Iranian Journal of Pathology

Significance of Endocan Expression in Various Types of Epithelial Ovarian Tumors

Document Type : Original Research

Authors

Maryam Entezarian 1
Fereshteh Ameli 2
Noraidah Masir 1
Tan Geok Chin 1

1 Department of Pathology, Faculty of Medicine, University Kebangsaan Malaysia, Kuala Lumpur, Malaysia

2 Department of Pathology, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Science, Iran

https://doi.org/10.30699/ijp.2022.540192.2740
Abstract
Background & Objective: Ovarian cancer is associated with the highest mortality rate among gynecologic malignancies. Despite new therapeutic strategies, ovarian cancer still has a high risk of metastasis and mortality. Endocan is a newly identified endothelial cell activation marker, which is responsible for angiogenesis, tumor invasion, and aggressive behavior of tumors. The aim of this study was to assess Endocan expression in different types of ovarian tumors and to identify its relationship with clinicopathologic characteristics of ovarian tumors.
Methods: This cross-sectional study was conducted on 183 tissue samples, including benign, borderline, and malignant ovarian tumors collected from the University Kebangsaan Malaysia Medical Center archive of Pathology during 2005-2015. Mouse monoclonal anti-human Endocan/ESM-1 Clone MEP08 was used at a dilution of 1:400 for immunohistochemical (IHC) staining. All the information was collected by a checklist, and the association between clinicopathological features and high or low levels of Endocan -MVD was evaluated using Pearson chi-square, Fischer's exact, or Monte Carlo tests.
Results: The prevalence of Endocan positivity was significantly higher in malignant compared to borderline and benign ovarian tumors (P<0.001). There was also a significant association between type of tumor and Endocan status in malignant ovarian tumors (P=0.02), indicating that Endocan positivity was more likely in serous malignant ovarian tumors compared to other ovarian tumor types. However, the tumor stage was not significantly associated with Endocan status (P=0.31).
Conclusion: This study showed that Endocan positivity may show the highest prevalence among malignant tumors suggesting that high Endocan expression would be negatively associated with ovarian tumor behavior.

Keywords

Endocan
Endothelial cell-specific molecule-1
Immunohistochemistry
Ovarian
Neoplasm
Tumor

Subjects

  1. Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Pineros M, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. International journal of cancer. 2019;144(8):1941-53. [DOI:10.1002/ijc.31937] [PMID]
  2. Kamat AM HN, Efstathiou JA, Lerner SP, Malmstrom PU, Choi W. Bladder cancer. Lancet (London, England). 2016;388(10061):2796-810. [DOI:10.1016/S0140-6736(16)30512-8]
  3. Pasin E, Josephson DY, Mitra AP, Cote RJ, Stein JP. Superficial bladder cancer: an update on etiology, molecular development, classification, and natural history. Reviews in urology. 2008;10(1):31-43.
  4. Spiess PE, Agarwal N, Bangs R, Boorjian SA, Buyyounouski MK, Clark PE, et al. Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN. 2017;15(10):1240-67. [DOI:10.6004/jnccn.2017.0156] [PMID]
  5. Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nature reviews Cancer. 2012;12(4):278-87. [DOI:10.1038/nrc3236] [PMID]
  6. Cruz E, Kayser V. Monoclonal antibody therapy of solid tumors: clinical limitations and novel strategies to enhance treatment efficacy. Biologics : targets & therapy. 2019;13:33-51. [DOI:10.2147/BTT.S166310] [PMID] [PMCID]
  7. Marrocco I, Romaniello D, Yarden Y. Cancer Immunotherapy: The Dawn of Antibody Cocktails. Methods in molecular biology (Clifton, NJ). 2019;1904:11-51. [DOI:10.1007/978-1-4939-8958-4_2] [PMID]
  8. ZHOU L-l, WANG X-s. Overview of prostate-specific membrane antigen. Anhui Cheml Ind. 2010:01.
  9. Sadaf A, Rahman MZ, Bhattacharjee P, Ahamad MSU, Nasreen S. Significance of Vascular Endothelial Growth Factor Expression in the Bladder Urothelial Carcinoma and Its Association with Tumor Grade and Invasiveness. Iran J Pathol. 2021;16(4):362-9. [DOI:10.30699/ijp.2021.138671.2518] [PMID] [PMCID]
  10. Kouzegaran S, Siroosbakht S, Farsad BF, Rezakhaniha B, Dormanesh B, Behnod V, et al. Elevated IL-17A and IL-22 regulate expression of inducible CD38 and Zap-70 in chronic lymphocytic leukemia. Cytometry B Clin Cytom. 2018;94(1):143-7. [DOI:10.1002/cyto.b.21487] [PMID]
  11. Nykjaer A, Willnow TE. Sortilin: a receptor to regulate neuronal viability and function. Trends Neurosci. 2012;35(4):261-70. [DOI:10.1016/j.tins.2012.01.003] [PMID]
  12. Strong A, Rader DJ. Sortilin as a regulator of lipoprotein metabolism. Curr Atheroscler Rep. 2012;14(3):211-8. [DOI:10.1007/s11883-012-0248-x] [PMID] [PMCID]
  13. Larsen JV, Hermey G, Sorensen ES, Prabakaran T, Christensen EI, Gliemann J, et al. Human sorCS1 binds sortilin and hampers its cellular functions. Biochem J. 2014;457(2):277-88. [DOI:10.1042/BJ20130386] [PMID]
  14. Tanimoto R, Morcavallo A, Terracciano M, Xu SQ, Stefanello M, Buraschi S, et al. Sortilin regulates progranulin action in castration-resistant prostate cancer cells. Endocrinology. 2015;156(1):58-70. [DOI:10.1210/en.2014-1590] [PMID] [PMCID]
  15. Pan X, Zaarur N, Singh M, Morin P, Kandror KV. Sortilin and retromer mediate retrograde transport of Glut4 in 3T3-L1 adipocytes. Mol Biol Cell. 2017;28(12):1667-75. [DOI:10.1091/mbc.e16-11-0777] [PMID] [PMCID]
  16. Petersen CM, Nielsen MS, Nykjaer A, Jacobsen L, Tommerup N, Rasmussen HH, et al. Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatography. J Biol Chem. 1997;272(6):3599-605. [DOI:10.1074/jbc.272.6.3599] [PMID]
  17. Hermey G. The Vps10p-domain receptor family. Cell Mol Life Sci. 2009;66(16):2677-89. [DOI:10.1007/s00018-009-0043-1] [PMID]
  18. Roselli S, Pundavela J, Demont Y, Faulkner S, Keene S, Attia J, et al. Sortilin is associated with breast cancer aggressiveness and contributes to tumor cell adhesion and invasion. Oncotarget. 2015;6(12):10473. [DOI:10.18632/oncotarget.3401] [PMID] [PMCID]
  19. Faulkner S, Jobling P, Rowe CW, Rodrigues Oliveira SM, Roselli S, Thorne RF, et al. Neurotrophin Receptors TrkA, p75(NTR), and Sortilin Are Increased and Targetable in Thyroid Cancer. Am J Pathol. 2018;188(1):229-41. [DOI:10.1016/j.ajpath.2017.09.008] [PMID]
  20. Kim JT, Napier DL, Weiss HL, Lee EY, Townsend Jr CM, Evers BM. Neurotensin receptor 3/sortilin contributes to tumorigenesis of neuroendocrine tumors through augmentation of cell adhesion and migration. Neoplasia. 2018;20(2):175-81. [DOI:10.1016/j.neo.2017.11.012] [PMID] [PMCID]
  21. Ghods R, Ghahremani MH, Darzi M, Mahmoudi AR, Yeganeh O, Bayat AA, et al. Immunohistochemical characterization of novel murine monoclonal antibodies against human placenta-specific 1. Biotechnol Appl Biochem. 2014;61(3):363-9. [DOI:10.1002/bab.1177] [PMID]
  22. Wilson CM, Naves T, Al Akhrass H, Vincent F, Melloni B, Bonnaud F, et al. A new role under sortilin's belt in cancer. Commun Integr Biol. 2016;9(1):e1130192. [DOI:10.1080/19420889.2015.1130192] [PMID] [PMCID]
  23. Ghaemimanesh F, Bayat AA, Babaei S, Ahmadian G, Zarnani AH, Behmanesh M, et al. Production and Characterization of a Novel Monoclonal Antibody Against Human Sortilin. Monoclonal antibodies in immunodiagnosis and immunotherapy. 2015;34(6):390-5. [DOI:10.1089/mab.2015.0042] [PMID] [PMCID]
  24. Bayat AA, Ghods R, Shabani M, Mahmoudi AR, Yeganeh O, Hassannia H, et al. Production and Characterization of Monoclonal Antibodies against Human Prostate Specific Antigen. Avicenna J Med Biotechnol. 2015;7(1):2-7.
  25. Ghaemimanesh F, Ahmadian G, Talebi S, Zarnani AH, Behmanesh M, Hemmati S, et al. The effect of sortilin silencing on ovarian carcinoma cells. Avicenna J Med Biotechnol. 2014;6(3):169-77.
  26. Reyes N, Benedetti I, Bettin A, Rebollo J, Geliebter J. The small leucine rich proteoglycan fibromodulin is overexpressed in human prostate epithelial cancer cell lines in culture and human prostate cancer tissue. Cancer Biomarkers. 2016;16(1):191-202. [DOI:10.3233/CBM-150555] [PMID]
  27. Tsai Y-C, Tsai T-H, Chang C-P, Chen S-F, Lee Y-M, Shyue S-K. Linear correlation between average fluorescence intensity of green fluorescent protein and the multiplicity of infection of recombinant adenovirus. J Biomed Sci. 2015;22(1):1-9. [DOI:10.1186/s12929-015-0137-z] [PMID] [PMCID]
  28. Norouzi S, Norouzi M, Amini M, Amanzadeh A, Nabiuni M, Irian S, et al. Two COX-2 inhibitors induce apoptosis in human erythroleukemia K562cells by modulating NF-κB and FHC pathways. DARU J Pharmal Sci. 2016;24(1):1-9. [DOI:10.1186/s40199-015-0139-0] [PMID] [PMCID]
  29. Batista R, Vinagre N, Meireles S, Vinagre J, Prazeres H, Leao R, et al. Biomarkers for Bladder Cancer Diagnosis and Surveillance: A Comprehensive Review. Diagnostics (Basel, Switzerland). 2020;10(1). [DOI:10.3390/diagnostics10010039] [PMID] [PMCID]
  30. Boggild S, Molgaard S, Glerup S, Nyengaard JR. Spatiotemporal patterns of sortilin and SorCS2 localization during organ development. BMC Cell Biol. 2016;17(1):8. [DOI:10.1186/s12860-016-0085-9] [PMID] [PMCID]
  31. Cabello MJ, Grau L, Franco N, Orenes E, Alvarez M, Blanca A, et al. Multiplexed methylation profiles of tumor suppressor genes in bladder cancer. J Mol Diagn. 2011;13(1):29-40. [DOI:10.1016/j.jmoldx.2010.11.008] [PMID] [PMCID]
  32. Yang W, Wu P-f, Ma J-x, Liao M-j, Wang X-h, Xu L-s, et al. Sortilin promotes glioblastoma invasion and mesenchymal transition through GSK-3β/β-catenin/twist pathway. Cell Death Dis. 2019;10(3):1-15. [DOI:10.1038/s41419-019-1449-9] [PMID] [PMCID]
  33. Kim T, Hempstead BL. NRH2 is a trafficking switch to regulate sortilin localization and permit proneurotrophin‐induced cell death. EMBO J. 2009;28(11):1612-23. [DOI:10.1038/emboj.2009.118] [PMID] [PMCID]
  34. Strong A, Patel K, Rader DJ. Sortilin and lipoprotein metabolism: making sense out of complexity. Curr Opin Lipidol. 2014;25(5):350-7. [DOI:10.1097/MOL.0000000000000110] [PMID] [PMCID]
  35. Demont Y, Corbet C, Page A, Ataman-Önal Y, Choquet-Kastylevsky G, Fliniaux I, et al. Pro-nerve growth factor induces autocrine stimulation of breast cancer cell invasion through tropomyosin-related kinase A (TrkA) and sortilin protein. J Bioll Chem. 2012;287(3):1923-31. [DOI:10.1074/jbc.M110.211714] [PMID] [PMCID]
  36. Rhost S, Hughes E, Harrison H, Rafnsdottir S, Jacobsson H, Gregersson P, et al. Sortilin inhibition limits secretion-induced progranulin-dependent breast cancer progression and cancer stem cell expansion. Breast cancer research : BCR. 2018;20(1):137. [DOI:10.1186/s13058-018-1060-5] [PMID] [PMCID]
  37. Hemmati S, Zarnani AH, Mahmoudi AR, Sadeghi MR, Soltanghoraee H, Akhondi MM, et al. Ectopic Expression of Sortilin 1 (NTR-3) in Patients with Ovarian Carcinoma. Avicenna J Med Biotechnol. 2009;1(2):125-31.
  38. Akil H, Perraud A, Melin C, Jauberteau MO, Mathonnet M. Fine-tuning roles of endogenous brain-derived neurotrophic factor, TrkB and sortilin in colorectal cancer cell survival. PLoS One. 2011;6(9):e25097. [DOI:10.1371/journal.pone.0025097] [PMID] [PMCID]
  39. Farahi L, Ghaemimanesh F, Milani S, Razavi SM, Akhondi MM, Rabbani H. Sortilin as a Novel Diagnostic and Therapeutic Biomarker in Chronic Lymphocytic Leukemia. Avicenna J Med Biotechnol. 2019;11(4):270.
  40. Fauchais AL, Lalloue F, Lise MC, Boumediene A, Preud'homme JL, Vidal E, et al. Role of endogenous brain-derived neurotrophic factor and sortilin in B cell survival. J Immunol. 2008;181(5):3027-38. [DOI:10.4049/jimmunol.181.5.3027] [PMID]
  41. Ludwig DL, Pereira DS, Zhu Z, Hicklin DJ, Bohlen P. Monoclonal antibody therapeutics and apoptosis. Oncogene. 2003;22(56):9097-106. [DOI:10.1038/sj.onc.1207104] [PMID]
  42. Nguyen C, Pandey S. Exploiting Mitochondrial Vulnerabilities to Trigger Apoptosis Selectively in Cancer Cells. Cancers (Basel). 2019;11(7):916. [DOI:10.3390/cancers11070916] [PMID] [PMCID]
  43. Dal Farra C, Sarret P, Navarro V, Botto JM, Mazella J, Vincent JP. Involvement of the neurotensin receptor subtype NTR3 in the growth effect of neurotensin on cancer cell lines. International journal of cancer. 2001;92(4):503-9. [DOI:10.1002/ijc.1225] [PMID]
  44. Massa F, Tormo A, Beraud-Dufour S, Coppola T, Mazella J. Neurotensin-induced Erk1/2 phosphorylation and growth of human colonic cancer cells are independent from growth factors receptors activation. Biochem Biophys Res Commun. 2011;414(1):118-22. [DOI:10.1016/j.bbrc.2011.09.034] [PMID]
  45. Martin S, Vincent JP, Mazella J. Involvement of the neurotensin receptor-3 in the neurotensin-induced migration of human microglia. J Neurosci. 2003;23(4):1198-205. [DOI:10.1523/JNEUROSCI.23-04-01198.2003] [PMID] [PMCID]
  46. Lévêque R, Corbet C, Aubert L, Guilbert M, Lagadec C, Adriaenssens E, et al. ProNGF increases breast tumor aggressiveness through functional association of TrkA with EphA2. Cancer Lett. 2019;449:196-206. [DOI:10.1016/j.canlet.2019.02.019] [PMID]
  47. Serrero G. Autocrine growth factor revisited: PC-cell-derived growth factor (progranulin), a critical player in breast cancer tumorigenesis. Biochem Biophys Res Commun. 2003;308(3):409-13. [DOI:10.1016/S0006-291X(03)01452-9]
Iranian Journal of Pathology
Volume 17, Issue 2
Spring 2022
Pages 202-209

  • Receive Date 02 October 2021
  • Revise Date 30 November 2021
  • Accept Date 30 November 2021

Home

Guide for Authors

Submit Manuscript

Contact Us