Document Type : Original Research

Authors

1 Department of Pathology, Faculty of Medicine, Shahed University, Tehran, Iran

2 Medical Students Research Committee, Shahed University, Tehran, Iran

Abstract

Background & Objective: Prostatic adenocarcinoma (PAC) is one of the most common tumors worldwide. Immunohistochemical expression of cytokeratins has been evaluated in the diagnosis and prognosis of tumors. The aim of the present study is the evaluation of Cytokeratin-7 (Ck-7) and Cytokeratin-19 (Ck-19) expression and its relationship with Gleason score in patients with PAC.
Methods: In this cross-sectional study, 78 samples from 78 patients with PAC referred to Mostafa Khomeini Hospital were gathered. Samples were immunohistochemically stained by Ck-7 and Ck-19 markers. The percentage of each marker in tumor cells was determined, and its relationship with Gleason scores and Gleason grade groups was analysed by SPSS version 24.
Results: The expression of Ck-7 and Ck-19 were seen in 37.2% and 82.1% of samples, respectively. The mean of Ck-7 expression in tumor cells was 4.98%±7.19 (ranged 0 to 26%), while the mean of Ck-19 expression was 41.02%±23.36 (ranged 0 to 78%). There was no relationship between Ck-7 expression with Gleason scores and Gleason grade groups. However, Ck-19 expression was increased in higher Gleason scores and Gleason grade groups (P<0.001). No relationship was found between age and Ck-7 (P=0.309) and Ck-19 (P=0.375).
Conclusion: The Ck-7 expression in PAC samples is weak and focal and had no relationship with the Gleason scores and Gleason grade groups. However, Ck-19 expression in PAC was high and was associated with tumor dedifferentiation of samples. There was no relationship between the expression of both markers with the patient's age.

Keywords

Main Subjects

  1. Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RG, Barzi A, et al. Colorectal cancer statistics, 2017. CA: Cancer J Clin. 2017;67(3):177-93. [DOI:10.3322/caac.21395] [PMID]
  2. Gandaglia G, Leni R, Bray F, Fleshner N, Freedland SJ, Kibel A, et al. Epidemiology and prevention of prostate cancer. Euro Urol Oncol. 2021. [DOI:10.1016/j.euo.2021.09.006] [PMID]
  3. Tomlins SA, Rubin MA, Chinnaiyan AM. Integrative biology of prostate cancer progression. Annu Rev Pathol Mech Dis. 2006;1:243-71. [DOI:10.1146/annurev.pathol.1.110304.100047] [PMID]
  4. Murray TB. The pathogenesis of prostate cancer. Exon Publications. 2021:29-41. [DOI:10.36255/exonpublications.prostatecancer.pathogenesis.2021] [PMID]
  5. Sehn JK. Prostate cancer pathology: recent updates and controversies. Missouri Med. 2018;115(2):151.
  6. Aghamir SMK, Shafiee G, Ebrahimi M, Yarmohammadi H, Razmande R, Ahmadi H, et al. Comparison on diagnostic accuracy of prostate cancer detection tools: a systematic review and meta-analysis. Transl Res Urol. 2019;1(1):27-39.
  7. Dere Y, Altınboğa AA, Yaldır E, Bal K, Tosun K, Sarı A. Correlation of Prognostic Gleason Grade Grouping and Histopathological Parameters: Can the" New System" Reflect the Pathological Perspective for Prognosis? 2018.
  8. Lattouf JB, Saad F. Gleason score on biopsy: is it reliable for predicting the final grade on pathology? BJU Int. 2002;90(7):694-8. [DOI:10.1046/j.1464-410X.2002.02990.x] [PMID]
  9. Hammerich KH, Ayala GE, Wheeler TM. Application of immunohistochemistry to the genitourinary system (prostate, urinary bladder, testis, and kidney). Arch Pathol Lab Med. 2008;132(3):432-40. [DOI:10.5858/2008-132-432-AOITTG] [PMID]
  10. Eggener SE, Rumble RB, Armstrong AJ, Morgan TM, Crispino T, Cornford P, et al. Molecular biomarkers in localized prostate cancer: ASCO guideline. J Clin Oncol. 2020;38(13):1474-94. [DOI:10.1200/JCO.19.02768] [PMID]
  11. Chu P, Wu E, Weiss LM. Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol. 2000;13(9):962-72. [DOI:10.1038/modpathol.3880175] [PMID]
  12. Cooper D, Schermer A, Sun TT. Classification of human epithelia and their neoplasms using monoclonal antibodies to keratins: strategies, applications, and limitations. Lab Invest. 1985;52(3):243-56.
  13. Dum D, Menz A, Völkel C, De Wispelaere N, Hinsch A, Gorbokon N, et al. Cytokeratin 7 and cytokeratin 20 expression in cancer: A tissue microarray study on 15,424 cancers. Exp Mol Pathol. 2022;126:104762. [DOI:10.1016/j.yexmp.2022.104762] [PMID]
  14. Lam K, Lui M, Lo C. Cytokeratin expression profiles in thyroid carcinomas. Euro J Surg Oncol. 2001;27(7):631-5. [DOI:10.1053/ejso.2001.1203] [PMID]
  15. Xin L. Cells of origin for prostate cancer. Prostate Cancer. 2019:67-86. [DOI:10.1007/978-3-030-32656-2_4] [PMID]
  16. Gheitasi R, Sadeghi E, Jafari M. Comparison of immunohistochemistry expression of CK7, HMWK and PSA in high-grade prostatic adenocarcinoma and bladder transitional cell carcinoma. Iran J Pathol. 2021;16(1):33. [DOI:10.30699/ijp.2020.123998.2353] [PMID] []
  17. Mhawech P, Uchida T, Pelte M-F. Immunohistochemical profile of high-grade urothelial bladder carcinoma and prostate adenocarcinoma. Hum Pathol. 2002;33(11):1136-40. [DOI:10.1053/hupa.2002.129416] [PMID]
  18. Adisa JO, Egbujo EC, Ibrahim B, Musa B, Madukwe J. Expression of some selected cytokeratins and Ki67 protein in prostatic tumor: can these be used as tumor markers. Pan Afr Med J. 2015;20(1). [DOI:10.11604/pamj.2015.20.46.3926]
  19. Goldstein NS. Immunophenotypic characterization of 225 prostate adenocarcinomas with intermediate or high Gleason scores. Am J Clin Pathol. 2002;117(3):471-7. [DOI:10.1309/G6PR-Y774-X738-FG2K] [PMID]
  20. Genega E, Hutchinson B, Reuter V, Gaudin P. Immunophenotype of intermediate and high grade prostatic and urothelial carcinoma. Mod Pathol. 1999;12(suppl 1):87A.
  21. Bassily NH, Vallorosi CJ, Akdas G, Montie JE, Rubin MA. Coordinate expression of cytokeratins 7 and 20 in prostate adenocarcinoma and bladder urothelial carcinoma. Am J Clin Pathol. 2000;113(3):383-8. [DOI:10.1309/G1RA-EU9X-X6VV-3W79] [PMID]
  22. Kunju LP, Mehra R, Snyder M, Shah RB. Prostate-specific antigen, high-molecular-weight cytokeratin (clone 34βE12), and/or p63: an optimal immunohistochemical panel to distinguish poorly differentiated prostate adenocarcinoma from urothelial carcinoma. Am J Clin Pathol. 2006;125(5):675-81. [DOI:10.1309/V1RY91NKX5ARW2Q5] [PMID]
  23. Dariane C, Clairefond S, Péant B, Communal L, Thian Z, Ouellet V, et al. High Keratin-7 Expression in Benign Peri-Tumoral Prostatic Glands Is Predictive of Bone Metastasis Onset and Prostate Cancer-Specific Mortality. Cancers. 2022;14(7):1623. [DOI:10.3390/cancers14071623] [PMID] []
  24. Cheville JC, Dundore PA, Bostwick DG, Lieber MM, Batts KP, Sebo TJ, et al. Transitional cell carcinoma of the prostate: clinicopathologic study of 50 cases. Cancer. 1998;82(4):703-7. [DOI:10.1002/(SICI)1097-0142(19980215)82:43.0.CO;2-1]
  25. Nagle RB, Brawer MK, Kittelson J, Clark V. Phenotypic relationships of prostatic intraepithelial neoplasia to invasive prostatic carcinoma. Am Pathol. 1991;138(1):119-28.
  26. Winter A, Engels S, Goos P, Süykers M-C, Henke R-P, Gerullis H, et al. Detection of CK19 mRNA using one-step nucleic acid amplification (OSNA) in prostate Cancer: preliminary results. J Cancer. 2018;9(24):4611. [DOI:10.7150/jca.26794] [PMID] []
  27. Menz A, Bauer R, Kluth M, von Bargen CM, Gorbokon N, Viehweger F, et al. Diagnostic and prognostic impact of cytokeratin 19 expression analysis in human tumors: A tissue microarray study of 13,172 tumors. Hum Pathol. 2021;115:19-36. [DOI:10.1016/j.humpath.2021.05.012] [PMID]
  28. Mujyambere B, Jayaraj R, Suja S. Cytokeratin 19 (CK19) as a marker for Epithelial Differentiation and Malignant Transformation: Its Clinical relevance in Diagnosis, Prognosis and Treatment response monitoring. Iconic Res Eng J. 2018;2(3):51-61.
  29. Brotherick I, Robson C, Browell D, Shenfine J, White M, Cunliffe W, et al. Cytokeratin expression in breast cancer: phenotypic changes associated with disease progression. Cytometry. 1998;32(4):301-8. [DOI:10.1002/(SICI)1097-0320(19980801)32:43.0.CO;2-K]
  30. Letellier G, Perez M-J, Yacoub M, Levillain P, Cussenot O, Fromont G. Epithelial phenotypes in the developing human prostate. J Histochem Cytochem. 2007;55(9):885-90. [DOI:10.1369/jhc.7A7192.2007] [PMID]