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

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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".