Adult Urology Is There a Role for Serum Human Tissue Kallikrein in Detection of Prostate Cancer? Atsushi Ochiai, Ashish Shukla, John W. Davis, Herbert A. Fritsche, Viju Bhadkamkar, and R. Joseph Babaian OBJECTIVES To retrospectively evaluate the diagnostic performance of a serum human tissue kallikrein 11 (hK11) assay to predict the presence of prostate cancer in a screened population of men with a total prostate-specific antigen (PSA) level between 2.5 and 10.0 ng/mL. METHODS Frozen serum samples from 114 men with a total PSA level between 2.5 and 10.0 ng/mL who had undergone transrectal prostate ultrasound-guided biopsy with at least 10 cores were retrospec- tively analyzed for hK11. The performance characteristics of hK11, PSA, hK11/PSA ratio, and hK11 density (hk11/prostate volume) were analyzed for their ability to differentiate cancer from noncancer. The results obtained were analyzed using the Mann-Whitney U test, chi-square test, and receiver operating characteristic curves. RESULTS Prostate cancer was diagnosed in 36 (32%) of the 114 men whose serum samples were analyzed. No significant differences were found in hK11 (median 0.71 ng/mL versus 0.69 ng/mL), PSA level (median 3.9 ng/mL versus 4.1 ng/mL), hK11/PSA ratio (median 0.15 versus 0.17), or hK11 density (median 0.015 versus 0.016) between men with and without prostate cancer. A com- parison of the areas under the curve for hK11 (0.491), PSA (0.540), hK11/PSA ratio (0.505), and hK11 density (0.589) showed no significant differences. CONCLUSIONS In this retrospective study, hK11, hK11/PSA ratio, and hK11 density showed no diagnostic advantage compared with PSA in differentiating cancer from noncancer in men whose total PSA level was in the range of 2.5 to 10.0 ng/mL. UROLOGY 70: 519 –522, 2007. © 2007 Elsevier Inc. P rostate cancer is the most common cancer in men in North America and is the third leading cause of cancer death. 1 During the early 1990s, an increase occurred in the incidence of prostate cancer detection due to screening for prostate-specific antigen (PSA) and heightened awareness of early detection for this neo- plasm. During the ensuing years, the rate of prostate cancer detection has decreased. Concomitantly, a 6.7% decrease in mortality was documented for this malig- nancy between 1991 and 1995. 2 However, despite the potential impact of PSA testing, the early detection and treatment of this malignancy has been the subject of increasing controversy. 3 Serum PSA is produced almost exclusively by prostatic tissue, but not specifically by prostate cancer tissue. The low specificity of PSA has been a longstanding limitation of the test, such that many efforts to improve specificity have been investigated, including PSA isoforms, ratios of PSA to PSA isoforms, PSA density, and PSA veloci- ty. 4–6 The human kallikrein gene family has recently been expanded to include 15 isoforms. 7 PSA is a member of the kallikrein family and is designated hK3. Another member of this gene family, hK2, has been postulated as an additional marker for prostate cancer. 4 hK11, a trypsin-like serine protease, has been found to be highly expressed in prostate secretions and serum. 7 The earliest discovered source of hK11 was the hip- pocampus in the brain. Subsequently, it has been isolated from other organs, such as the prostate, lung, pancreas, skin, testis, heart, liver, stomach, and salivary glands and from biologic secretions such as breast milk, serum, and seminal plasma. 8 Previously, Nakamura et al. 9 reported a retrospective study of serum banked samples, in which hK11 levels were significantly lower in prostate cancer than in benign prostatic hyperplasia (BPH). To determine linkage of hK11 with prostate cancer as a tumor marker, previous studies have shown that hK11 and the hK11/total PSA ratio were both significantly lower in men with prostate cancer than in men with BPH. 9 In this study, we exam- ined the diagnostic performance of hK11 and its ratio to total PSA to predict the presence of prostate cancer in men from a screening population with a PSA level be- tween 2.5 ng/mL and 10.0 ng/mL. From the Departments of Urology and Laboratory Medicine, University of Texas M.D. Anderson Cancer Center, Houston, Texas Reprint requests: Richard J. Babaian, M.D., Department of Urology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 446, Hous- ton, TX 77030-4009. E-mail: rbabaian@mdanderson.org Submitted: October 23, 2006; accepted (with revisions): April 27, 2007 © 2007 Elsevier Inc. 0090-4295/07/$32.00 519 All Rights Reserved doi:10.1016/j.urology.2007.04.036