非雌激素依赖型EC，前者具有子宫内膜样形态，后者具有浆液性乳头状或透明细胞形态。分子遗传学证据表明，与其他恶性肿瘤一样，子宫内膜癌的发生可能是由于细胞调控途径的改变逐步积累的结果，如癌基因激活和抑癌基因失活，导致细胞生长功能障碍。在I型子宫内膜样癌中，PTEN基因沉默和DNA错配修复基因缺陷，如微卫星不稳定性表型，或K-ras和/或β-catenin基因突变，被认为是主要的改变，定义了正常子宫内膜向增生、子宫内膜上皮内瘤变和癌症的发展。相比之下，II型癌症表现为TP53和HER-2/neu突变，似乎起源于萎缩的子宫内膜。然而，尽管人们做出了巨大努力来建立基于分子的组织学分类，以下问题仍然必须澄清：是什么触发了肿瘤细胞侵袭子宫肌层，是什么导致了血管或淋巴扩散，最终导致了转移？RUNX1是一种转录因子，最近被确定为侵袭性子宫内膜癌微阵列研究中最高表达的基因之一。另一个候选基因是转录因子ETV5/ERM，它可能与最初的子宫肌层浸润性改变有关。这些研究，以及对其他可能涉及有丝分裂检查点的基因进行的研究，可能有助于理解不同组织类型之间的生物学差异和临床结果。(C)2007爱思唯尔有限公司。保留所有权利。
Endometrial carcinoma (EC) is the most common gynecological malignancy in the western world. A widely accepted dualistic model, which has been established on a morphological basis, differentiates EC into two broad categories: Type I oestrogen-dependent adenocarcinoma with an endometrioid morphology and Type II non-oestrogen-dependent EC with a serous papillary or clear cell morphology.Molecular genetic evidence indicates that endometrial carcinoma, as described in other malignancies, likely develops as the result of a stepwise accumulation of alterations in cellular regulatory pathways, such as oncogene activation and tumor suppressor gene inactivation, which lead to dysfunctional cell growth. These molecular alterations appear to be specific in Type I and Type II cancers.In type I endometrioid endometrial cancer, PTEN gene silencing in conjunction with defects in DNA mismatch repair genes, as evidenced by the microsatellite instability phenotype, or mutations in the K-ras and/or beta-catenin genes, are recognized major alterations, which define the progression of the normal endometrium to hyperplasia, to endometrial intraepithelial neoplasia, and then on to carcinoma. In contrast, Type II cancers show mutations of TP53 and Her-2/neu and seem to arise from a background of atrophic endometrium.Nevertheless, despite the great effort made to establish a molecularly-based histological classification, the following issues must still be clarified: what triggers the tumor cells to invade the myometrium and what causes vascular or lymphatic dissemination, finally culminating in metastasis? RUNX1, a transcription factor, was recently identified as one of the most highly over-expressed genes in a microarray study of invasive endometrial carcinoma. Another candidate gene, which may be associated with an initial switch to myometrial infiltration, is the transcription factor ETV5/ERM. These studies, as well as those conducted for other genes possibly involved in the mitotic checkpoint as a major mechanism of carcinogenesis in non-endometrioid endometrial cancer, could help in understanding the differences in the biology and the clinical outcome among histological types. (c) 2007 Elsevier Ltd. All rights reserved.