Document Type : Original Research
Department of Pathology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
Pediatric Urology and Regenerative Medicine Research Center, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Background & Objective: Some certain markers, including prostatic specific antigen (PSA), are being used to screen prostate cancer (PC), but none of them have sufficient sensitivity and specificity for evaluation of prognosis. Currently, genetic variants have found their place in the prognosis of PC. ETS-related gene (ERG) expression and its intensity have contradictory evidence regarding ERG expression with PC incidence or associating outcome. Our purpose was to survey the relationship of ERG expression and its intensity with PC and relative clinical outcome.
Methods: We studied the immunohistochemichal (IHC) expression of ERG in 101 radical prostatectomy specimens with PC of different histologic grades. All samples were chosen from pathology department of Sina hospital in Tehran-Iran from 2011 to 2018. Positive ERG expression and its association with Gleason score, preoperative PSA, metastasis status, stage and grade of tumors was evaluated.
Results: In total, ERG expression was observed in 42 cases (41.58%) and of these, 7 (16.66%) were categorized as weak, 13 (30.95%) moderate and 22(52.38%) as strong. There was no significant correlation between ERG expression and age, preoperative PSA, Gleason score, lymph node involvement, metastatic pattern, stage, and grade of the tumor (P>0.05). ERG expression frequency in the two groups of survived and expired patients was 42.85% and 0%, respectively; despite the noticeable difference, it was not statistically significance (P=0.264).
Conclusion: Evaluation of ERG expression and its intensity may have no essential role as an acceptable prognostic factor in Iranian’s population for anticipating whether PC itself or the outcomes accompanied. This relation is vigorously under the influence of geographical/ethnical features.
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- Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58(2):71-96. [DOI:10.3322/CA.2007.0010] [PMID]
- Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010;46(4):765-81. [DOI:10.1016/j.ejca.2009.12.014] [PMID]
- Wood DE. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Lung Cancer Screening. Thorac Surg Clin. 2015;25(2):185-97. [DOI:10.1016/j.thorsurg.2014.12.003] [PMID]
- Brawley OW. Trends in prostate cancer in the United States. J Natl Cancer Inst Monogr. 2012;2012(45):152-6. [DOI:10.1093/jncimonographs/lgs035] [PMID] [PMCID]
- Ross LE, Berkowitz Z, Ekwueme DU. Use of the prostate-specific antigen test among US men: findings from the 2005 National Health Interview Survey. Cancer Epidemiology and Prevention Biomarkers. 2008;17(3):636-44. [DOI:10.1158/1055-9965.EPI-07-2709] [PMID]
- Furusato B, Tan SH, Young D, Dobi A, Sun C, Mohamed AA, et al. ERG oncoprotein expression in prostate cancer: clonal progression of ERG-positive tumor cells and potential for ERG-based stratification. Prostate Cancer Prostatic Dis. 2010;13(3):228-37. [DOI:10.1038/pcan.2010.23] [PMID] [PMCID]
- Sirousbakht S, Rezakhaniha B. Effect of colonoscopy on prostate-specific antigen; new words about an old subject. International Journal of Cancer Management. 2018;11(7). [DOI:10.5812/ijcm.68919]
- Rezakhaniha B, Pour AN, Siroosbakhat S. Effect of cystoscopy on prostate-specific antigen, new words about old subject. Iranian Journal of Cancer Prevention. 2010;3(4).
- Denmeade SR, Isaacs JT. A history of prostate cancer treatment. Nat Rev Cancer. 2002;2(5):389-96. [DOI:10.1038/nrc801] [PMID] [PMCID]
- Feldman BJ, Feldman D. The development of androgen-independent prostate cancer. Nat Rev Cancer. 2001;1(1):34-45. [DOI:10.1038/35094009] [PMID]
- Petrovics G, Liu A, Shaheduzzaman S, Furusato B, Sun C, Chen Y, et al. Frequent overexpression of ETS-related gene-1 (ERG1) in prostate cancer transcriptome. Oncogene. 2005;24(23):3847-52. [DOI:10.1038/sj.onc.1208518] [PMID]
- Kumar-Sinha C, Tomlins SA, Chinnaiyan AM. Recurrent gene fusions in prostate cancer. Nat Rev Cancer. 2008;8(7):497-511. [DOI:10.1038/nrc2402] [PMID] [PMCID]
- Reddy ES, Rao VN, Papas TS. The erg gene: a human gene related to the ets oncogene. Proc Natl Acad Sci U S A. 1987;84(17):6131-5. [DOI:10.1073/pnas.84.17.6131] [PMID] [PMCID]
- Rao VN, Papas TS, Reddy ES. erg, a human ets-related gene on chromosome 21: alternative splicing, polyadenylation, and translation. Science. 1987;237(4815):635-9. [DOI:10.1126/science.3299708] [PMID]
- Din NU, Qureshi A, Mansoor S. Utility of p63 immunohistochemical stain in differentiating urothelial carcinomas from adenocarcinomas of prostate. Indian Journal of Pathology and Microbiology. 2011;54(1):59. [DOI:10.4103/0377-4929.77326] [PMID]
- He H, Magi-Galluzzi C, Li J, Carver P, Falzarano S, Smith K, et al. The diagnostic utility of novel immunohistochemical marker ERG in the workup of prostate biopsies with "atypical glands suspicious for cancer". The American journal of surgical pathology. 2011;35(4):608-14. [DOI:10.1097/PAS.0b013e31820bcd2d] [PMID]
- Lotan TL, Gupta NS, Wang W, Toubaji A, Haffner MC, Chaux A, et al. ERG gene rearrangements are common in prostatic small cell carcinomas. Mod Pathol. 2011;24(6):820-8. [DOI:10.1038/modpathol.2011.7] [PMID] [PMCID]
- Duterque-Coquillaud M, Niel C, Plaza S, Stehelin D. New human erg isoforms generated by alternative splicing are transcriptional activators. Oncogene. 1993;8(7):1865-73.
- Miettinen M, Wang Z-F, Paetau A, Tan S-H, Dobi A, Srivastava S, et al. ERG transcription factor as an immunohistochemical marker for vascular endothelial tumors and prostatic carcinoma. The American journal of surgical pathology. 2011;35(3):432-41. [DOI:10.1097/PAS.0b013e318206b67b] [PMID] [PMCID]
- Leyten GH, Hessels D, Jannink SA, Smit FP, de Jong H, Cornel EB, et al. Prospective multicentre evaluation of PCA3 and TMPRSS2-ERG gene fusions as diagnostic and prognostic urinary biomarkers for prostate cancer. European urology. 2014;65(3):534-42. [DOI:10.1016/j.eururo.2012.11.014] [PMID]
- Verdu M, Trias I, Roman R, Rodon N, Garcia-Pelaez B, Calvo M, et al. ERG expression and prostatic adenocarcinoma. Virchows Arch. 2013;462(6):639-44. [DOI:10.1007/s00428-013-1415-3] [PMID]
- Yaskiv O, Zhang X, Simmerman K, Daly T, He H, Falzarano S, et al. The utility of ERG/P63 double immunohistochemical staining in the diagnosis of limited cancer in prostate needle biopsies. Am J Surg Pathol. 2011;35(7):1062-8. [DOI:10.1097/PAS.0b013e318215cc03] [PMID]
- Qi M, Yang X, Zhang F, Lin T, Sun X, Li Y, et al. ERG rearrangement is associated with prostate cancer-related death in Chinese prostate cancer patients. PloS one. 2014;9(2):e84959. [DOI:10.1371/journal.pone.0084959] [PMID] [PMCID]
- Xu B, Chevarie-Davis M, Chevalier S, Scarlata E, Zeizafoun N, Dragomir A, et al. The prognostic role of ERG immunopositivity in prostatic acinar adenocarcinoma: a study including 454 cases and review of the literature. Hum Pathol. 2014;45(3):488-97. [DOI:10.1016/j.humpath.2013.10.012] [PMID]
- Bokhorst LP, Roobol MJ, Bangma CH, van Leenders GJ. Effect of pathologic revision and Ki67 and ERG immunohistochemistry on predicting radical prostatectomy outcome in men initially on active surveillance. Prostate. 2017;77(10):1137-43. [DOI:10.1002/pros.23372] [PMID]
- Pan XY, Tan JY, Nie L, Yin XX, Gong J, Chen XQ, et al. [Prognostic Significance of ERG Gene Rearrangement and Protein Expression in Prostate Cancer]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2017;48(1):66-70.
- Taris M, Irani J, Blanchet P, Multigner L, Cathelineau X, Fromont G. ERG expression in prostate cancer: the prognostic paradox. Prostate. 2014;74(15):1481-7. [DOI:10.1002/pros.22863] [PMID]
- Koide H, Kimura T, Inaba H, Sato S, Iwatani K, Yorozu T, et al. Comparison of ERG and SPINK1 expression among incidental and metastatic prostate cancer in Japanese men. The Prostate. 2019;79(1):3-8. [DOI:10.1002/pros.23705] [PMID]
- Bismar TA, Hegazy S, Feng Z, Yu D, Donnelly B, Palanisamy N, et al. Clinical utility of assessing PTEN and ERG protein expression in prostate cancer patients: a proposed method for risk stratification. J Cancer Res Clin Oncol. 2018;144(11):2117-25. [DOI:10.1007/s00432-018-2730-5] [PMID]