Lax S F, Pizer E S, Ronnett B M, Kurman R J
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Hum Pathol. 1998 Jun;29(6):551-8. doi: 10.1016/s0046-8177(98)80002-6.
This study was designed to analyze certain clinicopathological features and the profile of p53, Ki-67, estrogen (ER), and progesterone (PR) receptor expression of clear cell carcinoma of the endometrium and to determine whether the pathogenesis of clear cell carcinoma can be accommodated by a dualistic model of endometrial carcinogenesis. In this model, endometrioid carcinoma develops from endometrial hyperplasia under unopposed estrogenic stimulation, and serous carcinoma develops in atrophic endometrium from a putative precursor lesion designated endometrial intraepithelial carcinoma (EIC). Twenty-one clear cell carcinomas of the endometrium were analyzed and compared with 77 endometrioid carcinomas of all grades and 30 serous carcinomas. Clear cell carcinomas showed a distinctive immunoprofile characterized by immunonegativity for ER and PR, low immunoreactivity for p53, and a high Ki-67 proliferation index. ER, PR, and Ki-67 expression were similar to serous carcinoma, but p53 expression was significantly lower in clear cell carcinoma (P < .05). ER and PR expression were significantly lower, and the Ki-67 proliferation index was significantly higher in clear cell carcinoma compared with endometrioid carcinomas (P < .05). p53 expression tended to be higher in clear cell carcinoma compared with endometrioid carcinoma, but the difference was not statistically significant. In contrast to endometrioid carcinoma, clear cell carcinoma was rarely associated with endometrial hyperplasia and serous carcinoma was not. Subdividing clear cell carcinoma morphologically into one that resembled serous carcinoma (clear cell carcinoma with serous features) and another that did not (typical clear cell carcinoma) showed that clear cell carcinoma with serous features had a higher Ki-67 proliferation index than typical clear cell carcinoma, although expression of ER, PR, and p53 were similar. Clear cell carcinoma with serous features was associated with EIC in 50% and was not associated with endometrial hyperplasia. In contrast, typical clear cell carcinoma was associated with endometrial hyperplasia in 40% and was not associated with EIC. In summary, this study provides evidence that clear cell carcinoma of the endometrium, like serous carcinoma, is estrogen independent and shows a high Ki-67 proliferation index. In contrast to serous carcinoma, strong p53 expression occurred less frequently in clear cell carcinoma and predominantly in clear cell carcinoma with serous features. The findings suggest that the molecular events that underlie the development of clear cell carcinoma differ from those of endometrioid and serous carcinoma.
本研究旨在分析子宫内膜透明细胞癌的某些临床病理特征以及p53、Ki-67、雌激素（ER）和孕激素（PR）受体的表达情况，以确定子宫内膜癌发生的二元模型是否能解释透明细胞癌的发病机制。在该模型中，子宫内膜样癌在无对抗性雌激素刺激下由子宫内膜增生发展而来，浆液性癌则在萎缩的子宫内膜中由一种假定的前体病变即子宫内膜上皮内癌（EIC）发展而来。对21例子宫内膜透明细胞癌进行了分析，并与77例各级别的子宫内膜样癌和30例浆液性癌进行了比较。透明细胞癌显示出独特的免疫表型，其特征为ER和PR免疫阴性、p53免疫反应性低以及Ki-67增殖指数高。ER、PR和Ki-67的表达与浆液性癌相似，但透明细胞癌中p53的表达明显较低（P <.05）。与子宫内膜样癌相比，透明细胞癌中ER和PR的表达明显较低，而Ki-67增殖指数明显较高（P <.05）。与子宫内膜样癌相比，透明细胞癌中p53的表达倾向于更高，但差异无统计学意义。与子宫内膜样癌不同，透明细胞癌很少与子宫内膜增生相关，浆液性癌则不然。将透明细胞癌在形态上细分为类似浆液性癌的一种（具有浆液性特征的透明细胞癌）和另一种不类似的（典型透明细胞癌），结果显示，具有浆液性特征的透明细胞癌的Ki-67增殖指数高于典型透明细胞癌，尽管ER、PR和p53的表达相似。具有浆液性特征的透明细胞癌有50%与EIC相关，且与子宫内膜增生无关。相比之下，典型透明细胞癌有40%与子宫内膜增生相关，且与EIC无关。总之，本研究提供了证据表明，子宫内膜透明细胞癌与浆液性癌一样，不依赖雌激素且显示出高Ki-67增殖指数。与浆液性癌不同，透明细胞癌中p53的强表达较少见，且主要见于具有浆液性特征的透明细胞癌。这些发现表明，透明细胞癌发生的分子事件不同于子宫内膜样癌和浆液性癌。
