-Original-

Determining Best Potential Predictor during High-dose Progestin Therapy for Early Staged and Well-differentiated Endometrial Adenocarcinoma Using Semiquantitative Analysis Based on Image Processing and Immunohistochemistry

Seiryu Kamoi¹, Yoshiharu Ohaki², Osamu Mori², Takashi Yamada¹, Masaharu Fukunaga³ and Toshiyuki Takeshita¹

¹Division of Reproductive Medicine, Perinatology and Gynecologic Oncology, Graduate School of Medicine, Nippon Medical School
²Department of Surgical Pathology, Nippon Medical School Chiba Hokusoh Hospital
³Department of Pathology, The Jikei University Daisan Hospital, Tokyo

This study aimed to examine whether morphological changes during the early stage of treatment or indices of proliferation, apoptosis, or hormone receptors are reliable predictors of the hormonal response to uterus-preserving high-dose progestin therapy in patients with endometrial adenocarcinoma. Seven patients (5 good responders and 2 poor responders) with presumptive stage IA endometrial adenocarcinoma treated with 600 mg/day of medroxyprogesterone acetate were reviewed. Epithelial cell size and stromal area observable on microscopic examination of hematoxylin and eosin-stained sections, and immunostaining labeling indices for Ki-67 nuclear antigen, single-stranded DNA, estrogen receptor, and progesterone receptor were semiquantitatively analyzed before treatment and after 4, 8, 12, and 16 weeks of treatment using computer imaging programs. The mean ratio of cell size after 4 weeks of treatment to that before treatment in good responders was 3.83, whereas the ratios in the 2 poor responders were 1.08 and 0.98. The mean Ki-67 nuclear antigen labeling index before treatment was 37.2% for the 5 good responders but was 51.0% in the 2 poor responders. The indices of the poor responders remained high (20%-77%), even after 16 weeks of treatment; in contrast, the indices of the good responders were low (0.4%-7.3%) throughout the treatment period. No definitive differences in labeling indices for single-stranded DNA, estrogen receptor, or progesterone receptor were observed between good and poor responders or at different stages of treatment (p>0.05). In conclusion, a higher epithelial cell size ratio after 4 weeks of treatment in conjunction with lower Ki-67 nuclear antigen labeling indices could be a potential predictor of hormonal response.

J Nippon Med Sch 2011; 78: 84-95

Keywords
high-dose progestin therapy, immunohistochemistry, medroxyprogesterone acetate, semiquantitative analysis, uterine preservation

Correspondence to
Seiryu Kamoi, MD, Department of Obstetrics and Gynecology, Nippon Medical School Hospital, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
skamoi@nms.ac.jp

Received, February 12, 2010
Accepted, December 14, 2010