High-Level Glyoxalase 1 (GLO1) expression is linked to poor prognosis in prostate cancer.

Abstract

Glyoxalase 1 (GLO1) is an enzyme involved in removal of toxic byproducts accumulating during glycolysis from the cell. GLO1 is up regulated in many cancer types but its role in prostate cancer is largely unknown. Here, we employed GLO1 immunohistochemistry on a tissue microarray including 11 152 tumors and an attached clinical and molecular database. Normal prostate epithelium was negative for GLO1, whereas 2059 (27.3%) of 7552 interpretable cancers showed cytoplasmic GLO1 staining, which was considered weak in 8.8%, moderate in 12.5%, and strong in 6.1% of tumors. Up regulation of GLO1 was significantly linked to high original Gleason grade, advanced pathological tumor stage and positive lymph node status (P < 0.0001 each). Comparison of GLO1 staining with several common genomic alterations of prostate cancers revealed a strong link between GLO1 up regulation and TMPRSS2:ERG fusion (P < 0.0001) and an ERG-independent association with PTEN deletion (P < 0.0001). GLO1 up regulation was strongly linked to early biochemical recurrence in univariate analysis (P < 0.0001) and predicted poor prognosis independent from most (except from nodal stage) established prognostic parameters in multivariate analysis (P ≤ 0.03). GLO1 upregulation is linked to aggressive prostate cancers characterized by ERG fusion and PTEN deletion. The strong and independent prognostic value makes it a promising candidate for routine diagnostic applications either alone or in combination with other markers.