**8. References**


Biomarkers of Aggressiveness in Prostate Cancer 13

Duffy, M.J. (2004). The urokinase plasminogen activator system: role in malignancy. Curr

Eeles, R.A.; Kote-Jarai, Z.; Giles, G.G.; Olama, A.A.; Guy, M.; Jugurnauth, S.K.; Mulholland,

Fine, S.W.; Gopalan, A.; Leversha, M.A.; Al-Ahmadie, H.A.; Tickoo, S.K.; Zhou, Q.;

Fredolini, C.; Liotta, L.A.& Petricoin, E.F. (2010). Application of proteomic technologies

Gavrilov, D.; Kenzior, O.; Evans, M.; Calaluce, R.& Folk, W.R. (2001). Expression of

Getzenberg, R.H.; Pienta, K.J.; Huang, E.Y.& Coffey, D.S. (1991). Identification of nuclear

Girvan, A.R.; Chang, P.; van Huizen, I.; Moussa, M.; Xuan, J.W.; Stitt, L.; Chin, J.L.;

Gopalan, A.; Leversha, M.A.; Satagopan, J.M.; Zhou, Q.; Al-Ahmadie, H.A.; Fine, S.W.;

Groskopf, J.; Aubin, S.M.; Deras, I.L.; Blase, A.; Bodrug, S.; Clark, C.; Brentano, S.; Mathis, J.;

Gu, Z.; Thomas, G.; Yamashiro, J.; Shintaku, I.P.; Dorey, F.; Raitano, A.; Witte, O.N.; Said,

cancer. *Oncogene*, Vol.19, No.10, (Mar 2), pp.1288-1296, ISSN 0950-9232

Satagopan, J.M.; Scardino, P.T.; Gerald, W.L.& Reuter, V.E. (2010). TMPRSS2-ERG gene fusion is associated with low Gleason scores and not with high-grade morphological features. *Mod Pathol*, Vol.23, No.10, (Oct), pp.1325-1333, ISSN

for prostate cancer detection, prognosis, and tailored therapy. *Crit Rev Clin Lab Sci*,

urokinase plasminogen activator and receptor in conjunction with the ets family and AP-1 complex transcription factors in high grade prostate cancers. *Eur J Cancer*,

matrix proteins in the cancer and normal rat prostate. *Cancer Res*, Vol.51, No.24,

Yamasaki, Y.& Izawa, J.I. (2005). Increased intratumoral expression of prostate secretory protein of 94 amino acids predicts for worse disease recurrence and progression after radical prostatectomy in patients with prostate cancer. *Urology*,

Eastham, J.A.; Scardino, P.T.; Scher, H.I.; Tickoo, S.K.; Reuter, V.E.& Gerald, W.L. (2009). TMPRSS2-ERG gene fusion is not associated with outcome in patients treated by prostatectomy. *Cancer Res*, Vol.69, No.4, (Feb 15), pp.1400-1406, ISSN

Pham, J.; Meyer, T.; Cass, M.; Hodge, P.; Macairan, M.L.; Marks, L.S.& Rittenhouse, H. (2006). APTIMA PCA3 molecular urine test: development of a method to aid in the diagnosis of prostate cancer. *Clin Chem*, Vol.52, No.6, (Jun), pp.1089-1095, ISSN

J.W.; Loda, M.& Reiter, R.E. (2000). Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate

S.; Leongamornlert, D.A.; Edwards, S.M.; Morrison, J.; Field, H.I.; Southey, M.C.; Severi, G.; Donovan, J.L.; Hamdy, F.C.; Dearnaley, D.P.; Muir, K.R.; Smith, C.; Bagnato, M.; Ardern-Jones, A.T.; Hall, A.L.; O'Brien, L.T.; Gehr-Swain, B.N.; Wilkinson, R.A.; Cox, A.; Lewis, S.; Brown, P.M.; Jhavar, S.G.; Tymrakiewicz, M.; Lophatananon, A.; Bryant, S.L.; Horwich, A.; Huddart, R.A.; Khoo, V.S.; Parker, C.C.; Woodhouse, C.J.; Thompson, A.; Christmas, T.; Ogden, C.; Fisher, C.; Jamieson, C.; Cooper, C.S.; English, D.R.; Hopper, J.L.; Neal, D.E.& Easton, D.F. (2008). Multiple newly identified loci associated with prostate cancer susceptibility.

Pharm Des, Vol.10, No.1, pp.39-49, ISSN 1381-6128

Nat Genet, Vol.40, No.3, (Mar), pp.316-321, ISSN 1546-1718

Vol.47, No.3, (May-Jun), pp.125-138, ISSN 1040-8363

Vol.37, No.8, (May), pp.1033-1040, ISSN 0959-8049

Vol.65, No.4, (Apr), pp.719-723, ISSN 1527-9995

(Dec 15), pp.6514-6520, ISSN 0008-5472

1530-0285

1538-7445

0009-9147

identifies fatal human prostate cancer. Oncogene, Vol.27, No.3, (Jan 10), pp.253-263, ISSN 1476-5594


Barry, M.; Dhillon, P.K.; Stampfer, M.J.; Perner, S.; Ma, J.; Giovannucci, E.; Kurth, T.; Mucci,

Bastian, P.J.; Palapattu, G.S.; Lin, X.; Yegnasubramanian, S.; Mangold, L.A.; Trock, B.;

Berg, A.; Berner, A.; Lilleby, W.; Bruland, O.S.; Fossa, S.D.; Nesland, J.M.& Kvalheim, G.

Bjartell, A.S.; Al-Ahmadie, H.; Serio, A.M.; Eastham, J.A.; Eggener, S.E.; Fine, S.W.; Udby, L.;

Bussemakers, M.J.; van Bokhoven, A.; Verhaegh, G.W.; Smit, F.P.; Karthaus, H.F.; Schalken,

Cozzi, P.J.; Wang, J.; Delprado, W.; Madigan, M.C.; Fairy, S.; Russell, P.J.& Li, Y. (2006).

de Kok, J.B.; Verhaegh, G.W.; Roelofs, R.W.; Hessels, D.; Kiemeney, L.A.; Aalders, T.W.;

Demichelis, F.; Fall, K.; Perner, S.; Andren, O.; Schmidt, F.; Setlur, S.R.; Hoshida, Y.;

ISSN 1476-5594

Study. Prostate, (Jun 28), ISSN 1097-0045

Vol.120, No.8, (Apr 15), pp.1603-1609, ISSN 0020-7136

pp.4037-4043, ISSN 1078-0432

pp.4130-4138, ISSN 1078-0432

pp.5975-5979, ISSN 0008-5472

15), pp.433-447, ISSN 0730-2312

pp.3880-3883, ISSN 0008-5472

0046-8177

ISSN 0008-5472

identifies fatal human prostate cancer. Oncogene, Vol.27, No.3, (Jan 10), pp.253-263,

L.A.& Rubin, M.A. (2011). alpha-Methylacyl-CoA racemase expression and lethal prostate cancer in the Physicians' Health Study and Health Professionals Follow-up

Eisenberger, M.A.; Partin, A.W.& Nelson, W.G. (2005). Preoperative serum DNA GSTP1 CpG island hypermethylation and the risk of early prostate-specific antigen recurrence following radical prostatectomy. Clin Cancer Res, Vol.11, No.11, (Jun 1),

(2007). Impact of disseminated tumor cells in bone marrow at diagnosis in patients with nonmetastatic prostate cancer treated by definitive radiotherapy. Int J Cancer,

Gerald, W.L.; Vickers, A.J.; Lilja, H.; Reuter, V.E.& Scardino, P.T. (2007). Association of cysteine-rich secretory protein 3 and beta-microseminoprotein with outcome after radical prostatectomy. Clin Cancer Res, Vol.13, No.14, (Jul 15),

J.A.; Debruyne, F.M.; Ru, N.& Isaacs, W.B. (1999). DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res, Vol.59, No.23, (Dec 1),

Evaluation of urokinase plasminogen activator and its receptor in different grades of human prostate cancer. Hum Pathol, Vol.37, No.11, (Nov), pp.1442-1451, ISSN

Swinkels, D.W.& Schalken, J.A. (2002). DD3(PCA3), a very sensitive and specific marker to detect prostate tumors. Cancer Res, Vol.62, No.9, (May 1), pp.2695-2698,

Mosquera, J.M.; Pawitan, Y.; Lee, C.; Adami, H.O.; Mucci, L.A.; Kantoff, P.W.; Andersson, S.O.; Chinnaiyan, A.M.; Johansson, J.E.& Rubin, M.A. (2007). TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort. Oncogene, Vol.26, No.31, (Jul 5), pp.4596-4599, ISSN 0950-9232 Dhir, R.; Vietmeier, B.; Arlotti, J.; Acquafondata, M.; Landsittel, D.; Masterson, R.&

Getzenberg, R.H. (2004). Early identification of individuals with prostate cancer in

associated with aggressive prostate cancers. Cancer Res, Vol.60, No.14, (Jul 15),

negative biopsies. J Urol, Vol.171, No.4, (Apr), pp.1419-1423, ISSN 0022-5347 Dong, J.T. (2006). Prevalent mutations in prostate cancer. J Cell Biochem, Vol.97, No.3, (Feb

Dong, J.T.; Chen, C.; Stultz, B.G.; Isaacs, J.T.& Frierson, H.F., Jr. (2000). Deletion at 13q21 is


Biomarkers of Aggressiveness in Prostate Cancer 15

Joung, J.Y.; Cho, K.S.; Kim, J.E.; Seo, H.K.; Chung, J.; Park, W.S.; Choi, M.K.& Lee, K.H.

Kibel, A.S.; Faith, D.A.; Bova, G.S.& Isaacs, W.B. (2000). Loss of heterozygosity at 12P12-13

Kollermann, J.; Weikert, S.; Schostak, M.; Kempkensteffen, C.; Kleinschmidt, K.; Rau, T.&

Kuefer, R.; Varambally, S.; Zhou, M.; Lucas, P.C.; Loeffler, M.; Wolter, H.; Mattfeldt, T.;

Kumar-Sinha, C.; Tomlins, S.A.& Chinnaiyan, A.M. (2008). Recurrent gene fusions in prostate cancer. *Nat Rev Cancer*, Vol.8, No.7, (Jul), pp.497-511, ISSN 1474-1768 Lakshmanan, Y.; Subong, E.N.& Partin, A.W. (1998). Differential nuclear matrix protein

Lam, J.S.; Yamashiro, J.; Shintaku, I.P.; Vessella, R.L.; Jenkins, R.B.; Horvath, S.; Said, J.W.&

Leinonen, K.A.; Tolonen, T.T.; Bracken, H.; Stenman, U.H.; Tammela, T.L.; Saramaki, O.R.&

Leman, E.S.; Cannon, G.W.; Trock, B.J.; Sokoll, L.J.; Chan, D.W.; Mangold, L.; Partin, A.W.&

Lilja, H.& Abrahamsson, P.A. (1988). Three predominant proteins secreted by the human

Lu, T.& Hano, H. (2008). Deletion at chromosome arms 6q16-22 and 10q22.3-23.1 associated

Luo, J.; Zha, S.; Gage, W.R.; Dunn, T.A.; Hicks, J.L.; Bennett, C.J.; Ewing, C.M.; Platz, E.A.;

cancer. *Urology*, Vol.69, No.4, (Apr), pp.714-720, ISSN 1527-9995

prostate gland. *Prostate*, Vol.12, No.1, pp.29-38, ISSN 0270-4137

*Clin Oncol*, Vol.26, No.30, (Oct 20), pp.4928-4933, ISSN 1527-7755

*Urol*, Vol.58, No.1, (Jul), pp.12-18; discussion 20-11, ISSN 1873-7560

Vol.101, No.2, (Feb 1), pp.145-148, ISSN 1096-9098

pp.192-196, ISSN 0022-5347

ISSN 0027-8424

361, ISSN 1476-5608

No.3, (Sep), pp.841-848, ISSN 0002-9440

No.4, (Apr), pp.1354-1358, 0022-5347 (Print)

(May 15), pp.2845-2851, ISSN 1078-0432

marker in prostate cancer detection and identification of aggressive tumours. *Eur* 

(2010). Prostate stem cell antigen mRNA in peripheral blood as a potential predictor of biochemical recurrence in high-risk prostate cancer. *J Surg Onco*l,

in primary and metastatic prostate adenocarcinoma. *J Urol*, Vol.164, No.1, (Jul),

Pantel, K. (2008). Prognostic significance of disseminated tumor cells in the bone marrow of prostate cancer patients treated with neoadjuvant hormone treatment. *J* 

Hautmann, R.E.; Gschwend, J.E.; Barrette, T.R.; Dunn, R.L.; Chinnaiyan, A.M.& Rubin, M.A. (2002). alpha-Methylacyl-CoA racemase: expression levels of this novel cancer biomarker depend on tumor differentiation. *Am J Pathol*, Vol.161,

expression in prostate cancers: correlation with pathologic stage. J Urol, Vol.159,

Reiter, R.E. (2005). Prostate stem cell antigen is overexpressed in prostate cancer metastases. Clin Cancer Res, Vol.11, No.7, (Apr 1), pp.2591-2596, 1078-0432 (Print) Lee, W.H.; Morton, R.A.; Epstein, J.I.; Brooks, J.D.; Campbell, P.A.; Bova, G.S.; Hsieh, W.S.;

Isaacs, W.B.& Nelson, W.G. (1994). Cytidine methylation of regulatory sequences near the pi-class glutathione S-transferase gene accompanies human prostatic carcinogenesis. *Proc Natl Acad Sci U S A*, Vol.91, No.24, (Nov 22), pp.11733-11737,

Visakorpi, T. (2010). Association of SPINK1 expression and TMPRSS2:ERG fusion with prognosis in endocrine-treated prostate cancer. *Clin Cancer Res*, Vol.16, No.10,

Getzenberg, R.H. (2007). EPCA-2: a highly specific serum marker for prostate

with initiation of prostate cancer. *Prostate Cancer Prostatic Dis*, Vol.11, No.4, pp.357-

Ferdinandusse, S.; Wanders, R.J.; Trent, J.M.; Isaacs, W.B.& De Marzo, A.M. (2002).


Gupta, A.; Lotan, Y.; Ashfaq, R.; Roehrborn, C.G.; Raj, G.V.; Aragaki, C.C.; Montorsi, F.&

Haese, A.; de la Taille, A.; van Poppel, H.; Marberger, M.; Stenzl, A.; Mulders, P.F.; Huland,

Han, K.R.; Seligson, D.B.; Liu, X.; Horvath, S.; Shintaku, P.I.; Thomas, G.V.; Said, J.W.&

Hara, N.; Kasahara, T.; Kawasaki, T.; Bilim, V.; Obara, K.; Takahashi, K.& Tomita, Y. (2002).

Hayes, J.D.& Strange, R.C. (1995). Potential contribution of the glutathione S-transferase

Heneghan, H.M.; Miller, N.& Kerin, M.J. (2010). MiRNAs as biomarkers and therapeutic

Hessels, D.; Smit, F.P.; Verhaegh, G.W.; Witjes, J.A.; Cornel, E.B.& Schalken, J.A. (2007).

Hessels, D.; van Gils, M.P.; van Hooij, O.; Jannink, S.A.; Witjes, J.A.; Verhaegh, G.W.&

Hienert, G.; Kirchheimer, J.C.; Christ, G.; Pfluger, H.& Binder, B.R. (1988a). Plasma

Hienert, G.; Kirchheimer, J.C.; Pfluger, H.& Binder, B.R. (1988b). Urokinase-type

Jentzmik, F.; Stephan, C.; Lein, M.; Miller, K.; Kamlage, B.; Bethan, B.; Kristiansen, G.& Jung,

Jentzmik, F.; Stephan, C.; Miller, K.; Schrader, M.; Erbersdobler, A.; Kristiansen, G.; Lein,

carcinoma. *Eur Urol*, Vol.15, No.3-4, pp.256-258, ISSN 0302-2838

No.5, (May), pp.1124-1133, ISSN 1873-7560

Vol.171, No.3, (Mar), pp.1117-1121, ISSN 0022-5347

*Res*, Vol.8, No.6, (Jun), pp.1794-1799, ISSN 1078-0432

Vol.13, No.17, (Sep 1), pp.5103-5108, ISSN 1078-0432

(Mar), pp.193-207, ISSN 1071-5762

pp.10-16, ISSN 1097-0045

pp.1388-1413, ISSN 1093-4715

(Feb), pp.706-711, ISSN 1527-3792

0302-2838

4973

Shariat, S.F. (2009). Predictive value of the differential expression of the urokinase plasminogen activation axis in radical prostatectomy patients. *Eur Urol*, Vol.55,

H.; Abbou, C.C.; Remzi, M.; Tinzl, M.; Feyerabend, S.; Stillebroer, A.B.; van Gils, M.P.& Schalken, J.A. (2008). Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy. *Eur Urol*, Vol.54, No.5, (Nov), pp.1081-1088, ISSN

Reiter, R.E. (2004). Prostate stem cell antigen expression is associated with gleason score, seminal vesicle invasion and capsular invasion in prostate cancer. *J Urol*,

Reverse transcription-polymerase chain reaction detection of prostate-specific antigen, prostate-specific membrane antigen, and prostate stem cell antigen in one milliliter of peripheral blood: value for the staging of prostate cancer. *Clin Cancer* 

supergene family to resistance to oxidative stress. *Free Radic Res*, Vol.22, No.3,

targets in cancer. *Curr Opin Pharmacol*, Vol.10, No.5, (Oct), pp.543-550, ISSN 1471-

Detection of TMPRSS2-ERG fusion transcripts and prostate cancer antigen 3 in urinary sediments may improve diagnosis of prostate cancer. *Clin Cancer Res*,

Schalken, J.A. (2010). Predictive value of PCA3 in urinary sediments in determining clinico-pathological characteristics of prostate cancer. *Prostate*, Vol.70, No.1, (Jan 1),

urokinase-type plasminogen activator correlates to bone scintigraphy in prostatic

plasminogen activator as a marker for the formation of distant metastases in prostatic carcinomas. *J Urol*, Vol.140, No.6, (Dec), pp.1466-1469, ISSN 0022-5347 Hsing, A.W.& Chokkalingam, A.P. (2006). Prostate cancer epidemiology. *Front Biosci*, Vol.11,

K. (2011). Sarcosine in prostate cancer tissue is not a differential metabolite for prostate cancer aggressiveness and biochemical progression. *J Urol*, Vol.185, No.2,

M.& Jung, K. (2010). Sarcosine in urine after digital rectal examination fails as a

marker in prostate cancer detection and identification of aggressive tumours. *Eur Urol*, Vol.58, No.1, (Jul), pp.12-18; discussion 20-11, ISSN 1873-7560


Biomarkers of Aggressiveness in Prostate Cancer 17

Pulukuri, S.M.; Estes, N.; Patel, J.& Rao, J.S. (2007). Demethylation-linked activation of

Reeves, J.R.; Dulude, H.; Panchal, C.; Daigneault, L.& Ramnani, D.M. (2006). Prognostic

Reeves, J.R.; Xuan, J.W.; Arfanis, K.; Morin, C.; Garde, S.V.; Ruiz, M.T.; Wisniewski, J.;

Rhodes, D.R.; Barrette, T.R.; Rubin, M.A.; Ghosh, D.& Chinnaiyan, A.M. (2002). Meta-

Rice, K.R.; Chen, Y.; Ali, A.; Whitman, E.J.; Blase, A.; Ibrahim, M.; Elsamanoudi, S.; Brassell,

Rogers, C.G.; Yan, G.; Zha, S.; Gonzalgo, M.L.; Isaacs, W.B.; Luo, J.; De Marzo, A.M.; Nelson,

Roupret, M.; Hupertan, V.; Catto, J.W.; Yates, D.R.; Rehman, I.; Proctor, L.M.; Phillips, J.;

Rubin, M.A.; Bismar, T.A.; Andren, O.; Mucci, L.; Kim, R.; Shen, R.; Ghosh, D.; Wei, J.T.;

Rubin, M.A.; Zerkowski, M.P.; Camp, R.L.; Kuefer, R.; Hofer, M.D.; Chinnaiyan, A.M.&

*Cancer Res*, Vol.67, No.3, (Feb 1), pp.930-939, ISSN 0008-5472

*S A*, Vol.95, No.4, (Feb 17), pp.1735-1740, ISSN 0027-8424

ISSN 1078-0432

pp.4427-4433, ISSN 0008-5472

1503, ISSN 0022-5347

1055-9965

No.5, (Mar 1), pp.1572-1576, ISSN 1078-0432

No.4, (Feb 15), pp.952-956, ISSN 1097-0215

urokinase plasminogen activator is involved in progression of prostate cancer.

value of prostate secretory protein of 94 amino acids and its binding protein after radical prostatectomy. *Clin Cancer Res*, Vol.12, No.20 Pt 1, (Oct 15), pp.6018-6022,

Panchal, C.& Tanner, J.E. (2005). Identification, purification and characterization of a novel human blood protein with binding affinity for prostate secretory protein of 94 amino acids. *Biochem J*, Vol.385, No.Pt 1, (Jan 1), pp.105-114, ISSN 1470-8728 Reiter, R.E.; Gu, Z.; Watabe, T.; Thomas, G.; Szigeti, K.; Davis, E.; Wahl, M.; Nisitani, S.;

Yamashiro, J.; Le Beau, M.M.; Loda, M.& Witte, O.N. (1998). Prostate stem cell antigen: a cell surface marker overexpressed in prostate cancer. *Proc Natl Acad Sci U* 

analysis of microarrays: interstudy validation of gene expression profiles reveals pathway dysregulation in prostate cancer. *Cancer Res*, Vol.62, No.15, (Aug 1),

S.; Furusato, B.; Stingle, N.; Sesterhenn, I.A.; Petrovics, G.; Miick, S.; Rittenhouse, H.; Groskopf, J.; McLeod, D.G.& Srivastava, S. (2010). Evaluation of the ETS-related gene mRNA in urine for the detection of prostate cancer. *Clin Cancer Res*, Vol.16,

W.G.& Pavlovich, C.P. (2004). Prostate cancer detection on urinalysis for alpha methylacyl coenzyme a racemase protein. *J Urol*, Vol.172, No.4 Pt 1, (Oct), pp.1501-

Meuth, M.; Cussenot, O.& Hamdy, F.C. (2008). Promoter hypermethylation in circulating blood cells identifies prostate cancer progression. *Int J Cance*r, Vol.122,

Chinnaiyan, A.M.; Adami, H.O.; Kantoff, P.W.& Johansson, J.E. (2005). Decreased alpha-methylacyl CoA racemase expression in localized prostate cancer is associated with an increased rate of biochemical recurrence and cancer-specific death. *Cancer Epidemiol Biomarkers Prev*, Vol.14, No.6, (Jun), pp.1424-1432, ISSN

Rimm, D.L. (2004). Quantitative determination of expression of the prostate cancer protein alpha-methylacyl-CoA racemase using automated quantitative analysis (AQUA): a novel paradigm for automated and continuous biomarker measurements. *Am J Pathol*, Vol.164, No.3, (Mar), pp.831-840, ISSN 0002-9440 Rubin, M.A.; Zhou, M.; Dhanasekaran, S.M.; Varambally, S.; Barrette, T.R.; Sanda, M.G.;

Pienta, K.J.; Ghosh, D.& Chinnaiyan, A.M. (2002). alpha-Methylacyl coenzyme A

Alpha-methylacyl-CoA racemase: a new molecular marker for prostate cancer. *Cancer Res*, Vol.62, No.8, (Apr 15), pp.2220-2226, ISSN 0008-5472


Matsuyama, H.; Oba, K.; Matsuda, K.; Yoshihiro, S.; Tsukamoto, M.; Kinjo, M.; Sagiyama, K.;

Matsuyama, H.; Pan, Y.; Oba, K.; Yoshihiro, S.; Matsuda, K.; Hagarth, L.; Kudren, D.; Naito,

Mehra, R.; Tomlins, S.A.; Shen, R.; Nadeem, O.; Wang, L.; Wei, J.T.; Pienta, K.J.; Ghosh, D.;

Mitchell, P.S.; Parkin, R.K.; Kroh, E.M.; Fritz, B.R.; Wyman, S.K.; Pogosova-Agadjanyan,

Miyake, H.; Hara, I.; Yamanaka, K.; Gohji, K.; Arakawa, S.& Kamidono, S. (1999). Elevation

Nakanishi, H.; Groskopf, J.; Fritsche, H.A.; Bhadkamkar, V.; Blase, A.; Kumar, S.V.; Davis,

Nam, R.K.; Reeves, J.R.; Toi, A.; Dulude, H.; Trachtenberg, J.; Emami, M.; Daigneault, L.;

Nam, R.K.; Sugar, L.; Yang, W.; Srivastava, S.; Klotz, L.H.; Yang, L.Y.; Stanimirovic, A.;

Paul, B.; Dhir, R.; Landsittel, D.; Hitchens, M.R.& Getzenberg, R.H. (2005). Detection of

Peng, X.; Guo, W.; Liu, T.; Wang, X.; Tu, X.; Xiong, D.; Chen, S.; Lai, Y.; Du, H.; Chen, G.;

Regulation of EMT. *PLoS One*, Vol.6, No.5, pp.e20341, ISSN 1932-6203

*Res*, Vol.65, No.10, (May 15), pp.4097-4100, ISSN 0008-5472

*Cancer Res*, Vol.62, No.8, (Apr 15), pp.2220-2226, ISSN 0008-5472

*Cancer Res*, Vol.7, No.10, (Oct), pp.3139-3143, ISSN 1078-0432

*Mod Pathol*, Vol.20, No.5, (May), pp.538-544, ISSN 0893-3952

*Prostate*, Vol.39, No.2, (May), pp.123-129, ISSN 0270-4137

Vol.174, No.1, (Apr 1), pp.24-34, ISSN 0165-4608

(Jul 29), pp.10513-10518, ISSN 1091-6490

discussion 1809-1810, ISSN 1527-3792

(Apr), pp.1291-1297, ISSN 0022-5347

1695, ISSN 0007-0920

Alpha-methylacyl-CoA racemase: a new molecular marker for prostate cancer.

Takei, M.; Yamaguchi, A.; Sasaki, K.& Naito, K. (2007). Haploinsufficiency of 8p22 may influence cancer-specific survival in prostate cancer. *Cancer Genet Cytogenet*,

K.; Bergerheim, U.S.& Ekman, P. (2001). Deletions on chromosome 8p22 may predict disease progression as well as pathological staging in prostate cancer. *Clin* 

Rubin, M.A.; Chinnaiyan, A.M.& Shah, R.B. (2007). Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer.

E.L.; Peterson, A.; Noteboom, J.; O'Briant, K.C.; Allen, A.; Lin, D.W.; Urban, N.; Drescher, C.W.; Knudsen, B.S.; Stirewalt, D.L.; Gentleman, R.; Vessella, R.L.; Nelson, P.S.; Martin, D.B.& Tewari, M. (2008). Circulating microRNAs as stable blood-based markers for cancer detection. *Proc Natl Acad Sci U S A*, Vol.105, No.30,

of serum levels of urokinase-type plasminogen activator and its receptor is associated with disease progression and prognosis in patients with prostate cancer.

J.W.; Troncoso, P.; Rittenhouse, H.& Babaian, R.J. (2008). PCA3 molecular urine assay correlates with prostate cancer tumor volume: implication in selecting candidates for active surveillance. *J Urol*, Vol.179, No.5, (May), pp.1804-1809;

Panchal, C.; Sugar, L.; Jewett, M.A.& Narod, S.A. (2006). A novel serum marker, total prostate secretory protein of 94 amino acids, improves prostate cancer detection and helps identify high grade cancers at diagnosis. *J Urol*, Vol.175, No.4,

Encioiu, E.; Neill, M.; Loblaw, D.A.; Trachtenberg, J.; Narod, S.A.& Seth, A. (2007). Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer. *Br J Cancer*, Vol.97, No.12, (Dec 17), pp.1690-

prostate cancer with a blood-based assay for early prostate cancer antigen. *Cancer* 

Liu, G.; Tang, Y.; Huang, S.& Zou, X. (2011). Identification of miRs-143 and -145 that Is Associated with Bone Metastasis of Prostate Cancer and Involved in the


Biomarkers of Aggressiveness in Prostate Cancer 19

Thuret, R.; Chantrel-Groussard, K.; Azzouzi, A.R.; Villette, J.M.; Guimard, S.; Teillac, P.;

Tong, A.W.; Fulgham, P.; Jay, C.; Chen, P.; Khalil, I.; Liu, S.; Senzer, N.; Eklund, A.C.; Han,

Uetsuki, H.; Tsunemori, H.; Taoka, R.; Haba, R.; Ishikawa, M.& Kakehi, Y. (2005).

*Cancer Gene Ther*, Vol.16, No.3, (Mar), pp.206-216, ISSN 1476-5500

cancer. *Br J Cancer*, Vol.92, No.2, (Jan 31), pp.236-240, ISSN 0007-0920 Tomlins, S.A.; Rhodes, D.R.; Perner, S.; Dhanasekaran, S.M.; Mehra, R.; Sun, X.W.;

(Oct 28), pp.644-648, ISSN 1095-9203

1078-0432

1699, ISSN 1095-9203

D.J.& Chanock, S.J. (2008). Multiple loci identified in a genome-wide association study of prostate cancer. *Nat Genet*, Vol.40, No.3, (Mar), pp.310-315, ISSN 1546-1718

Berthon, P.; Houlgatte, A.; Latil, A.& Cussenot, O. (2005). Clinical relevance of genetic instability in prostatic cells obtained by prostatic massage in early prostate

Varambally, S.; Cao, X.; Tchinda, J.; Kuefer, R.; Lee, C.; Montie, J.E.; Shah, R.B.; Pienta, K.J.; Rubin, M.A.& Chinnaiyan, A.M. (2005). Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. *Science*, Vol.310, No.5748,

J.& Nemunaitis, J. (2009). MicroRNA profile analysis of human prostate cancers.

Expression of a novel biomarker, EPCA, in adenocarcinomas and precancerous lesions in the prostate. *J Urol*, Vol.174, No.2, (Aug), pp.514-518, ISSN 0022-5347 Usher, P.A.; Thomsen, O.F.; Iversen, P.; Johnsen, M.; Brunner, N.; Hoyer-Hansen, G.;

Andreasen, P.; Dano, K.& Nielsen, B.S. (2005). Expression of urokinase plasminogen activator, its receptor and type-1 inhibitor in malignant and benign prostate tissue. *Int J Cancer*, Vol.113, No.6, (Mar 1), pp.870-880, ISSN 0020-7136 van Gils, M.P.; Hessels, D.; van Hooij, O.; Jannink, S.A.; Peelen, W.P.; Hanssen, S.L.; Witjes,

J.A.; Cornel, E.B.; Karthaus, H.F.; Smits, G.A.; Dijkman, G.A.; Mulders, P.F.& Schalken, J.A. (2007). The time-resolved fluorescence-based PCA3 test on urinary sediments after digital rectal examination; a Dutch multicenter validation of the diagnostic performance. *Clin Cancer Res*, Vol.13, No.3, (Feb 1), pp.939-943, ISSN

Jing, X.; Ramnarayanan, K.; Brenner, J.C.; Yu, J.; Kim, J.H.; Han, B.; Tan, P.; Kumar-Sinha, C.; Lonigro, R.J.; Palanisamy, N.; Maher, C.A.& Chinnaiyan, A.M. (2008). Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. *Science*, Vol.322, No.5908, (Dec 12), pp.1695-

Ghosh, D.; Pienta, K.J.; Sewalt, R.G.; Otte, A.P.; Rubin, M.A.& Chinnaiyan, A.M. (2002). The polycomb group protein EZH2 is involved in progression of prostate

C.W.& Van Grunsven, E.G. (2001). Peroxisomal fatty acid alpha- and beta-oxidation in humans: enzymology, peroxisomal metabolite transporters and peroxisomal diseases. *Biochem Soc Trans*, Vol.29, No.Pt 2, (May), pp.250-267, ISSN 0300-5127 Whitman, E.J.; Groskopf, J.; Ali, A.; Chen, Y.; Blase, A.; Furusato, B.; Petrovics, G.; Ibrahim,

M.; Elsamanoudi, S.; Cullen, J.; Sesterhenn, I.A.; Brassell, S.; Rittenhouse, H.; Srivastava, S.& McLeod, D.G. (2008). PCA3 score before radical prostatectomy predicts extracapsular extension and tumor volume. *J Urol*, Vol.180, No.5, (Nov),

Varambally, S.; Cao, Q.; Mani, R.S.; Shankar, S.; Wang, X.; Ateeq, B.; Laxman, B.; Cao, X.;

Varambally, S.; Dhanasekaran, S.M.; Zhou, M.; Barrette, T.R.; Kumar-Sinha, C.; Sanda, M.G.;

cancer. *Nature*, Vol.419, No.6907, (Oct 10), pp.624-629, ISSN 0028-0836 Wanders, R.J.; Vreken, P.; Ferdinandusse, S.; Jansen, G.A.; Waterham, H.R.; van Roermund,

pp.1975-1978; discussion 1978-1979, ISSN 1527-3792

racemase as a tissue biomarker for prostate cancer. *JAMA*, Vol.287, No.13, (Apr 3), pp.1662-1670, ISSN 0098-7484


Saeki, N.; Gu, J.; Yoshida, T.& Wu, X. (2010). Prostate stem cell antigen: a Jekyll and Hyde molecule? *Clin Cancer Res*, Vol.16, No.14, (Jul 15), pp.3533-3538, ISSN 1078-0432 Saramaki, O.R.; Harjula, A.E.; Martikainen, P.M.; Vessella, R.L.; Tammela, T.L.& Visakorpi,

Schaefer, A.; Jung, M.; Mollenkopf, H.J.; Wagner, I.; Stephan, C.; Jentzmik, F.; Miller, K.;

Schroder, F.H.; Hugosson, J.; Roobol, M.J.; Tammela, T.L.; Ciatto, S.; Nelen, V.;

Shariat, S.F.; Roehrborn, C.G.; McConnell, J.D.; Park, S.; Alam, N.; Wheeler, T.M.& Slawin,

Spahn, M.; Kneitz, S.; Scholz, C.J.; Stenger, N.; Rudiger, T.; Strobel, P.; Riedmiller, H.&

Sreekumar, A.; Poisson, L.M.; Rajendiran, T.M.; Khan, A.P.; Cao, Q.; Yu, J.; Laxman, B.;

progression. *Nature*, Vol.457, No.7231, (Feb 12), pp.910-914, ISSN 1476-4687 Stott, S.L.; Lee, R.J.; Nagrath, S.; Yu, M.; Miyamoto, D.T.; Ulkus, L.; Inserra, E.J.; Ulman, M.;

Thomas, G.; Jacobs, K.B.; Yeager, M.; Kraft, P.; Wacholder, S.; Orr, N.; Yu, K.; Chatterjee, N.;

*Cancer*, Vol.127, No.2, (Jul 15), pp.394-403, ISSN 1097-0215

Vol.2, No.25, (Mar 31), pp.25ra23, ISSN 1946-6242

pp.1662-1670, ISSN 0098-7484

pp.1166-1176, ISSN 1097-0215

No.13, (Mar 26), pp.1320-1328, ISSN 1533-4406

1078-0432

1527-7755

racemase as a tissue biomarker for prostate cancer. *JAMA*, Vol.287, No.13, (Apr 3),

T. (2008). TMPRSS2:ERG fusion identifies a subgroup of prostate cancers with a favorable prognosis. *Clin Cancer Res*, Vol.14, No.11, (Jun 1), pp.3395-3400, ISSN

Lein, M.; Kristiansen, G.& Jung, K. (2010). Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma. *Int J Cancer*, Vol.126, No.5, (Mar 1),

Kwiatkowski, M.; Lujan, M.; Lilja, H.; Zappa, M.; Denis, L.J.; Recker, F.; Berenguer, A.; Maattanen, L.; Bangma, C.H.; Aus, G.; Villers, A.; Rebillard, X.; van der Kwast, T.; Blijenberg, B.G.; Moss, S.M.; de Koning, H.J.& Auvinen, A. (2009). Screening and prostate-cancer mortality in a randomized European study. *N Engl J Med*, Vol.360,

K.M. (2007). Association of the circulating levels of the urokinase system of plasminogen activation with the presence of prostate cancer and invasion, progression, and metastasis. *J Clin Oncol*, Vol.25, No.4, (Feb 1), pp.349-355, ISSN

Kneitz, B. (2010). Expression of microRNA-221 is progressively reduced in aggressive prostate cancer and metastasis and predicts clinical recurrence. *Int J* 

Mehra, R.; Lonigro, R.J.; Li, Y.; Nyati, M.K.; Ahsan, A.; Kalyana-Sundaram, S.; Han, B.; Cao, X.; Byun, J.; Omenn, G.S.; Ghosh, D.; Pennathur, S.; Alexander, D.C.; Berger, A.; Shuster, J.R.; Wei, J.T.; Varambally, S.; Beecher, C.& Chinnaiyan, A.M. (2009). Metabolomic profiles delineate potential role for sarcosine in prostate cancer

Springer, S.; Nakamura, Z.; Moore, A.L.; Tsukrov, D.I.; Kempner, M.E.; Dahl, D.M.; Wu, C.L.; Iafrate, A.J.; Smith, M.R.; Tompkins, R.G.; Sequist, L.V.; Toner, M.; Haber, D.A.& Maheswaran, S. (2010). Isolation and characterization of circulating tumor cells from patients with localized and metastatic prostate cancer. *Sci Transl Med*,

Welch, R.; Hutchinson, A.; Crenshaw, A.; Cancel-Tassin, G.; Staats, B.J.; Wang, Z.; Gonzalez-Bosquet, J.; Fang, J.; Deng, X.; Berndt, S.I.; Calle, E.E.; Feigelson, H.S.; Thun, M.J.; Rodriguez, C.; Albanes, D.; Virtamo, J.; Weinstein, S.; Schumacher, F.R.; Giovannucci, E.; Willett, W.C.; Cussenot, O.; Valeri, A.; Andriole, G.L.; Crawford, E.D.; Tucker, M.; Gerhard, D.S.; Fraumeni, J.F., Jr.; Hoover, R.; Hayes, R.B.; Hunter, D.J.& Chanock, S.J. (2008). Multiple loci identified in a genome-wide association study of prostate cancer. *Nat Genet*, Vol.40, No.3, (Mar), pp.310-315, ISSN 1546-1718


**2** 

*Poland* 

**The Influence of Obesity on Prostate Cancer** 

To date there were only a few risk factors for developing prostate cancer (Pca) like advanced age, skin color and family history (Crawford, 2003). For the long time obesity was considered a negative feature which may contribute to chronic diseases like hypertension or diabetes, but its relationship with cancers was unknown. Last years revealed the obvious truth that such relationship exists and may be very strong. The problem seems to be very

Over the past 25 years, the number of obese men has increased from 15% to 30% in USA. In 2000 66% of adults in U.S were classified as overweight or obese (Flegal et al., 2002) Nowadays no one denies that overweight and obesity is an independent risk factor for

Relationship with other cancers is still discussed especially in case of Pca. While the connection between obesity and chronic internal diseases is simple to explain, its relation to cancers is not so unequivocal. Most theories indicate the permanent chronic inflammation in

Dishormonose observed in obese consists of high levels of insulin, insulin growth factor – 1 (IGF-1) (Chan et al., 1998, 2002), leptin, estrogens, and low levels of androgens. Insulin and IGF -1 are strong mitosis activators which may explain such "oncopotential". On the other hand low levels of testosterone and high of estrogen should protect men from developing Pca. It is only a simple example why the relation between obesity and prostate cancer may

Several products are thought to be associated with increased risk for developing prostate cancer, others are known to act protectively. To the first group we may include saturated fats, red meat and dairy products (Kondo et al., 1994; Shirai, et al., 1997; Torniainen et al., 2007). In the second group we will find vitamin A, D and E, selenium, lycopene, fitoestrogens and isoflavones (Clark et al., 1998; Heinonen et al., 1998; Imaida et al., 2001; Kato et al., 2000; Schwartz et al., 1990). Vitamin A, D, E, selenium, lycopene and fitoestrogens are the compounds of fruits, vegetables, soya and tea. Vitamin A is known to improve cell apoptosis (Pienta et al., 1993; Young et al., 1994). Vitamin D facilitates cell differentiation (Hedlund et al., 1997). It was hypothesized that it may increase PSA

important given that obesity is very common, especially in western countries.

developing colon cancer or post-menopausal breast cancer.

obese which may contribute to oncogenesis.

**1. Introduction** 

be very complex.

**2. Nutrition** 

Piotr Bryniarski, Andrzej Paradysz and Mieczysław Fryczkowski *Medical University of Silesia in Katowice, Department of Urology in Zabrze* 

**Diagnosis and Treatment** 

