Reduced KLK2 expression is a strong and independent predictor of poor prognosis in ERG‐negative prostate cancer

Background Kallikrein‐related peptidase 2 (KLK2)—like KLK3 (prostate‐specific antigen [PSA])—belongs to the highly conserved serine proteases of the glandular kallikrein protein family (KLK family). Studies suggested that measurement of KLK2 serum levels advanced the predictive accuracy of PSA testing in prostate cancer. Methods To clarify the potential utility of KLK2 as a prognostic tissue biomarker, KLK2 expression was analyzed by immunohistochemistry in more than 12 000 prostate cancers. Results Normal epithelium cells usually showed weak to moderate KLK2 immunostaining, whereas KLK2 was negative in 23%, weak in 38%, moderate in 35%, and strong in 4% of 9576 analyzable cancers. Lost or reduced KLK2 immunostaining was associated with advanced tumor stage, high Gleason score, lymph node metastasis, increased cell proliferation, positive resection margin, and early PSA recurrence (P