Abnormal expression of 17 beta-hydroxysteroid dehydrogenases in breast cancer predicts late recurrence

The 17 beta -hydroxysteroid dehydrogenase (17 beta -HSD) enzymes are involv ed in the interconversion of biologically active and inactive sex steroids and are considered to play a critical role in the in situ metabolism of est rogen, especially in estrogen-dependent breast cancer. The gene encoding 17 beta -HSD type 2 is located at 16q24.1-2, and earlier studies have shown t hat allelic loss in this region is an early and frequent event in breast ca ncer progression. Recurrence of hormone-dependent breast cancer frequently occurs several years after the primary treatment. The aim of this study was to investigate whether the expression of 17 beta -HSD types 1 and 2 differ s in tumors from patients with late relapses (>5 years) compared with contr ols without recurrence after long-term follow-up. Using realtime reverse tr anscription-PCR, we found that the normal mammary gland expressed both 17 b eta -HSD types 1 and 2, whereas the tumors frequently lacked detectable lev els of type 2. Only 10% of the estrogen receptor-positive tumors expressed type 2, whereas 31% of the ER-negative tumors did so (P = 0.031). In a case -control series of 84 patients, a high level of 17 beta -HSD type 1 indicat ed increased risk to develop late relapse of breast cancer (odds ratio. 3.0 ; 95% confidence interval, 1.0-12.6; P = 0.041), whereas retained expressio n of type 2 indicated decreased risk (odds ratio, 0.25; 95% confidence inte rval, 0.05-1.2; P = 0.050). In multivariate analysis of the estrogen recept or-positive patients, the absence of 17 beta -HSD type 2 combined with a hi gh expression of type 1 showed prognostic significance (P = 0.016) in addit ion to DNA aneuploidy (P = 0.0058), whereas progesterone receptor status di d not (P = 0.71). These findings suggest that abnormal expression of 17 bet a -HSD isoforms has prognostic significance in breast cancer and that alter ed expression of these enzymes may have importance in breast cancer progres sion.