High expression of steroid sulfatase mRNA predicts poor prognosis in patients with estrogen receptor-positive breast cancer.
OBJECTIVE
Prognostic significance of the intratumoral mRNA expression of three enzymes related to in situ estrogen biosynthesis, i.e., aromatase, sulfatase, and 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1), was evaluated in patients with invasive breast cancer.


METHODS
Aromatase, sulfatase, and 17beta-HSD1 mRNA levels in tumor tissues (n = 181) and normal breast tissues (n = 34) were examined by a quantitative, real-time PCR assay and compared with various clinicopathological factors as well as prognosis.


RESULTS
The sulfatase mRNA levels, but not the aromataseor 17beta-HSD1 mRNA levels, were significantly associated with lymph node metastases (P < 0.005), histological grade III (P < 0.001), and poor prognosis (P < 0.005). The association between the sulfatase mRNA and poor prognosis was found to be significant (P < 0.001) only in patients with estrogen receptor (ER)-positive tumors but not in ER negative tumors. In ER-positive tumors, the sulfatase mRNA levels was a significant prognostic factor independent of the lymph node status and histological grade by multivariate analysis.


CONCLUSIONS
The sulfatase mRNA levels can serve as a significant, independent prognostic factor only in ER-positive tumors. It is speculated that the up-regulation of sulfatase mRNA levels leads to a high intratumoral estrogen concentration and, thus, an enhanced stimulation of tumor growth through ERs.
Miyoshi
Yasuo
Y
Department of Surgical Oncology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Ando
Akiko
A
Hasegawa
Seiichi
S
Ishitobi
Makoto
M
Taguchi
Tetsuya
T
Tamaki
Yasuhiro
Y
Noguchi
Shinzaburo
S
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics; D001141:Aromatase / Q000235:genetics; D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015999:Multivariate Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis*; D043266:Steryl-Sulfatase / Q000235:genetics*
D012333:RNA, Messenger; D011960:Receptors, Estrogen; D015067:17-Hydroxysteroid Dehydrogenases; D001141:Aromatase; D043266:Steryl-Sulfatase