The correlation between the response to progestogen treatment and the expression of progesterone receptor B and 17beta-hydroxysteroid dehydrogenase type 2 in human endometrial carcinoma.
OBJECTIVE
In situ metabolism and synthesis of oestrogens are considered to play important roles in the pathogenesis and development of human endometrial endometrioid adenocarcinoma. Approximately 3-5% of patients with these neoplasms are under age 40, some of whom have been treated with progestogen alone as a primary therapy for both atypical endometrial hyperplasia and adenocarcinoma in order to preserve their fertility. Medroxyprogesterone acetate (MPA) has been used extensively in the treatment of both breast and endometrial disorders as an endocrine therapy. However, details of the alterations of in situ oestrogen metabolism following progestogen treatment have yet to be fully elucidated.


METHODS
In this study we examined the immunolocalization of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) types 1 and 2, oestrogen receptor (ER), progesterone receptor (PR)A + PRB, PRB, and Ki67 in progestogen-treated endometrial endometrioid adenocarcinoma (16 cases). We compared our findings both prior to and following treatment. These findings were then correlated with the treatment outcome of individual patients in order to elucidate factors associated with the response to treatment.


RESULTS
17beta-HSD type 2 immunoreactivity was detected in 8/16 cases examined, whereas 17beta-HSD type 1 immunoreactivity was undetected in all cases examined. 17beta-HSD type 2 positive immunostaining, PRA + PRB labelling index (LI), and PRB/PRA + PRB ratio were all significantly higher in cases responding to the treatment than in those not responding. There were no significant correlations between responsive and nonresponsive cases for positive 17beta-HSD type 1 immunostaining, Ki67 LI, ER LI and age. There were no significant differences in the positive immunostaining for 17beta-HSD types 1 and 2, Ki67 LI, ER LI, PRA + PRB LI, age and PRB/PRA + PRB ratio between specimens taken prior to and following progestogen treatment.


CONCLUSIONS
These results suggest that in situ abundance of 17beta-HSD type 2 and PR, especially PRB, can predict the possible response of patients with endometrial carcinoma to progestogen treatment.
Utsunomiya
Hiroki
H
Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Japan. H-Utsu@ob-gy.med.tohoku.ac.jp
Suzuki
Takashi
T
Ito
Kiyoshi
K
Moriya
Takuya
T
Konno
Ryo
R
Sato
Shinji
S
Yaegashi
Nobuo
N
Okamura
Kunihiro
K
Sasano
Hironobu
H
D015067:17-Hydroxysteroid Dehydrogenases / Q000032:analysis*; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004960:Estradiol Dehydrogenases; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000032:analysis; D008525:Medroxyprogesterone / Q000627:therapeutic use*; D045167:Progesterone Congeners / Q000627:therapeutic use*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis*; D016896:Treatment Outcome
D015415:Biomarkers; D019394:Ki-67 Antigen; D045167:Progesterone Congeners; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C101118:progesterone receptor A; C097314:progesterone receptor B; D015067:17-Hydroxysteroid Dehydrogenases; D004960:Estradiol Dehydrogenases; C523763:HSD17B2 protein, human; D008525:Medroxyprogesterone