Progestin effects on epidermal growth factor receptor (EGFR) endometrial expression in normal and hyperplastic endometrium

The epidermal growth factor (EGF) and its receptor (EGFR) are involved in the control of the human endometrial growth [1]. The EGFR endometrial expression is up-regulated by estrogens [2]. The endometrial EGFR increases during the follicular phase and decreases in the luteal phase indicating an inhibiting effect of progesterone [3]. In the present study the effects of estrogens and progestins on the EGFR endometrial immunohistochemical expression was investigated. Forty-five women were recruited. Twenty women had all been in postmenopause. The postmenopausal women were treated with transdermal 17 β-estradiol, 50 γ/24 h. for 20 days, associated to oral micronized progesterone, 300 mg/day, the last 13 days of treatment. Endometrial samples were collected during the third cycles of treatment, after 9–10 days of 17 β-estradiol and after at least 9–10 days of treatment with progesterone. The samples of 25 typical endometrial hyperplasia were also selected. All these women were treated for at least 20 days with Danazol, 400 mg/day and then resubmitted to endometrial biopsy. EGFR expression was investigated as elsewhere descripted [4]. The estimation of EGFR positivity was semiquantitative and based on immunostaining density and distribution. The histological features and the EGFR immunostaining before and after treatments are reported in Tables 1 and 2. The EGFR endometrial expression was found present during the administration of 17 β-estradiol alone. During the administration of both 17 β-estradiol and progesterone the EGFR immunostaining was present even less marked in comparison to the proliferative phase (Table 1). Concerning the cases of endometrial typical hyperplasia treated with Danazol, 15 specimens were found atrophic, seven showed an arrested proliferative epithelium and three featured a pseudodecidual stromal pattern. In all but four specimens with a weak EGFR positivity, the EGFR immunostaining was completely inhibited. In the present study the EGFR immunostaining was absent in the atrophic endometrium but positive when the proliferative estrogens action appeared. During the progesterone administration the proliferative features changed to secretive pattern. The EGFR immunostaining was present but slightly reduced if compared to the proliferative endometrium. Danazol is a synthetic steroid that is able to induce atrophy of endometrium through a progestin-like action. When Danazol was administered to subjects with endometrial hyperplasia and an atrophic endometrium was observed, the EGFR immunostaining resulted negative. However if the estrogens stimulation was not completely inhibited, a weak positivity of EGFR was present. Therefore the progestins action on EGFR endometrial expression appears related to the progestins suppressive effects on estrogens endometrial stimulation.