Abstract
Kallikrein 11 (KLK11, TLSP, hippostatin) is a member of the human kallikrein gene family, which includes PSA, KLK2 and 12 other members, all localized on chromosome 19q13.4. The aim of this study was to investigate whether KLK11 expression could be used to discriminate prostate cancer (CaP) from benign prostatic hyperplasia (BPH) in needle prostate biopsies. We analyzed the expression of the prostate-type variant of the KLK11 gene in 64 CaP and BPH tissues obtained by transrectal ultrasound-guided needle biopsy. Reverse transcription (RT), PCR and image analysis methodologies were developed and used. Of the 42 BPH tissues examined, only 10 (23.8%) were positive for prostate-type KLK11 expression, while of the 22 CaP patients, 12 (54.5%) were KLK11-positive (p=0.025). Logistic regression and receiver operating characteristic curve analyses demonstrated that KLK11 expression has a significant discriminatory value (crude odds ratio=3.84, p=0.016; area under the curve, 0.65, 95% CI 0.51–0.80) between CaP and BPH in needle prostate biopsies.
References
Albertsen, P.C., Hanley, J.A., and Fine, J. (2005). 20-year outcomes following conservative management of clinically localized prostate cancer. J. Am. Med. Assoc.293, 2095–2101.10.1001/jama.293.17.2095Search in Google Scholar
Borgono, C.A., Fracchioli, S., Yousef, G.M., Rigault de la Longrais, I.A., Luo, L.Y., Soosaipillai, A., Puopolo, M., Grass, L., Scorilas, A., Diamandis, E.P., and Katsaros, D. (2003). Favorable prognostic value of tissue human kallikrein 11 (hK11) in patients with ovarian carcinoma. Int. J. Cancer106, 605–610.10.1002/ijc.11296Search in Google Scholar
Catalona, W.J., Partin, A.W., Slawin, K.M., Brawer, M.K., Flanigan, R.C., Patel, A., Richie, J.P., deKernion, J.B., Walsh, P.C., Scardino, P.T., et al. (1998). Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial. J. Am. Med. Assoc.279, 1542–1547.10.1001/jama.279.19.1542Search in Google Scholar
Darson, M.F., Pacelli, A., Roche, P., Rittenhouse, H.G., Wolfert, R.L., Young, C.Y., Klee, G.G., Tindall, D.J., and Bostwick, D.G. (1997). Human glandular kallikrein 2 (hK2) expression in prostatic intraepithelial neoplasia and adenocarcinoma: a novel prostate cancer marker. Urology49, 857–862.10.1016/S0090-4295(97)00108-8Search in Google Scholar
Diamandis, E.P., Borgono, C.A., Scorilas, A., Harbeck, N., Dorn, J., and Schmitt, M. (2004). Human kallikrein 11: an indicator of favorable prognosis in ovarian cancer patients. Clin. Biochem.37, 823–829.10.1016/j.clinbiochem.2004.04.009Search in Google Scholar PubMed
Diamandis, E.P., Scorilas, A., Fracchioli, S., Van Gramberen, M., De Bruijn, H., Henrik, A., Soosaipillai, A., Grass, L., Yousef, G.M., Stenman, U.H., et al. (2003). Human kallikrein 6 (hK6): a new potential serum biomarker for diagnosis and prognosis of ovarian carcinoma. J. Clin. Oncol.21, 1035–1043.10.1200/JCO.2003.02.022Search in Google Scholar PubMed
Gregorakis, A.K., Malovrouvas, D., Stefanakis, S., Petraki, K., and Scorilas, A. (2005). Free/total PSA (F/T ratio) kinetics in patients with clinically localized prostate cancer undergoing radical prostatectomy. Clin. Chim. Acta357, 196–201.10.1016/j.cccn.2005.03.027Search in Google Scholar PubMed
Jung, K., Elgeti, U., Lein, M., Brux, B., Sinha, P., Rudolph, B., Hauptmann, S., Schnorr, D., and Loening, S.A. (2000). Ratio of free or complexed prostate-specific antigen (PSA) to total PSA: which ratio improves differentiation between benign prostatic hyperplasia and prostate cancer? Clin. Chem.46, 55–62.10.1093/clinchem/46.1.55Search in Google Scholar
Kozuka, Y., Imai, H., Yamanaka, M., Kozuka, M., Uchida, K., and Shiraishi, T. (2005). Histopathological features of prostate cancer [in Japanese]. Nippon Rinsho63, 231–236.Search in Google Scholar
Magklara, A., Scorilas, A., Catalona, W.J., and Diamandis, E.P. (1999a). The combination of human glandular kallikrein and free prostate-specific antigen (PSA) enhances discrimination between prostate cancer and benign prostatic hyperplasia in patients with moderately increased total PSA. Clin. Chem.45, 1960–1966.10.1093/clinchem/45.11.1960Search in Google Scholar
Magklara, A., Scorilas, A., Lopez-Otin, C., Vizoso, F., Ruibal, A., and Diamandis, E.P. (1999b). Human glandular kallikrein in breast milk, amniotic fluid, and breast cyst fluid. Clin. Chem.45, 1774–1780.10.1093/clinchem/45.10.1774Search in Google Scholar
Magklara, A., Scorilas, A., Stephan, C., Kristiansen, G.O., Hauptmann, S., Jung, K., and Diamandis, E.P. (2000). Decreased concentrations of prostate-specific antigen and human glandular kallikrein 2 in malignant versus nonmalignant prostatic tissue. Urology56, 527–532.10.1016/S0090-4295(00)00621-XSearch in Google Scholar
Nakamura, T., Mitsui, S., Okui, A., Miki, T., and Yamaguchi, N. (2003a). Molecular cloning and expression of a variant form of hippostasin/KLK11 in prostate. Prostate54, 299–305.10.1002/pros.10191Search in Google Scholar
Nakamura, T., Scorilas, A., Stephan, C., Jung, K., Soosaipillai, A.R., and Diamandis, E.P. (2003b). The usefulness of serum human kallikrein 11 for discriminating between prostate cancer and benign prostatic hyperplasia. Cancer Res.63, 6543–6546.Search in Google Scholar
Nakamura, T., Stephan, C., Scorilas, A., Yousef, G.M., Jung, K., and Diamandis, E.P. (2003c). Quantitative analysis of hippo-stasin/KLK11 gene expression in cancerous and noncancerous prostatic tissues. Urology61, 1042–1046.10.1016/S0090-4295(02)02443-3Search in Google Scholar
Nam, R.K., Diamandis, E.P., Toi, A., Trachtenberg, J., Magklara, A., Scorilas, A., Papnastasiou, P.A., Jewett, M.A., and Narod, S.A. (2000). Serum human glandular kallikrein-2 protease levels predict the presence of prostate cancer among men with elevated prostate-specific antigen. J. Clin. Oncol.18, 1036–1042.10.1200/JCO.2000.18.5.1036Search in Google Scholar
Obiezu, C.V., Giltay, E.J., Magklara, A., Scorilas, A., Gooren, L., Yu, H., and Diamandis, E.P. (2000a). Dramatic suppression of plasma and urinary prostate specific antigen and human glandular kallikrein by antiandrogens in male-to-female transsexuals. J. Urol.163, 802–805.10.1016/S0022-5347(05)67808-1Search in Google Scholar
Obiezu, C.V., Giltay, E.J., Magklara, A., Scorilas, A., Gooren, L.J., Yu, H., Howarth, D.J., and Diamandis, E.P. (2000b). Serum and urinary prostate-specific antigen and urinary human glandular kallikrein concentrations are significantly increased after testosterone administration in female-to-male transsexuals. Clin. Chem.46, 859–862.10.1093/clinchem/46.6.859Search in Google Scholar
Oesterling, J.E., Jacobsen, S.J., and Cooner, W.H. (1995). The use of age-specific reference ranges for serum prostate specific antigen in men 60 years old or older. J. Urol.153, 1160–1163.10.1097/00005392-199504000-00025Search in Google Scholar
Scorilas, A., Borgono, C.A., Harbeck, N., Dorn, J., Schmalfeldt, B., Schmitt, M., and Diamandis, E.P. (2004). Human kallikrein 13 protein in ovarian cancer cytosols: a new favorable prognostic marker. J. Clin. Oncol.22, 678–685.10.1200/JCO.2004.05.144Search in Google Scholar PubMed
Srigley, J.R. (2004). Benign mimickers of prostatic adenocarcinoma. Mod. Pathol.17, 328–348.10.1038/modpathol.3800055Search in Google Scholar PubMed
Stavropoulou, P., Gregorakis, A.K., Plebani, M., and Scorilas, A. (2005). Expression analysis and prognostic significance of human kallikrein 11 in prostate cancer. Clin. Chim. Acta357, 190–195.10.1016/j.cccn.2005.03.026Search in Google Scholar PubMed
Stenman, U.H., Leinonen, J., Zhang, W.M., and Finne, P. (1999). Prostate-specific antigen. Semin. Cancer Biol.9, 83–93.10.1006/scbi.1998.0086Search in Google Scholar
Yoshida, S., Taniguchi, M., Suemoto, T., Oka, T., He, X., and Shiosaka, S. (1998). cDNA cloning and expression of a novel serine protease, TLSP. Biochim. Biophys. Acta1399, 225–228.10.1016/S0167-4781(98)00116-XSearch in Google Scholar
Yousef, G.M., Chang, A., Scorilas, A., and Diamandis, E.P. (2000a). Genomic organization of the human kallikrein gene family on chromosome 19q13.3–q13.4. Biochem. Biophys. Res. Commun.276, 125–133.10.1006/bbrc.2000.3448Search in Google Scholar
Yousef, G.M., Scorilas, A., and Diamandis, E.P. (2000b). Genomic organization, mapping, tissue expression, and hormonal regulation of trypsin-like serine protease (TLSP PRSS20), a new member of the human kallikrein gene family. Genomics63, 88–96.10.1006/geno.1999.6072Search in Google Scholar
Yousef, G.M., Scorilas, A., Magklara, A., Soosaipillai, A., and Diamandis, E.P. (2000c). The KLK7 (PRSS6) gene, encoding for the stratum corneum chymotryptic enzyme is a new member of the human kallikrein gene family – genomic characterization, mapping, tissue expression and hormonal regulation. Gene254, 119–128.10.1016/S0378-1119(00)00280-8Search in Google Scholar
Yousef, G.M., Scorilas, A., Jung, K., Ashworth, L.K., and Diamandis, E.P. (2001). Molecular cloning of the human kallikrein 15 gene (KLK15). Up-regulation in prostate cancer. J. Biol. Chem.276, 53–61.10.1074/jbc.M005432200Search in Google Scholar
Yousef, G.M., Borgono, C.A., Scorilas, A., Ponzone, R., Biglia, N., Iskander, L., Polymeris, M.E., Roagna, R., Sismondi, P., and Diamandis, E.P. (2002a). Quantitative analysis of human kallikrein gene 14 expression in breast tumours indicates association with poor prognosis. Br. J. Cancer87, 1287–1293.10.1038/sj.bjc.6600623Search in Google Scholar
Yousef, G.M., Obiezu, C.V., Jung, K., Stephan, C., Scorilas, A., and Diamandis, E.P. (2002b). Differential expression of kallikrein gene 5 in cancerous and normal testicular tissues. Urology60, 714–718.10.1016/S0090-4295(02)01811-3Search in Google Scholar
Yousef, G.M., Scorilas, A., Magklara, A., Memari, N., Ponzone, R., Sismondi, P., Biglia, N., Abd Ellatif, M., and Diamandis, E.P. (2002c). The androgen-regulated gene human kallikrein 15 (KLK15) is an independent and favourable prognostic marker for breast cancer. Br. J. Cancer87, 1294–1300.10.1038/sj.bjc.6600590Search in Google Scholar PubMed PubMed Central
Yousef, G.M., Scorilas, A., Nakamura, T., Ellatif, M.A., Ponzone, R., Biglia, N., Maggiorotto, F., Roagna, R., Sismondi, P., and Diamandis, E.P. (2003). The prognostic value of the human kallikrein gene 9 (KLK9) in breast cancer. Breast Cancer Res. Treat.78, 149–158.10.1023/A:1022931403825Search in Google Scholar
Yousef, G.M., Obiezu, C.V., Luo, L.Y., Magklara, A., Borgono, C.A., Kishi, T., Memari, N., Michael, P., Sidiropoulos, M., Kurlender, L., et al. (2005). Human tissue kallikreins: from gene structure to function and clinical applications. Adv. Clin. Chem.39, 11–79.10.1016/S0065-2423(04)39002-5Search in Google Scholar
Zhu, H., Roehl, K.A., Antenor, J.A., and Catalona, W.J. (2005). Biopsy of men with PSA level of 2.6 to 4.0 ng/ml associated with favorable pathologic features and PSA progression rate: a preliminary analysis. Urology66, 547–551.Search in Google Scholar
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