Endometrial glandular dysplasia with frequent p53 gene mutation: A genetic evidence supporting its precancer nature for endometrial serous carcinoma
Endometrial glandular dysplasia with frequent p53 gene mutation: A genetic evidence supporting its precancer nature for endometrial serous carcinoma
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DOI：
10.1158/1078-0432.ccr-07-4837
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发表时间：
2008-04-15
影响因子：
11.5
通讯作者：
Zheng, Wenxin
中科院分区：
文献类型：
--
作者：
Jia, Lin;Liu, Yongjuan;Zheng, Wenxin
目的：子宫内膜腺体发育不良（EmGD）最近被认为是子宫内膜浆液性癌（ESC）的假定前体。本研究的目的是确定 EmGD 是否与 ESC 存在遗传关联，以及是否可用于早期检测。 实验设计：从具有浆液性分化的良性和肿瘤性子宫内膜的系列样本中对抑癌基因 p53 基因进行测序。研究组有 15 个肿瘤子宫，对照组有 12 个年龄匹配的良性子宫。总共获得了 139 个信息样本，其中包括 55 个静息子宫内膜、37 个 EmGD、25 个浆液性子宫内膜上皮内癌 (EIC) 和 22 个 ESC。使用每个子宫的至少一个代表性切片进行p53免疫组织化学染色，以将p53过表达与基因突变状态相关联。结果：在静息子宫内膜、EmGD、浆液性EIC和ESC中分别检测到p53突变的比例为0%、43%、72%和96%。超过 50% 的肿瘤性子宫在 EmGD、浆液性 EIC 和/或 ESC 病变中表现出至少一种相同的 p53 基因突变体。大多数病灶表现为p53蛋白过度表达，与p53基因突变显着相关（P < 0.01）。结论：这一遗传学证据有力地支持EmGD代表ESC或浆液性EIC的癌前病变。 p53基因突变可能是引发子宫内膜浆液性癌变的最重要因素之一。 EmGD 的正确识别将为我们提供早期诊断的机会和控制 ESC 的潜在有效的治疗方式。
Purpose: Endometrial glandular dysplasia (EmGD) has been recently proposed to be a putative precursor to endometrial serous carcinoma (ESC). The purpose of this study is to determine if EmGD is genetically linked to ESC and if it can be used for early detection.Experimental Design: The tumor suppressor p53 gene was sequenced from serial samples of benign and neoplastic endometrial with serous differentiation. The study group contained 15 neoplastic uteri and the control group had 12 age-matched benign uteri. A total of 139 informative samples were obtained, including 55 resting endometrium, 37 EmGD, 25 serous endometrial intraepithelial carcinoma (EIC), and 22 ESC. At least one representative section from each uterus was used for p53 immunohistochemical staining to correlate p53 overexpression with gene mutation status.Results: The mutations of p53 were detected in 0%, 43%, 72%, and 96% in resting endometrium, EmGD, serous EIC, and ESC, respectively. More than 50% of the neoplastic uteri showed at least one identical p53 gene mutant among lesions of EmGD, serous EIC, and/or ESC. The majority of lesions showed overexpression of p53 protein, which was significantly correlated with p53 gene mutation (P < 0.01).Conclusions: This genetic evidence strongly supports that EmGD represents the precancer of ESC or serous EIC. Mutation of p53 gene is probably one of the most important factors to initiate the enclometrial serous carcinogenesis. Correct identification of EmGD will provide us an opportunity of early diagnosis and a potentially effective therapeutic modality to control ESC.