Ambros R A, Vigna P A, Figge J, Kallakury B V, Mastrangelo A, Eastman A Y, Malfetano J, Figge H L, Ross J S
Department of Pathology, Albany Medical College, NY 12208.
Cancer. 1994 Mar 15;73(6):1686-92. doi: 10.1002/1097-0142(19940315)73:6<1686::aid-cncr2820730622>3.0.co;2-w.
Genetic changes in the development of endometrial carcinoma have not been characterized, and little is known of tumor or metastatic suppressor gene status in these malignancies. The current study on endometrioid carcinoma was undertaken to examine the status of two tumor suppressor genes that frequently have been found to be altered in human malignancies (the p53 gene and the retinoblastoma [Rb] gene) and to examine the status of the candidate metastatic suppressor gene, nm23-H1.
The status of the p53 gene was studied by immunohistochemistry of formalin-fixed paraffin-embedded biopsy samples from 72 patients with atypical endometrial hyperplasia or endometrioid carcinoma who underwent hysterectomy immediately after biopsy and from 5 patients with benign endometria. A search for loss of heterozygosity (LOH) of the nm23 gene after DNA extraction from frozen tissues and hybridization with nm23-H1 cDNA specific probe was made in 10 endometrial carcinomas. Rb gene status was evaluated by image analysis quantification of immunoreactive retinoblastoma protein in frozen sections of 10 carcinomas and 2 benign endometria.
p53 expression was low in all benign endometria, but high expression was found in 2 (15%) of 13 atypical hyperplasias and in 23 (39%) of 59 carcinomas. High levels of p53 expression in endometrioid carcinoma correlated with the spread of disease outside of the uterus and by logistic regression, the presence of squamous differentiation, nuclear grade, and high p53 expression in the biopsy all independently correlated with spread of disease outside of the uterus. Although 7 of the 10 carcinomas studied were informative, LOH for the nm23 gene was not seen in any, including a site of metastasis. Rb protein expression in endometrial carcinoma was similar to expression in benign endometria.
Although this study found no evidence of nm23-H1 gene alteration or alterations in Rb protein levels in endometrial carcinoma, high expression of p53 protein was sporadically identified in biopsy specimens of atypical hyperplasia and frequently found in endometrioid carcinomas. Determination of p53 expression in combination with the presence or absence of squamous differentiation and nuclear grade in biopsy material may help predict spread of endometrioid carcinoma outside the uterus and facilitate therapeutic planning before hysterectomy.
子宫内膜癌发生发展过程中的基因改变尚未明确，对于这些恶性肿瘤中的肿瘤或转移抑制基因状态也知之甚少。本项关于子宫内膜样癌的研究旨在检测两种在人类恶性肿瘤中常发生改变的抑癌基因（p53基因和视网膜母细胞瘤[Rb]基因）的状态，并检测候选转移抑制基因nm23-H1的状态。
通过免疫组织化学方法研究p53基因状态，所用标本为72例非典型子宫内膜增生或子宫内膜样癌患者活检后立即行子宫切除获取的福尔马林固定石蜡包埋活检样本，以及5例良性子宫内膜患者的样本。从10例子宫内膜癌的冷冻组织中提取DNA，与nm23-H1 cDNA特异性探针杂交，检测nm23基因的杂合性缺失（LOH）。通过图像分析定量检测10例癌组织和2例良性子宫内膜冷冻切片中免疫反应性视网膜母细胞瘤蛋白，评估Rb基因状态。
所有良性子宫内膜中p53表达均较低，但在13例非典型增生中有2例（15%）、59例癌中有23例（39%）呈高表达。子宫内膜样癌中p53高表达与疾病子宫外播散相关，经逻辑回归分析，活检中鳞状分化的存在、核分级以及p53高表达均与疾病子宫外播散独立相关。虽然所研究的10例癌中有7例信息充分，但未发现任何一例存在nm23基因的杂合性缺失，包括转移部位。子宫内膜癌中Rb蛋白表达与良性子宫内膜中的表达相似。
虽然本研究未发现子宫内膜癌中存在nm23-H1基因改变或Rb蛋白水平改变的证据，但在非典型增生活检标本中偶见p53蛋白高表达，且在子宫内膜样癌中常见。结合活检材料中鳞状分化的有无及核分级测定p53表达，可能有助于预测子宫内膜样癌的子宫外播散，并有助于在子宫切除术前制定治疗方案。
