High expression of steroid sulfatase mRNA predicts poor prognosis in patients with estrogen receptor-positive breast cancer

Purpose: Prognostic significance of the intratumoral mRNA expression of three enzymes related to in situ estrogen biosynthesis, i.e., aromalase, sulfalase, and 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1), was evaluated in patients with invasive breast cancer. Experimental Design: Aromalase, 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 aromatase or 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.