Comparison of human prostate specific glandular kallikrein 2 and prostate specific antigen gene expression in prostate with gene amplification and overexpression of prostate specific glandular kallikrein 2 in tumor tissue.

Abstract

There is a need for specific markers that can indicate the different stages of prostate carcinoma. There is ongoing speculation concerning the value of prostate specific glandular kallikrein (hK2) in this regard. The expression levels of both hK2 and human prostate specific antigen (hPSA) were compared at the mRNA and protein levels by using in situ hybridization and immunohistochemistry techniques in tissue specimens from patients with benign prostatic hyperplasia and malignant prostate carcinoma. The respective gene copy numbers were analyzed by a competitively differential polymerase chain reaction-based method. In situ hybridization revealed that hK2 was expressed at significantly higher levels in malignant prostate tissue compared with benign prostate tissue (P < 0.0005), whereas hPSA expression levels were the reverse (P = 0.06). In benign tissue, the mean level of hK2 mRNA was 82% of the respective value of hPSA (P < 0.003), whereas, in tumor tissue, the mean hK2 expression level was 21% higher than that of hPSA (P < 0.01). The results at the protein level supported the mRNA findings: hPSA expression was lower in malignant tissues compared with benign tissues (17 of 20 specimens), whereas an increase in hK2 expression was detected in 17 of 19 specimens. The authors report that the hK2 gene (hKLK2) was amplified in prostate carcinoma tissue, whereas the hPSA gene was not. There was a correlation between hPSA and hK2 mRNA levels in both benign tissue (correlation coefficient [r] = 0.735; P < 0.01) and malignant tissue (r = 0.767; P < 0.01). Gene amplification of hKLK2 may be one of the factors leading to higher expression of hK2 in prostate carcinoma. The correlation between hK2 and hPSA expression levels indicates coordinated expression of the genes in both normal and abnormal prostate gland. The results suggest the potential value of hK2 in the diagnosis of prostate carcinoma through mRNA analyses and gene amplification.