JCT  Vol.4 No.3 , May 2013
Correlation of Urinary Engrailed-2 Levels to Tumour Volume and Pathological Stage in Men Undergoing Radical Prostatectomy
Abstract: The aim of this study was to assess the relationship between pre-prostatectomy urinary Engrailed-2 (EN2), a transcription factor secreted by prostate cancer cells, with tumour volume and pathological characteristics in resected prostate specimens. First pass urine samples (10 ml) without prior prostatic massage were collected and stored at –80°C. EN2 levels were measured using an enzyme-linked immunoabsorbent assay. Tumour volume in the prostatectomy specimens was determined histologically. 57 men undergoing RP in one urological cancer network were evaluated. EN2 was detected in 85% of RP patients. EN2 correlated with tumour volume (but not total prostatic volume) in a linear regression analysis, with increasing pathological T stage and margin positivity. Using three “cutoff levels” of tumour volume (0.5 ml, 1.3 ml and 2.5 ml) to define “significant disease”, men with “significant disease” had markedly higher levels of urinary EN2 (p < 0.001 for each cut off level). Levels of urinary EN2 may be useful in predicting tumour volume in men with prostate cancer by potentially identifying men with small volume “insignificant” disease. This study justifies a larger multicentre evaluation of urinary EN2 levels as a biomarker of PC significance using cancer volume, pathological and PSA criteria.
Cite this paper: H. Pandha, S. Javed, P. Sooriakumaran, S. Bott, B. Montgomery, A. Hutton, C. Eden, C. Eden, S. Langley and R. Morgan, "Correlation of Urinary Engrailed-2 Levels to Tumour Volume and Pathological Stage in Men Undergoing Radical Prostatectomy," Journal of Cancer Therapy, Vol. 4 No. 3, 2013, pp. 726-733. doi: 10.4236/jct.2013.43089.

[1]   R. W. Veltri, M. C. Miller, G. J. O’dowd and A. W. Partin, “Impact of Age on Total and Complexed ProstateSpecific Antigen Cut offs in a Contemporary Referral Series of Men with Prostate Cancer,” Urology, Vol. 60, No. 4, 2002, pp. 47-52. doi:10.1016/S0090-4295(02)01695-3

[2]   H. Lilja, D. Ulmert and A. J. Vickers, “Prostate-Specific Antigen and Prostate Cancer: Prediction, Detection and Monitoring,” Nature Reviews: Cancer, Vol. 8, No. 4, 2008, pp. 268-278. doi:10.1038/nrc2351

[3]   S. M. Falzarano and C. Magi-Galluzzi, “Prostate Cancer Staging and Grading at Radical Prostatectomy over Time,” Advances in Anatomic Pathology, Vol. 18, No. 2, 2011, pp. 159-164. doi:10.1097/PAP.0b013e31820cb506

[4]   J. E. Oesterling, S. J. Jacobsen, G. G. Klee, et al., “Free, Complexed and Total Serum Prostate Specific Antigen: The Establishment of Appropriate Reference Ranges for Their Concentrations and Ratios,” The Journal of Urology, Vol. 154, No. 3, 1995, pp. 1090-1095. doi:10.1016/S0022-5347(01)66984-2

[5]   S. F. Shariat, A. Semjonow, H. Lilja, et al., “Tumour Markers in Prostate Cancer I: Blood-Based Markers,” Acta Oncologica, Vol. 50, No. S1, 2011, pp. 61-75. doi:10.3109/0284186X.2010.542174

[6]   R. Morgan, A. Boxall, A. Bhatt, et al., “Engrailed-2 (EN2): A Tumor Specific Urinary Biomarker for the Early Diagnosis of Prostate Cancer,” Clinical Cancer Research, Vol. 17, No. 5, 2011, pp. 1090-1098. doi:10.1158/1078-0432.CCR-10-2410

[7]   H. Pandha, K. D. Sorensen, T. F. Orntoft, et al., “Urinary Engrailed-2 (EN2) Levels Predict Tumour Volume in Men Undergoing Radical Prostatectomy for Prostate Cancer,” BJU International, Vol. 110, No. 6, 2012, pp. E287-E292. doi:10.1111/j.1464-410X.2012.11208.x

[8]   J. I. Epstein, P. C. Walsh and H. B. Carter, “Dedifferentiation of Prostate Cancer Grade with Time in Men Followed Expectantly for Stage T1c Disease,” The Journal of Urology, Vol. 166, No. 5, 2011, pp. 1688-1691.

[9]   T. Wolters, M. J. Roobol, P. J. van Leeuwen, et al., “A Critical Analysis of the Tumour Volume Threshold for Clinically Insignificant Prostate Cancer Using a Data Set of a Randomized Screening Trial,” The Journal of Urology, Vol. 185, No. 1, 2011, pp. 121-125. doi:10.1016/j.juro.2010.08.082

[10]   H. U. Ahmed, M. Arya, A. Freeman, et al., “Do LowGrade and Low-Volume Prostate Cancers Bear the Hallmarks of Malignancy?” The Lancet Oncology, Vol. 13, No. 11, 2012, pp. e509-e517.

[11]   L. Klotz, “Active Surveillance for Prostate Cancer: A Review,” Current Urology Reports, Vol. 11, No. 3, 2010, pp. 165-171. doi:10.1007/s11934-010-0110-z

[12]   L. Salomon, O. Levrel, A. G. Anastasiadis, et al., “Prognostic Significance of Tumour Volume after Radical Prostatectomy: A Multivariate Analysis of Pathological Prognostic Factors,” European Urology, Vol. 43, No. 1, 2003, pp. 39-44. doi:10.1016/S0302-2838(02)00493-1

[13]   J. R. Prensner, M. A. Rubin, J. T. Wei, et al., “Beyond PSA: The Next Generation of Prostate Cancer Biomarkers,” Science Translational Medicine, Vol. 4, No. 127, 2012, Article ID: 127rv3.

[14]   G. Ploussard, X. Durand, E. Xylinas, et al., “Prostate Cancer Antigen 3 Score Accurately Predicts Tumour Volume and Might Help in Selecting Prostate Cancer Patients for Active Surveillance,” European Urology, Vol. 59, No. 3, 2011, pp. 422-429. doi:10.1016/j.eururo.2010.11.044

[15]   H. Nakanishi, J. Groskopf, H. A. Fritsche, et al., “PCA3 Molecular Urine Assay Correlates with Prostate Cancer Tumor Volume: Implication in Selecting Candidates for Active Surveillance,” The Journal of Urology, Vol. 179 No. 5, 2008, pp. 1804-1809. doi:10.1016/j.juro.2008.01.013

[16]   E. J. Whitman, J. Groskopf, A. Ali, et al., “PCA3 Score before Radical Prostatectomy Predicts Extracapsular Extension and Tumor Volume,” The Journal of Urology, Vol. 180, No. 5, 2008, pp. 1975-1979. doi:10.1016/j.juro.2008.07.060

[17]   M. P. van Gils, D. Hessels, C. A. Hulsbergen-van de Kaa, et al., “Detailed Analysis of Histopathological Parameters in Radical Prostatectomy Specimens and PCA3 Urine Test Results,” The Prostate, Vol. 68, No. 11, 2008, pp. 1215-1222. doi:10.1002/pros.20781

[18]   D. Hessels, M. P. van Gils, O. van Hooij, et al., “Predictive Value of PCA3 in Urinary Sediments in Determining Clinico-Pathological Characteristics of Prostate Cancer,” The Prostate, Vol. 70, No. 1, 2010, pp. 10-16. doi:10.1002/pros.21032

[19]   M. Auprich, F. K. Chun, J. F. Ward, et al., “Critical Assessment of Preoperative Urinary Prostate Cancer Antigen 3 on the Accuracy of Prostate Cancer Staging,” European Urology, Vol. 59, No. 1, 2011, pp. 96-105. doi:10.1016/j.eururo.2010.10.024

[20]   M. W. Kattan, “Do We Need More Nomograms for Predicting Outcomes in Patients with Prostate Cancer?” Nature Reviews Urology, Vol. 5, No. 7, 2008, pp. 366-367. doi:10.1038/ncpuro1128