Steroid sulfatase and estrogen sulfotransferase in human endometrial carcinoma.
OBJECTIVE
Intratumoral metabolism and synthesis of estrogens are considered to play important roles in the pathogenesis and/or development of human endometrial carcinoma. Steroid sulfatase hydrolyzes biologically inactive estrogen sulfates to active estrogens, whereas estrogen sulfotransferase sulfonates estrogens to estrogen sulfates. However, the status of steroid sulfatase and/or estrogen sulfotransferase in human endometrial carcinoma has not been examined.


METHODS
We first examined the expression of steroid sulfatase and estrogen sulfotransferase in 6 normal endometrium and 76 endometrial carcinoma using immunohistochemistry to elucidate the possible involvement of steroid sulfatase and estrogen sulfotransferase. We then evaluated the enzymatic activity and the semiquantitative analysis of mRNA using reverse transcription-PCR in 21 endometrial carcinomas. We correlated these findings with various clinicopathological parameters including the expression of aromatase, 17beta-hydroxysteroid dehydrogenase type 1 and type 2.


RESULTS
Steroid sulfatase and estrogen sulfotransferase immunoreactivity was detected in 65 of 76 (86%) and 22 of 76 (29%) cases, respectively. Results of immunoreactivity for steroid sulfatase and estrogen sulfotransferase were significantly correlated with those of enzymatic activity and semiquantitative analysis of mRNA. No significant correlations were detected among the expression of the enzymes involved in intratumoral estrogen metabolism. There was a significant correlation between steroid sulfatase/estrogen sulfotransferase ratio and clinical outcomes of the patients. However, there were no significant differences between steroid sulfatase or estrogen sulfotransferase and estrogen receptor, progesterone receptor, Ki67, histologic grade, or clinical outcomes of the patients.


CONCLUSIONS
Results of our study demonstrated that increased steroid sulfatase and decreased estrogen sulfotransferase expression in human endometrial carcinomas may result in increased availability of biologically active estrogens and may be related to estrogen-dependent biological features of carcinoma.
Utsunomiya
Hiroki
H
Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Japan. u-kichi@pg8.so-net.ne.jp
Ito
Kiyoshi
K
Suzuki
Takashi
T
Kitamura
Takako
T
Kaneko
Chika
C
Nakata
Taisuke
T
Niikura
Hitoshi
H
Okamura
Kunihiro
K
Yaegashi
Nobuo
N
Sasano
Hironobu
H
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D018269:Carcinoma, Endometrioid / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004717:Endometrium / Q000201:enzymology* / Q000473:pathology; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D011960:Receptors, Estrogen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D043266:Steryl-Sulfatase / Q000235:genetics / Q000378:metabolism*; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*
D004967:Estrogens; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D001141:Aromatase; D015238:Sulfotransferases; C020122:estrone sulfotransferase; D043266:Steryl-Sulfatase