Apoptosis May Be an Early Event of Progestin Therapy for Endometrial Hyperplasia

doi:10.1006/gyno.2000.5955

Gynecologic Oncology

Volume 79, Issue 2, November 2000, Pages 169-176

https://doi.org/10.1006/gyno.2000.5955 Get rights and content

Abstract

Objective. The aim of this study was to investigate the role of apoptosis during progestin therapy for the treatment of endometrial hyperplasia.

Methods. Pre- and posttreatment paraffin-embedded endometrial tissue samples from 19 women with endometrial hyperplasia were examined for changes in glandular cellularity and apoptotic activity related to the administration of progestins. Twelve patients were successfully treated with progestin therapy and 7 patients failed treatment. Glandular cellularity was assessed based on calculating the average number of cells per gland obtained on histologic examination of hematoxylin and eosin stained tissue sections. Apoptotic activity was assessed on the same tissue sections by counting the average number of apoptotic cells per 10 high power fields (hpf) using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay. The effects of progesterone on apoptotic activity in a low-grade endometrial adenocarcinoma cell line (Ishikawa cells) was also examined using an ELISA cell death detection kit.

Results. Glandular cellularity significantly decreased with progestin therapy in both treatment outcome groups. The reduction in cells per gland was significantly greater in the group of successfully treated cases compared to the treatment failures (P = 0.005). However, within the successfully treated group, in situ detection of apoptotic cells using the TUNEL assay showed no statistical difference between pre- and posttreatment endometrial samples. Interestingly, a significant decrease in apoptosis was found in posttreatment samples of the group with persistent hyperplasia. The average number of apoptotic cells detected in 10 hpf was reduced from 7.9 prior to treatment to 3.1 after progestin therapy (P = 0.03). In the progesterone-treated Ishikawa cell line, an increase in apoptotic activity started at 24 h, reached a peak at 48 h, and continued up to 72 h of hormone treatment. At 48 h, apoptotic activity was 42.6% greater than in the untreated control (P = 0.04). By 72 h of progesterone treatment, apoptosis was 37.2% greater in the treated cells compared to the noninoculated cells (P = 0.04).

Conclusions. Progestin-induced apoptosis may occur during the early period of treatment for endometrial hyperplasia. Compared to the fully responsive group, persistent endometrial hyperplasia may have intrinsically different molecular mechanisms in response to progestin therapy.

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¹: To whom reprint requests should be addressed at Department of Pathology, Yale University School of Medicine, East Pavilion Room 2-607, 20 York Street, P.O. Box 208070, New Haven, CT 06520-8070. E-mail: [email protected].

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Regular ArticleApoptosis May Be an Early Event of Progestin Therapy for Endometrial Hyperplasia

Abstract

Gynecol Oncol

Am J Obstet Gynecol

Obstet Gynecol

Blood

Gynecol Oncol

Gynecol Oncol

Cancer Lett

J Steroid Biochem Mol Biol

Gynecol Oncol

J Steroid Biochem Mol Biol

Long-term effect of megestrol acetate in the treatment of endometrial hyperplasia

Am J Obstet Gynecol

Progestin alone as primary treatment of endometrial carcinoma in premenopausal women

Cancer

The effects of progestational agents on hyperplasia and carcinoma in situ of the endometrium

Int J Gynaecol Obstet

Effects of hormone therapy on the endometrium

Mod Pathol

Female sex steroid receptors in normal, hyperplastic and carcinomatous endometrium. The relationship to serum steroid hormones and gonadotropins and changes during medroxyprogesterone acetate administration

Int J Cancer

Effects of estrogens and progestins on the biochemistry and morphology of the postmenopausal endometrium

N Engl J Med

Apoptosis: molecular mechanism for physiologic cell death

Clin Lab Sci

Regular Article
Apoptosis May Be an Early Event of Progestin Therapy for Endometrial Hyperplasia