Evaluation of CD133 and CD56/NCAM expression in Wilms tumor and their association with prognostic factors

Document Type : Original Article

Authors

Department of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): To validate certain markers for cancer stem cell populations and their clinical importance in Wilms tumor (WT)
Materials and Methods: Immunohistochemical study for CD133 and CD56/NCAM was performed on forty-six cases of WT that were diagnosed between 1999 and 2015, and the association of these markers with survival and prognostic factors was analyzed.
Results: Thirty-four (73.9%) of WTs were positive for CD133 and thirty-nine (84.8%) were positive for CD56/NCAM. A significant positive correlation between CD133 and CD56/NCAM expression and the National Wilms Tumor Stage (NWTS) and death was found. Moreover, overall survival time was significantly correlated with CD133 and CD56/NCAM H-score, NWTS stage, and death.
Conclusion: It seems that CD133 and CD56/NCAM expressions can be used as strong prognostic parameters for the survival of patients with WT and can be used to predict WT patients’ stage. Moreover, their targeted therapies can abolish cancer stem cells in children with recurrent tumors.

Keywords


1. Rich JN. Cancer stem cells: understanding tumor hierarchy and heterogeneity. Medicine 2016;95(Suppl).
2. Pode‐Shakked N, Shukrun R, Mark‐Danieli M, Tsvetkov P, Bahar S, Pri‐Chen S, et al. The isolation and characterization of renal cancer initiating cells from human Wilms’ tumour xenografts unveils new therapeutic targets. EMBO Mol Med 2013;5:18-37.
3. Sternberg’s diagnostic surgical pathology. 6th ed Philadelphia: Wolters Kluwer, 2015.
4. Stocker J. Pediatric pathology: Wolters Kluwer Health 2010.
5. Ali A, Diaz R, Shu H, Paulino A, Esiashvili N. A Surveillance, Epidemiology and End Results (SEER) program comparison of adult and pediatric Wilms’ tumor. Cancer 2012;118:2541-2551.
6. Zhang H, Li S. Research progression of CD133 as a marker of cancer stem cells. Chin J Cancer 2010;29:243-247.
7. Friedman G, Yancey Gillespie G. Cancer stem cells and pediatric solid tumors. Cancers 2011;3:298-318.
8. Kim K, Ihm H, Ro J, Cho Y. High-level expression of stem cell marker CD133 in clear cell renal cell carcinoma with favorable prognosis. Oncol Lett 2011;2:1095-1100.
9. Brugnoli F, Grassilli S, Al-Qassab Y, Capitani S, Bertagnolo V. CD133 in breast cancer cells: more than a stem cell marker. J Oncol 2019;2019:7512632.
10.    Salnikov A, Gladkich J, Moldenhauer G, Volm M, Mattern J, Herr I. CD133 is indicative for a resistance phenotype but does not represent a prognostic marker for survival of non‐small cell lung cancer patients. Int J Cancer 2010;126:950-895.
11.    Yap LW, Brok J, Pritchard-Jones K. Role of CD56 in normal kidney development and Wilms tumorigenesis. Fetal Pediatr Pathol 2017; 36:62-75.
12.    Jafarian AH, Gharib M, Roshan NM, Sherafatnia S, Omidi AA, Bagheri S. The diagnostic value of TTF-1, P63, HMWK, CK7, and CD56 immunostaining in the classification of lung Carcinoma. Iran J Pathol 2017;12:195-201.
13.    Lambert J, O’Leary J, Whiteman K, Goldmacher V. Targeting CD56 (CD56/NCAM)-Expressing Neoplasms with Lorvotuzumab Mertansine. Antibody-Drug Conjugates and Immunotoxins: Springer 2013. p. 273-293.
14.    Masarova L, Kantarjian H, Garcia-Mannero G, Ravandi F, Sharma P, Daver N. Harnessing the immune system against leukemia: monoclonal antibodies and checkpoint strategies for AML. Adv Exp Med Biol 2017;995:73-95.
15.    Mehrazma M, Madjd Z, Kalantari E, Panahi M, Hendi A, Shariftabrizi A. Expression of stem cell markers, CD133 and CD44, in pediatric solid tumors: a study using tissue microarray. Fetal Pediatr Pathol 2013;32:192-204.
16.    Rosai J, Ackerman L. surgical pathology: Elsevier 2018.
17.    Ehrlich P, Ritchey M, Hamilton T, Haase G, Ou S, Breslow N, et al. Quality assessment for Wilms’ tumor: a report from the National Wilms’ Tumor Study-5. J Pediatr Surg 2005;40:208-213.
18.    Pradhan T, Padmanabhan K, Prasad M, Chandramohan K, Nair SA. Augmented CD133 expression in distal margin correlates with poor prognosis in colorectal cancer. J Cell  Mol Med 2019;23:3984-3994.
19.    Yu GF, Lin X, Luo RC, Fang WY. Nuclear CD133 expression predicts poor prognosis for hepatocellular carcinoma. Int J Cli Exp Pathol 2018;11:2092-2099.
20.    Zhong ZY, Shi BJ, Zhou H, Wang WB. CD133 expression and MYCN amplification induce chemoresistance and reduce average survival time in pediatric neuroblastoma. J Int Med Res 2018;46:1209-1220.
21.    Zeppernick F, Ahmadi R, Campos B, Dictus C, Helmke B, Becker N, et al. Stem cell marker CD133 affects clinical outcome in glioma patients. Clin Cancer Res 2008;14:123-129.
22. Choi D, Lee HW, Hur KY, Kim JJ, Park GS, Jang SH, et al. Cancer stem cell markers CD133 and CD24 correlate with invasiveness and differentiation in colorectal adenocarcinoma. World J Gastroenterol 2009;15:2258-2264.
23.    Ash S, Luria D, Cohen I, Goshen Y, Toledano H, Issakov J, et al. Excellent prognosis in a subset of patients with Ewing sarcoma identified at diagnosis by CD56 using flow cytometry. Clin Cancer Res 2011;17:2900-2907.
24. Tsuchiya A, Kamimura H, Tamura Y, Takamura M, Yamagiwa S, Suda T, et al. Hepatocellular carcinoma with progenitor cell features distinguishable by the hepatic stem/progenitor cell marker CD56/NCAM. Cancer Lett 2011;309:95-103.