Increased expression of anterior gradient-2 is significantly associated with poor survival of prostate cancer patients

Abstract

Anterior gradient-2 (AGR2) expression was examined in a series of prostate cell lines and in an archival set of prostate tissues. The relative levels of AGR2 expression in the malignant cell lines PC-3 and PC-3M were, respectively, 5.3+/-0.1 and 3.8+/-0.2 times that detected in the benign cell line PNT-2. Immunohistochemical staining in 106 cases showed that amongst seven normal cases, one (14.3%) was unstained, five (71.4%) stained weakly positive and one (14.3%) stained moderately positive. Amongst 34 benign prostate hyperplastic (BPH) cases, 12 (35.3%) were unstained, 18 (52.9%) stained weakly positive and four (11.8%) stained moderately positive. Amongst 65 carcinomas, three (4.6%) were unstained, 14 (21.5%) stained weakly positive, 19 (29.2%) stained moderately positive and 29 (44.9%) stained strongly positive. AGR2 expression in carcinomas was significantly higher than that in BPH (chi(2)-test, P<0.001). Kaplan-Meier survival analysis showed that increased AGR2 expression was significantly (log rank test, P=0.007) associated with reduced patient-survival time. Increased joint Gleason score (GS) was significantly (log rank test, P=0.001) associated with poor patient survival. However, neither prostate specific antigen (PSA) level, nor androgen receptor (AR) index, was significantly associated with patient-survival time. Increased AGR2 expression was significantly correlated with high GS (two-sided Fisher's exact test, P<0.001) and PSA levels (Mann-Whitney U-test, P=0.047), but not significantly related to the level of AR (Mann-Whitney U-test, P=0.286). These results suggest that increased AGR2 expression is a valuable prognostic factor to predict the clinical outcome of the prostate cancer patients.