Li S F, Shiozawa T, Nakayama K, Nikaido T, Fujii S
Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto, Japan.
Cancer. 1996 Jan 15;77(2):321-9. doi: 10.1002/(SICI)1097-0142(19960115)77:2<321::AID-CNCR15>3.0.CO;2-3.
In the normal cell cycle, the appropriate interaction of factors such as tumor suppressor gene products (retinoblastoma susceptibility [Rb], p53) and cyclins is essential. Abnormalities in the interaction of these factors may result in malignant transformation of the cell. Malignant transformation of the endometrium, which is believed to be a sex steroid-dependent tumor, probably involves a process of uncoupling of these factors and sex steroid hormone receptors. This study is designed to test this hypothesis.
Fifty-six patients whose pathology slides contained either normal or hyperplastic endometrium adjacent to endometrial carcinoma were selected. Immunohistochemical staining of serial paraffin sections was performed using antibodies to estrogen receptors (ER) and progesterone receptors (PR), p53, and Rb, as well as cyclin E.
The normal and hyperplastic endometria adjacent to carcinoma showed positive staining for ER and PR and negative staining for p53. Of 56 carcinomas, 39 (69.6%) showed homogeneous positive staining for ER and PR and negative staining for p53, whereas the remaining 17 carcinomas (30.4%) contained varied distributions of ER- and PR-negative cells, and p53-positive cells (6 were negative or focally positive for ER/PR and diffusely-positive for p53, 4 were regionally-positive for ER/PR and regionally-positive for p53, and 7 were diffusely positive for ER/PR and focally-positive for p53). The p53-positive cells corresponded to those that stained negatively for ER/PR: This topographic inverse relationship between ER/PR expression and p53 expression also correlated with the staining intensities. Furthermore, the cells with weak or negative staining for p53 had a tendency to stain positively for Rb and weakly positive for cyclin E, whereas the cancer cells with definite positivity for p53 tended to stain either weakly or negatively for Rb and definitely positive for cyclin E. The cells showing diffusely positive for p53 were present significantly in clinical Stage III and pathologic Grade G3.
In the development of endometrial carcinoma, stepwise abnormalities of sex steroid receptors, tumor suppressor gene products, and cyclins apparently exist, and may correlate with the progression of the malignant process.
在正常细胞周期中，肿瘤抑制基因产物（视网膜母细胞瘤易感基因[Rb]、p53）和细胞周期蛋白等因子的适当相互作用至关重要。这些因子相互作用的异常可能导致细胞恶性转化。子宫内膜恶性转化被认为是一种依赖性激素的肿瘤，可能涉及这些因子与性激素受体解偶联的过程。本研究旨在验证这一假设。
选择56例病理切片包含与子宫内膜癌相邻的正常或增生期子宫内膜的患者。使用抗雌激素受体（ER）、孕激素受体（PR）、p53和Rb以及细胞周期蛋白E的抗体对连续石蜡切片进行免疫组织化学染色。
癌旁的正常和增生期子宫内膜ER和PR染色阳性，p53染色阴性。56例癌中，39例（69.6%）ER和PR呈均匀阳性染色，p53染色阴性，而其余17例癌（30.4%）含有ER和PR阴性细胞以及p53阳性细胞的不同分布（6例ER/PR阴性或局灶阳性且p53弥漫阳性，4例ER/PR区域阳性且p53区域阳性，7例ER/PR弥漫阳性且p53局灶阳性）。p53阳性细胞与ER/PR染色阴性细胞相对应：ER/PR表达与p53表达之间的这种地形学上的反向关系也与染色强度相关。此外，p53染色弱阳性或阴性的细胞Rb染色倾向于阳性，细胞周期蛋白E弱阳性，而p53明确阳性的癌细胞Rb染色倾向于弱阳性或阴性，细胞周期蛋白E明确阳性。p53弥漫阳性的细胞在临床Ⅲ期和病理G3级中显著存在。
在子宫内膜癌的发生发展过程中，性激素受体、肿瘤抑制基因产物和细胞周期蛋白明显存在逐步异常，且可能与恶性进程的进展相关。
