Vol 57, No 3 (2019)
Original paper
Published online: 2019-09-12

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Nucleolin and nucleophosmin expression in seminomas and non-seminomatous testicular tumors

Marek Masiuk12, Magdalena Lewandowska1, Leszek Teresinski2, Ewa Dobak1, Elzbieta Urasinska1
Pubmed: 31513277
Folia Histochem Cytobiol 2019;57(3):139-145.

Abstract

Introduction. Testicular tumors are heterogeneous group of neoplasms divided mainly into two types: seminomas and non-seminomas. Nucleolin (NCL) and nucleophosmin (NPM) are abundant nucleolar proteins involved in many physiologic and pathologic processes including cancer. Their overexpression was found in many tumors but it was not studied in testicular cancer.

Material and methods. The study was performed on tissue microarrays of 19 seminomas, 21 embryonal carcinomas and 11 yolk sac tumors. The expression of NCL and NPM was detected with monoclonal antibodies and visualized with EnVision FLEX/HRP technique. Immunohistochemical reactions were measured with Aperio ImageScope Software and analyzed as means of percentages of all immunopositive cells in three groups of reaction intensity, i.e. 3+, 2+, and 1+ as well as of H-score.

Results. Seminomas showed higher expression of nucleolin indicated by higher H-score and higher percentage of positive cells than non-seminomas. The differences in subpopulations of NCL-positive cells were also found. Embryonal carcinomas and yolk sac tumors showed lower expression of NCL than seminomas indicated by H-score. The percentage of NCL-positive cells did not differ between embryonal carcinomas and seminomas while there were significant differences in subpopulations of cells. The percentage of NCL-positive cells in yolk sac tumors was lower than in seminomas. The results show different heterogeneity of subpopulations of NCL-positive cells in embryonal carcinomas and yolk sac tumors compared to seminomas. The analysis of nucleolin expression in embryonal carcinomas and yolk sac tumors showed no differences between these two tumor types. No differences in nucleophosmin expression between seminomas and non-seminomas were found.

Conclusions. The differences in the expression of nucleolin between two groups of germ cell testicular tumors found in the current study indicate a new aspect of biology of these neoplasms and require further studies on the role of nucleolin in germ cell tumorigenesis.

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References

  1. Bray F, Richiardi L, Ekbom A, et al. Trends in testicular cancer incidence and mortality in 22 European countries: continuing increases in incidence and declines in mortality. Int J Cancer. 2006; 118(12): 3099–3111.
  2. Elzinga-Tinke JE, Dohle GR, Looijenga LHj. Etiology and early pathogenesis of malignant testicular germ cell tumors: towards possibilities for preinvasive diagnosis. Asian J Androl. 2015; 17(3): 381–393.
  3. Young RH. Testicular tumors--some new and a few perennial problems. Arch Pathol Lab Med. 2008; 132(4): 548–564.
  4. Ulbright TM. Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues. Mod Pathol. 2005; 18 Suppl 2: S61–S79.
  5. Looijenga LHJ, Stoop H, de Leeuw HP, et al. POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors. Cancer Res. 2003; 63(9): 2244–2250.
  6. Mitchell RT, Camacho-Moll M, Macdonald J, et al. Intratubular germ cell neoplasia of the human testis: heterogeneous protein expression and relation to invasive potential. Mod Pathol. 2014; 27(9): 1255–1266.
  7. Moch H., Humphrey PA, Ulbright TM, Reuter VE (ed.). (2016). WHO Classification of Tumours of the Urinary System and Male Genital Organs. 4th Edition. International Agency for Research on Cancer, Lyon, pp 190-193.
  8. Honecker F, Stoop H, Mayer F, et al. Germ cell lineage differentiation in non-seminomatous germ cell tumours. J Pathol. 2006; 208(3): 395–400.
  9. de Jong J, Stoop H, Gillis AJM, et al. Differential expression of SOX17 and SOX2 in germ cells and stem cells has biological and clinical implications. J Pathol. 2008; 215(1): 21–30.
  10. Looijenga LHJ. Human testicular (non)seminomatous germ cell tumours: the clinical implications of recent pathobiological insights. J Pathol. 2009; 218(2): 146–162.
  11. Ma N, Matsunaga S, Takata H, et al. Nucleolin functions in nucleolus formation and chromosome congression. J Cell Sci. 2007; 120(Pt 12): 2091–2105.
  12. Abdelmohsen K, Gorospe M. RNA-binding protein nucleolin in disease. RNA Biol. 2012; 9(6): 799–808.
  13. Tajrishi MM, Tuteja R, Tuteja N. Nucleolin: The most abundant multifunctional phosphoprotein of nucleolus. Commun Integr Biol. 2011; 4(3): 267–275.
  14. Masiuk M, Urasinska E, Domagala W. Simultaneous measurement of nucleolin and estrogen receptor in breast cancer cells by laser scanning cytometry. Anticancer Res. 2004;24:963-966. Indexed in Pubmed. ; 15161050.
  15. Šašinková M, Holoubek A, Otevřelová P, et al. AML-associated mutation of nucleophosmin compromises its interaction with nucleolin. Int J Biochem Cell Biol. 2018; 103: 65–73.
  16. Chen S, He H, Wang Y, et al. Poor prognosis of nucleophosmin overexpression in solid tumors: a meta-analysis. BMC Cancer. 2018; 18(1): 838.
  17. Masiuk M. Expression and intranuclear distribution of nucleolin in estrogen receptor-negative and estrogen receptor-positive breast cancers in women measured by laser scanning cytometry]. Ann Acad Med Stetin. 2006;52:23-32. In Polish. Indexed in Pubmed. ; 17633394.
  18. Meng FJ, Giwercman A, Skakkebaek NE. Investigation of carcinoma in situ cells of testis by quantification of argyrophilic nucleolar organizer region associated proteins (AgNORs). J Pathol. 1996; 180(2): 206–213.
  19. Ohyama C, Ito A, Tokuyama S, et al. [Clinical significance of proliferating cell nuclear antigen (PCNA) and argyrophilic nucleolar organizer region (AgNOR) in testicular tumors]. Nihon Hinyokika Gakkai Zasshi. 1995; 86(10): 1543–1551.
  20. Xu JY, Lu S, Xu XY, et al. Prognostic significance of nuclear or cytoplasmic nucleolin expression in human non-small cell lung cancer and its relationship with DNA-PKcs. Tumour Biol. 2016; 37(8): 10349–10356.
  21. Shen H, Shih J, Hollern DP, et al. Cancer Genome Atlas Research Network. Integrated Molecular Characterization of Testicular Germ Cell Tumors. Cell Rep. 2018; 23(11): 3392–3406.
  22. Ko CY, Lin CH, Chuang JY, et al. MDM2 Degrades Deacetylated Nucleolin Through Ubiquitination to Promote Glioma Stem-Like Cell Enrichment for Chemotherapeutic Resistance. Mol Neurobiol. 2018; 55(4): 3211–3223.
  23. Wu YL, Dudognon C, Nguyen E, et al. Immunodetection of human telomerase reverse-transcriptase (hTERT) re-appraised: nucleolin and telomerase cross paths. J Cell Sci. 2006; 119(Pt 13): 2797–2806.
  24. Khurts S, Masutomi K, Delgermaa L, et al. Nucleolin interacts with telomerase. J Biol Chem. 2004; 279(49): 51508–51515.
  25. Schrader M, Burger A, Müller M, et al. The differentiation status of primary gonadal germ cell tumors correlates inversely with telomerase activity and the expression level of the gene encoding the catalytic subunit of telomerase. BMC Cancer. 2002; 2(1).
  26. Turnbull C, Rapley EA, Seal S, et al. UK Testicular Cancer Collaboration. Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer. Nat Genet. 2010; 42(7): 604–607.
  27. Pianta A, Puppin C, Franzoni A, et al. Nucleophosmin is overexpressed in thyroid tumors. Biochem Biophys Res Commun. 2010; 397(3): 499–504.
  28. Sari A, Calli A, Altinboga AA, et al. Nucleophosmin expression in renal cell carcinoma and oncocytoma. APMIS. 2012; 120(3): 187–194.