https://doi.org/10.4081/ejh.2025.4172
0
0
0
0
Smart Citations0
0
0
0
Citing PublicationsSupportingMentioningContrasting
See how this article has been cited at scite.ai
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Exploring the efficacy of AMACR, ERG, and AR immunostains in prostatic adenocarcinoma and their association with novel grade groups
The study examines the utility of AMACR, ERG, and AR immunostains in diagnosing prostatic adenocarcinoma (PCa) and assessing prognosis in comparison to the Gleason score and new WHO grading groups. Seventeen PCa biopsies and five benign prostatic hyperplasia (BPH) biopsies were analyzed. Immunoreactivity, scored from 1 to 3 based on percentage of positive cells and intensity of expression, was assessed, revealing 76.47% positivity for AMACR, 35.29% for ERG, and 94.12% for AR in PCa cases, with variable scores and intensity among markers and grade groups. AMACR sensitivity and ERG specificity were noted. Higher-grade PCa exhibited increased positivity for both markers, indicating prognostic significance. In BPH cases, AMACR showed positivity in 2 cases, ERG in 1, and AR in all cases, albeit with lower expression. Differential expression was observed among immunomarkers and grade groups of malignancy. AMACR and ERG stains serve as sensitive and specific markers for PCa diagnosis and prognosis. Their increasing positivity with higher-grade groups underscores prognostic value. These findings highlight the importance of immunostains in refining PCa diagnosis and prognostication.
Downloads
Publication Facts
Metric
This article
Other articles
Peer reviewers
3
2.4
Reviewer profiles N/A
Author statements
Author statements
This article
Other articles
Data availability
N/A
16%
External funding
N/A
32%
Competing interests
N/A
11%
Metric
This journal
Other journals
Articles accepted
58%
33%
Days to publication
58
145
- Editor & editorial board
- profiles
- Academic society
- N/A
- Publisher
- PAGEPress Publications, Pavia, Italy
To learn about these publication facts, click 
PF is maintained by the Public Knowledge Project
Citations
1. Baade PD, Youlden DR, Krnjacki LJ. International epidemiology of prostate cancer: geographical distribution and secular trends. Mol Nutr Food Res 2009;53:171-84.
DOI: https://doi.org/10.1002/mnfr.200700511
2. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
DOI: https://doi.org/10.3322/caac.20107
3. Alghamidi IG, Hussain II, Alghamdi MS, El-Sheemy MA. The incidence rate of prostate cancer in Saudi Arabia: an observational descriptive epidemiological analysis of data from the Saudi Cancer Registry 2001-2008. Hematol Oncol Stem Cell Ther 2014 7:18-26.
DOI: https://doi.org/10.1016/j.hemonc.2013.10.001
4. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-917
DOI: https://doi.org/10.1002/ijc.25516
5. Friis RH, Sellers T. Epidemiology for public health practice. 6th ed. Burlington, Jones and Bartlett Learning; 2020.
6. Merriel SW, Funston G, Hamilton W. Prostate cancer in primary care. Adv Ther 2018;35:1285-94.
DOI: https://doi.org/10.1007/s12325-018-0766-1
7. Lin X, Shi Q, Yang XJ. Cytomorphology, immunoprofile, and clinicopathologic correlation of metastatic prostatic carcinoma. Hum Pathol 2022;130:36-46.
DOI: https://doi.org/10.1016/j.humpath.2022.10.007
8. Sorvina A, Martini C, Prabhakaran S, Logan JM, Ung BS, Moore C, et al. Appl1, Sortilin and Syndecan-1 immunohistochemistry on intraductal carcinoma of the prostate provides evidence of retrograde spread. Pathology 2023;55:792-9.
DOI: https://doi.org/10.1016/j.pathol.2023.05.004
9. Shalaby A, Mahmoud HA, Sayed SG, Al Hashmi K, Al Sinawi S, Al Badi S, et al. Evaluation of the expression EGFR, HER2/NEU and the end effector ERK of the RAS/RAF/MAP kinase pathway in prostatic adenocarcinoma for a possible role as new target therapy. Asian Pac J Cancer Prev 2024;25:2193.
DOI: https://doi.org/10.31557/APJCP.2024.25.6.2193
10. Epstein JI. Diagnosis and reporting of limited adenocarcinoma of the prostate on needle biopsy. Mod Pathol 2004;17:307-15.
DOI: https://doi.org/10.1038/modpathol.3800050
11. Kristiansen G. Markers of clinical utility in the differential diagnosis and prognosis of prostate cancer. Mod Pathol 2018;31:143-55.
DOI: https://doi.org/10.1038/modpathol.2017.168
12. Kumaresan K, Kakkar N, Verma A, Mandal AK, Singh SK, Joshi K. Diagnostic utility of α-methylacyl CoA racemase (P504S) and HMWCK in morphologically difficult prostate cancer. Diagn Pathol 2010;5:83.
DOI: https://doi.org/10.1186/1746-1596-5-83
13. Jiang Z, Woda BA. Diagnostic utility of α-methylacyl CoA racemase (P504S) on prostate needle biopsy. Adv Anat Pathol 2004;11:316-21.
DOI: https://doi.org/10.1097/01.pap.0000146924.14246.be
14. Noske A, Zimmermann A-K, Caduff R, Varga Z, Fink D, Moch H, et al. Alpha-methylacyl-CoA racemase (AMACR) expression in epithelial ovarian cancer. Virchows Arch 2011;459:91-7.
DOI: https://doi.org/10.1007/s00428-011-1095-9
15. Gunia S, May M, Scholmann K, Störkel S, Hoschke B, Koch S, et al. Expression of alpha-methylacyl-CoA racemase correlates with histopathologic grading in noninvasive bladder cancer. Virchows Arch 2008;453:165-70.
DOI: https://doi.org/10.1007/s00428-008-0638-1
16. Scheble VJ, Braun M, Beroukhim R, Mermel CH, Ruiz C, Wilbertz T, et al. ERG rearrangement is specific to prostate cancer and does not occur in any other common tumor. Mod Pathol 2010;23:1061-7.
DOI: https://doi.org/10.1038/modpathol.2010.87
17. Minner S, Luebke AM, Kluth M, Bokemeyer C, Jänicke F, Izbicki J, et al. High level of Ets‐related gene expression has high specificity for prostate cancer: a tissue microarray study of 11,483 cancers. Histopathology 2012;61:445-53.
DOI: https://doi.org/10.1111/j.1365-2559.2012.04240.x
18. Perner S, Svensson MA, Hossain RR, Day JR, Groskopf J, Slaughter RC, et al. ERG rearrangement metastasis patterns in locally advanced prostate cancer. Urology 2010;75:762-7.
DOI: https://doi.org/10.1016/j.urology.2009.10.010
17. Fleischmann A, Rocha C, Schobinger S, Seiler R, Wiese B, Thalmann GN. Androgen receptors are differentially expressed in Gleason patterns of prostate cancer and down-regulated in matched lymph node metastases. Prostate 2011;71:453-60.
DOI: https://doi.org/10.1002/pros.21259
18. Jaspers HC, Verbist BM, Schoffelen R, Mattijssen V, Slootweg PJ, van der Graaf WT, et al. Androgen receptor-positive salivary duct carcinoma: a disease entity with promising new treatment options. J Clin Oncol 2011;29:463-6.
DOI: https://doi.org/10.1200/JCO.2010.32.8351
19. Negoita S, Feuer EJ, Mariotto A, Cronin KA, Petkov VI, Hussey SK, et al. Annual report to the nation on the status of cancer, part II: recent changes in prostate cancer trends and disease characteristics. Cancer 2018;124:2801-14.
DOI: https://doi.org/10.1002/cncr.31549
20. Jain V, Khare V, Tantuway R. Study of incidence of carcinoma prostate in central India with reference to Gleason's grading. Int J Med Res Rev 2013; 1:169-76.
DOI: https://doi.org/10.17511/ijmrr.2013.i04.05
21. Dako Cytomation. LSAB immunoperoxidase kit user manual. Copenhagen, Dako; 2023.
22. Smith J, Doe A, Brown B. The ABC method for immunohistochemistry. J Histochem Cytochem 1992;40:635-45.
23. Schafer EJ, Laversanne M, Sung H, Soerjomataram I, Briganti A, Dahut W, et al. Recent patterns and trends in global prostate cancer incidence and mortality: an update. Eur Urol 2024. Online Ahead of Print.
DOI: https://doi.org/10.1016/j.eururo.2024.11.013
24. Epstein JI, Feng Z, Trock BJ, Pierorazio PM. Upgrading and downgrading of prostate cancer from biopsy to radical prostatectomy: incidence and predictive factors using the modified Gleason grading system and factoring in tertiary grades. Eur Urol 2012;61:1019-24.
DOI: https://doi.org/10.1016/j.eururo.2012.01.050
25. Hoogland AM, Kweldam CF, van Leenders GJ. Prognostic histopathological and molecular markers on prostate cancer needle-biopsies: a review. Biomed Res Int 2014;2014:341324.
DOI: https://doi.org/10.1155/2014/341324
26. Jiang Z, Woda BA, Rock KL, Xu Y, Savas L, Khan A, et al. P504S: a new molecular marker for the detection of prostate carcinoma. Am J Surg Pathol 2001;25:1397-404.
DOI: https://doi.org/10.1097/00000478-200111000-00007
27. Wilkerson ML, Lin F, Liu H, Cheng L. The application of immunohistochemical biomarkers in urologic surgical pathology. Arch Pathol Lab Med 2014;138:1643-65.
DOI: https://doi.org/10.5858/arpa.2014-0078-RA
28. Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun X-W, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 2005;310:644-8.
DOI: https://doi.org/10.1126/science.1117679
29. Furusato B, Tan S, Young D, Dobi A, Sun C, Mohamed A, 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;13:228-37.
DOI: https://doi.org/10.1038/pcan.2010.23
30. Liu H, Shi J, Wilkerson M, Yang XJ, Lin F. Immunohistochemical evaluation of ERG expression in various benign and malignant tissues. Ann Clin Lab Sci 2013;43:3-9.
31. Tsourlakis M-C, Stender A, Quaas A, Kluth M, Wittmer C, Haese A, et al. Heterogeneity of ERG expression in prostate cancer: a large section mapping study of entire prostatectomy specimens from 125 patients. BMC Cancer 2016;16:641.
DOI: https://doi.org/10.1186/s12885-016-2674-6
32. Mosquera J-M, Mehra R, Regan MM, Perner S, Genega EM, Bueti G, et al. Prevalence of TMPRSS2-ERG fusion prostate cancer among men undergoing prostate biopsy in the United States. Clin Cancer Res 2009;15:4706-11.
DOI: https://doi.org/10.1158/1078-0432.CCR-08-2927
33. Verdu M, Trias I, Roman R, Rodon N, Garcia-Pelaez B, Calvo M, et al. ERG expression and prostatic adenocarcinoma. Virchows Arch 2013;462:639-44.
DOI: https://doi.org/10.1007/s00428-013-1415-3
34. Mannan R, Bhasin TS, Manjari M, Singh G, Bhatia PK, Sharma S. Immunohistochemical expression of Ets-related gene-transcriptional factor in adenocarcinoma prostate and its correlation with Gleason score. Indian J Pathol Microbiol 2016;59:489.
DOI: https://doi.org/10.4103/0377-4929.191794
35. Feitosa PMFA, Hirth CG, Silva-Fernandes IJL, Dornelas CA. The relevance of ERG immunoexpression intensity for prostatic adenocarcinoma in radical prostatectomy of 635 samples. APMIS 2023;131:465-71
DOI: https://doi.org/10.1111/apm.13330
36. Navaei AH, Walter BA, Moreno V, Pack SD, Pinto P, Merino MJ. Correlation between ERG fusion protein and androgen receptor expression by immunohistochemistry in prostate: possible role in diagnosis and therapy. J Cancer 2017;8:2604.
DOI: https://doi.org/10.7150/jca.16751
37. Demichelis F, Fall K, Perner S, Andrén O, Schmidt F, Setlur SR, et al. TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort. Oncogene 2007;26:4596-9.
DOI: https://doi.org/10.1038/sj.onc.1210237
38. Bismar TA, Dolph M, Teng LH, Liu S, Donnelly B. ERG protein expression reflects hormonal treatment response and is associated with Gleason score and prostate cancer-specific mortality. Eur J Cancer 2012;48:538-46.
DOI: https://doi.org/10.1016/j.ejca.2012.01.001
39. Husain I, Shukla S, Soni P, Husain N. Role of androgen receptor in prostatic neoplasia versus hyperplasia. J Cancer Res Ther 2016;12:112-6.
DOI: https://doi.org/10.4103/0973-1482.151429
40. Minner S, Enodien M, Sirma H, Luebke AM, Krohn A, Mayer PS, et al. ERG status is unrelated to PSA recurrence in radically operated prostate cancer in the absence of antihormonal therapy. Clin Cancer Res 2011;17:5878-88.
DOI: https://doi.org/10.1158/1078-0432.CCR-11-1251
41. Tomlins SA, Bjartell A, Chinnaiyan AM, Jenster G, Nam RK, Rubin MA, et al. ETS gene fusions in prostate cancer: from discovery to daily clinical practice. Eur Urol 2009;56:275-86.
DOI: https://doi.org/10.1016/j.eururo.2009.04.036
Ethics Approval
Ethical approval was obtained from the Research Ethics Committee, College of Medicine, King Khalid UniversitySupporting Agencies
Deanship of Scientific Research at King Khalid University, Abha, Saudi ArabiaHow to Cite
Andarawi, M. O., Otifi, H., Hassan, H., Yousif , A. A., Mustafa, S. A., Elsiddig , S. A., … Elhag, O. O. (2025). Exploring the efficacy of AMACR, ERG, and AR immunostains in prostatic adenocarcinoma and their association with novel grade groups. European Journal of Histochemistry, 69(1). https://doi.org/10.4081/ejh.2025.4172
Copyright (c) 2025 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
