The biological significance of sex-steroid metabolism and responsive genes in the endometrium and breast

本研究旨在探讨雌激素和孕激素在子宫内膜和乳腺肿瘤发生中的生物学作用是否不同。特异性孕激素受体(PR)亚型(PRA和PRB)在子宫内膜癌和乳腺癌中作为预测因子的可能作用尚不清楚。本研究旨在探讨子宫内膜样子宫内膜癌和乳腺癌患者肿瘤内PR亚型状态的临床意义。我们发现，PR亚型中的一种或两种都为阴性的病例与患者较短的无病生存期和总生存期显著相关。此外，多变量分析表明，缺乏PRA免疫反应性是患者无病生存的独立危险因素。我们的研究结果表明，PR亚型的表达缺失，尤其是PRA的表达缺失，可能导致子宫内膜样癌的侵袭性生物学特性，在这些患者的预后和/或复发中发挥重要作用。相比之下，PRA富含肿瘤的乳腺癌患者通常被认为与较差的无病生存率有关。这些结果表明PR亚型在子宫内膜癌和乳腺癌中的生物学意义明显不同。此外，对人乳腺和子宫内膜癌细胞的基因芯片分析表明，它们在雌激素和孕激素反应基因的表达上存在很大差异。特别是细胞周期相关基因Cyclin B和CDC在它们之间的表达不同。这些数据表明，雌激素和孕激素在肿瘤发生中的生物学作用在子宫内膜和乳腺中肯定不同，尽管它们都被认为是“雌激素依赖组织”。

This study aims to investigate whether the biological role of estrogen and progestin in tumorigenesis are different between the endometrium and breast. The possible role of specific progesterone receptor (PR) isoforms (PRA and PRB) as predictive factors in endometrial and breast carcinomas is unclear. This study was undertaken to evaluate the clinical significance of intratumoral PR isoforms status in patients with endometrioid endometrial and breast carcinomas. We found that cases that were negative for either one or both of the PR isoforms were significantly associated with shorter disease-free and overall survival of the patients. In addition, multivariate analysis demonstrated that an absence of PRA immunoreactivity was an independent risk factor in disease-free survival of the patients. The results of our study indicate that the loss of expression of PR isoforms, especially expression of PRA, may result in aggressive biological characteristics in human endometrioid endometrial carcinoma that can play important roles in the prognosis and/or recurrence, in these patients. In contrast, breast carcinoma patients with PRA-rich tumors were generally considered to be associated with poorer disease-free survival rates. These results indicate that the biological significance of PR isoforms differ markedly between endometrial and breast carcinomas.In addition, microarray analyses of human breast and endometrial cancer cells revealed that there are large amount of differences between them, regarding estrogen and progestin responsive gene expression.Especially, cell cycle related genes, cyclin B and CDC, expressed differently between them.These data suggest that the biological roles of estrogen and progestin in tumorigenesis are certainly different between the endometrium and breast, although both are considered "estrogen-dependent tissues".