Endometrial stromal sarcoma expression of estrogen receptors, progesterone receptors and estrogen-induced srp27 (24K) suggests hormone responsiveness

Abstract

The endometrial stroma plays a decisive role in sustaining the gland epithelium along the menstrual cycle, and in preparing the microenvironment that allows embryo implantation. The stroma undergoes important changes during the menstrual cycle that affects both the cell number and differentiation. These changes are regulated by both estrogen and progesterone.Stromal sarcomas are extremely rare, occurring much less than any other uterine tumor. Their origin and biology are poorly understood. The purpose of this work was to try to learn more about the stromal physiology, and also to ascertain whether the stromal sarcoma has characteristics of hormone dependence. We studied the presence of estrogen receptors (ER), progesterone receptors (PR) and the stress-responsive protein of 27K (srp27, a protein first described as an estrogen-induced 24K protein in MCF-7 cells) in both normal stroma and stromal sarcoma. The ER and PR were measured by exchange assays. The srp 27 was studied both by Western-blot and by IHC by means of specific monoclonal antibodies.The stromal sarcomas studied showed a high concentration of both ER (96 to 116 fmol/mg prot.) and PR (565 to 995 fmol/mg prot.). These amounts of ER and PR were higher than the mean found in normal endometrium during the proliferative phase (43 and 637 fmol/mg prot., respectively), and much higher than that of the secretory phase (17 and 229 fmol/mg prot., respectively). The srp27 characterized by Western-blot in both the normal stroma and stromal sarcoma was found to be similar to the srp27 of breast cancer. The IHC results showed a very low expression of srp27 in the stroma during the proliferative phase that increases when the endometrium enters the secretory phase. The low-malignancy grade stromal sarcomas showed abundant expression of srp27, but the high-malignancy grade sarcomas showed no expression of srp27.The obtained results prove the stroma capability to express the srp27. A negative correlation between malignancy of stromal tumors and srp27 expression was found. The presence of ER and PR in some stromal sarcomas proves that they have characteristics of hormone responsiveness. These findings suggest that ER and PR assays should be routinely performed in stromal sarcomas as well as in endometrial adenocarcinomas, and also that antiesterogenic drugs might be considered for the treatment of ER and PR positive stromal sarcomas.