The effect of progestin on factors influencing growth and invasion of endometrial carcinoma.

Progesterone (P) and progestins play an important role in the control of endometrial growth. We have investigated P and progestin effects on endometrial estrogen extraction, on basement membrane (BM) synthesis and on the presence of the epidermal growth factor receptor (EGFr) in normal and pathologic endometrium. E2 uptake, evaluated in human isolated perfused uteri is significantly decreased by P. BMs investigated using immunohistochemistry, with antisera to collagen IV and laminin, were found around stromal cells only in the luteal phase or during P or progestin administration. Glandular BM, discontinuous in hyperplastic and carcinomatous endometria, were restored to integrity only in typical hyperplasia after therapy with progestin. Endometrial EGFr is modified by P: revelation of this antigen is increased in proliferative phase and decreased in secretory phase. Similarly this molecule was present in hyperplastic and carcinomatous endometria. Only in benign hyperplasia did we observe no staining for the same antigen after progestinic therapy. These data suggest that P or progestins may also have an indirect influence through mechanisms such as estrogen uptake and tissue factor activity with important differences between normal and pathologic endometrium.