Analyze Diet
Journal of equine science2023; 34(2); 37-46; doi: 10.1294/jes.34.37

Immunohistochemical markers for equine granulosa cell tumors: a pilot study.

Abstract: Sex cord-stromal tumors (SCSTs), generally referred to as granulosa cell tumors (GCTs) or granulosa-theca cell tumors (GTCTs) in equids, show complex compositions and variable numbers of hormone-producing cells. These tumors can be difficult to diagnose, especially in early stages. Therefore, we tested a panel of antibodies for vimentin, smooth muscle actin, laminin, Ki-67, E-cadherin, calretinin, moesin, p-ezrin, AMH, and aromatase, markers used for tumor composition and classification, progression, and prognosis in human SCSTs, on an exemplary grapefruit-size equine GCT within the left ovary of a 13-year-old mare with stallion-like behavior and elevated testosterone levels in comparison with normal ovarian tissue. The tumor showed a low proliferation rate and prominent moesin and p-ezrin staining in granulosa cells. E-cadherin, calretinin, aromatase, and AMH are suggested to be potential markers for different cell components of equine SCSTs that can support tumor diagnosis and classification.
Publication Date: 2023-06-12 PubMed ID: 37405069PubMed Central: PMC10315638DOI: 10.1294/jes.34.37Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study examined the use of various antibodies, which are often used for identifying and classifying human sex cord-stromal tumors (SCSTs), to investigate and diagnose similar tumors in horses. The researchers specifically tested these markers on a large SCST—or granulosa cell tumor (GCT)—found in an aged mare, and found several of them to be potentially useful for identifying different components of the tumor.

Research Background and Objectives

  • Equine Sex cord-stromal tumors (SCSTs) are complex structures that often contain variable numbers of hormone-producing cells. They are also known as granulosa cell tumors (GCTs) or granulosa-theca cell tumors (GTCTs) when referring to their existence in equids (horses, donkeys, etc.)
  • These tumors are challenging to diagnose particularly in their early stages, hence the need for effective biochemical markers to aid diagnosis, track disease progression, and predict outcomes.
  • In this pilot study, researchers sought to determine the diagnostic efficiency of several antibodies that are typically used for the identification and classification of human SCTCs. They did this by comparing the levels of these markers in a GCT from a 13-year-old mare with elevated testosterone levels and abnormal behaviour to levels seen in healthy ovarian tissue.

Methods and Findings

  • The panel of antibodies examined in the study included vimentin, smooth muscle actin, laminin, Ki-67, E-cadherin, calretinin, moesin, p-ezrin, AMH, and aromatase. These antibodies were chosen because they are already markers for tumor composition, progression, and prognosis in humans.
  • The equine tumor under investigation was grapefruit-sized and located in the left ovary of the mare. This tumor exhibited a low proliferation rate, indicating slow growth.
  • Results showed prominent staining of moesin and p-ezrin in the granulosa cells of the tumor. The staining of these antibodies signifies their presence and can aid in determining the composition of the tumor.
  • E-cadherin, calretinin, aromatase, and AMH were identified as potentially useful markers for different components of equine SCSTs, suggesting their potential utility in diagnosing and classifying equine SCTCs.

Conclusion and Implications

  • The research provides preliminary evidence suggesting that certain antibodies used to study SCSTs in humans, namely E-cadherin, calretinin, aromatase, and AMH, might also be effective in identifying and classifying equine SCSTs.
  • These findings could improve the diagnosis and treatment of SCSTs in horses, potentially contributing to better health outcomes for these animals. However, further research is necessitated to validate these findings on a larger scale.
  • Though the study was conducted on equines, given the similarities between SCSTs in humans and horses, these findings could indirectly hint at a potential avenue for improving understanding, diagnosis, and treatment in humans as well.

Cite This Article

APA
Dolin A, Schweiger P, Waselau M, Egerbacher M, Walter I. (2023). Immunohistochemical markers for equine granulosa cell tumors: a pilot study. J Equine Sci, 34(2), 37-46. https://doi.org/10.1294/jes.34.37

Publication

ISSN: 1340-3516
NlmUniqueID: 9503751
Country: Japan
Language: English
Volume: 34
Issue: 2
Pages: 37-46

Researcher Affiliations

Dolin, Aurelia
  • Veterinary Practice Tierdoc, 6233 Kramsach, Austria.
Schweiger, Peter
  • Veterinary Practice Tierdoc, 6233 Kramsach, Austria.
Waselau, Martin
  • Equine Hospital Aschheim, Equine Diagnostic Center Munich, 85609 Munich, Germany.
Egerbacher, Monika
  • Administrative Unit Veterinary Medicine, UMIT TIROL-Private University for Health Sciences, Medical Informatics and Technology GmbH, 6060 Hall in Tirol, Austria.
Walter, Ingrid
  • Department of Pathobiology, Institute of Morphology, Vetmeduni Vienna, 1210 Vienna, Austria.

References

This article includes 47 references
  1. Akhter S, Islam N, Kabir E, Begum S, Gaffar T, Khan AA. Expression of Ki-67 in ovarian tumors and its correlation with type, grade and stage.. J. Histopathol. Cytopathol. 2019;3:15–26.
  2. Ibrahim ALA. Studies to characterize ovarian tumours in the mare.. PhD Thesis, University of Glasgow 2019.
  3. Almadhidi J, Seralini GE, Fresnel J, Silberzahn P, Gaillard JL. Immunohistochemical localization of cytochrome P450 aromatase in equine gonads.. J Histochem Cytochem 1995 Jun;43(6):571-7.
    pubmed: 7769228doi: 10.1177/43.6.7769228google scholar: lookup
  4. Neto AC, Ball BA, Browne P, Conley AJ. Cellular localization of androgen synthesis in equine granulosa-theca cell tumors: immunohistochemical expression of 17alpha-hydroxylase/17,20-lyase cytochrome P450.. Theriogenology 2010 Aug;74(3):393-401.
  5. Balan RA, Căruntu ID, Giuşcă SE, Lozneanu L, Păvăleanu I, Socolov RV, Miron L, Marinca MV, Amălinei C. Immunohistochemical significance of ER alpha, inhibin A, calretinin, and Ki67 expression in granulosa cell ovarian tumors.. Rom J Morphol Embryol 2017;58(3):753-760.
    pubmed: 29250651
  6. Ball BA, Conley AJ, MacLaughlin DT, Grundy SA, Sabeur K, Liu IK. Expression of anti-Müllerian hormone (AMH) in equine granulosa-cell tumors and in normal equine ovaries.. Theriogenology 2008 Oct 1;70(6):968-77.
  7. Ball BA, Almeida J, Conley AJ. Determination of serum anti-Müllerian hormone concentrations for the diagnosis of granulosa-cell tumours in mares.. Equine Vet J 2013 Mar;45(2):199-203.
  8. Bosu WT, Van Camp SC, Miller RB, Owen RR. Ovarian disorders: clinical and morphological observations in 30 mares.. Can Vet J 1982 Jan;23(1):6-14.
    pmc: PMC1790073pubmed: 7066859
  9. Crabtree J. Review of seven cases of granulosa cell tumour of the equine ovary.. Vet Rec 2011 Sep 3;169(10):251.
    pubmed: 21832000doi: 10.1136/vr.d4635google scholar: lookup
  10. Cao QJ, Jones JG, Li M. Expression of calretinin in human ovary, testis, and ovarian sex cord-stromal tumors.. Int J Gynecol Pathol 2001 Oct;20(4):346-52.
  11. Castillo JM, Tse MPY, Dockweiler JC, Cheong SH, de Amorim MD. Bilateral granulosa cell tumor in a cycling mare.. Can Vet J 2019 May;60(5):480-484.
    pmc: PMC6463771pubmed: 31080259
  12. Chen VW, Ruiz B, Killeen JL, Coté TR, Wu XC, Correa CN. Pathology and classification of ovarian tumors.. Cancer 2003 May 15;97(10 Suppl):2631-42.
    pubmed: 12733128doi: 10.1002/cncr.11345google scholar: lookup
  13. Chen Z, Fadiel A, Feng Y, Ohtani K, Rutherford T, Naftolin F. Ovarian epithelial carcinoma tyrosine phosphorylation, cell proliferation, and ezrin translocation are stimulated by interleukin 1alpha and epidermal growth factor.. Cancer 2001 Dec 15;92(12):3068-75.
  14. Chi H, Huang N, Liang H, Li R, Liu C, Qiao J. Abnormal Elevation of Anti-Mullerian Hormone and Androgen Levels Presenting as Granulosa Cell Tumor.. Front Oncol 2021;11:641166.
    pmc: PMC8019939pubmed: 33828986doi: 10.3389/fonc.2021.641166google scholar: lookup
  15. Choudhury M, Goyal S, Pujani M. A cytohistological study of Ki-67 expression in ovarian tumors.. Indian J Pathol Microbiol 2011 Jan-Mar;54(1):21-4.
    pubmed: 21393871doi: 10.4103/0377-4929.77318google scholar: lookup
  16. Clucas J, Valderrama F. ERM proteins in cancer progression.. J Cell Sci 2014 Jan 15;127(Pt 2):267-75.
    pubmed: 24421310doi: 10.1242/jcs.133108google scholar: lookup
  17. Matos ACHDS, Consalter A, Dos Santos Batista BP, Fonseca ABM, Ferreira AMR, Leite JDS. Immunohistochemical expression of HER - 2 and Ki - 67 in granulosa cell tumor in bitches.. Reprod Domest Anim 2021 Apr;56(4):667-672.
    pubmed: 33527594doi: 10.1111/rda.13903google scholar: lookup
  18. Deavers MT, Malpica A, Liu J, Broaddus R, Silva EG. Ovarian sex cord-stromal tumors: an immunohistochemical study including a comparison of calretinin and inhibin.. Mod Pathol 2003 Jun;16(6):584-90.
  19. Devick IF, Leise BS, McCue PM, Rao S, Hendrickson DA. Ovarian histopathology, pre- and post-operative endocrinological analysis and behavior alterations in 27 mares undergoing bilateral standing laparoscopic ovariectomy.. Can Vet J 2020 Feb;61(2):181-186.
    pmc: PMC6973214pubmed: 32020939
  20. Diel de Amorim M, Nairn D, Manning S, Dedden I, Ripley E, Nielsen K, Card C. Evaluation of diagnostic utility, safety considerations, and effect on fertility of transvaginal ultrasound-guided ovarian biopsy in mares.. Theriogenology 2016 Apr 1;85(6):1030-6.
  21. Durkes A, Garner M, Juan-Sallés C, Ramos-Vara J. Immunohistochemical characterization of nonhuman primate ovarian sex cord-stromal tumors.. Vet Pathol 2012 Sep;49(5):834-8.
    pubmed: 22273575doi: 10.1177/0300985811432345google scholar: lookup
  22. Ellenberger C, Bartmann CP, Hoppen HO, Kratzsch J, Aupperle H, Klug E, Schoon D, Schoon HA. Histomorphological and immunohistochemical characterization of equine granulosa cell tumours.. J Comp Pathol 2007 Feb-Apr;136(2-3):167-76.
    pubmed: 17416235doi: 10.1016/j.jcpa.2007.01.011google scholar: lookup
  23. Gift LJ, Gaughan EM, Schoning P. Metastatic granulosa cell tumor in a mare.. J Am Vet Med Assoc 1992 May 15;200(10):1525-6.
    pubmed: 1612993
  24. Goto A, Tagami M, Kato F, Suzuki T, Yamaga T, Murase H, Sato F, Tsogtgerel M, Niikura T, Moriyama T, Chiba A, Watanabe KI, Tsuzuki N, Nambo Y. Equine nonneoplastic abnormal ovary in a draft mare with high serum anti-Müllerian hormone: a case study.. J Equine Sci 2021 Dec;32(4):147-151.
    pmc: PMC8731685pubmed: 35023993doi: 10.1294/jes.32.147google scholar: lookup
  25. Hlavaty J, Wolfesberger B, Hauck M, Obermayer-Pietsch B, Fuchs-Baumgartinger A, Miller I, Walter I. Ezrin and moesin expression in canine and feline osteosarcoma.. Histol Histopathol 2017 Aug;32(8):805-816.
    pubmed: 27900754doi: 10.14670/hh-11-848google scholar: lookup
  26. Hoque S, Derar RI, Senba H, Osawa T, Kano K, Taya K, Miyake Y. Localization of inhibin alpha-, betaA- and betaB-subunits and aromatase in ovarian follicles with granulosa theca cell tumor (GTCT) in 6 mares.. J Vet Med Sci 2003 Jun;65(6):713-7.
    pubmed: 12867732doi: 10.1292/jvms.65.713google scholar: lookup
  27. Kanthan R, Senger JL, Kanthan S. The multifaceted granulosa cell tumours-myths and realities: a review.. ISRN Obstet Gynecol 2012;2012:878635.
    pmc: PMC3449135pubmed: 23008780doi: 10.5402/2012/878635google scholar: lookup
  28. Kaszak I, Witkowska-Piłaszewicz O, Niewiadomska Z, Dworecka-Kaszak B, Ngosa Toka F, Jurka P. Role of Cadherins in Cancer-A Review.. Int J Mol Sci 2020 Oct 15;21(20).
    pmc: PMC7589192pubmed: 33076339doi: 10.3390/ijms21207624google scholar: lookup
  29. Kishore R, Qin G, Luedemann C, Bord E, Hanley A, Silver M, Gavin M, Yoon YS, Goukassian D, Losordo DW. The cytoskeletal protein ezrin regulates EC proliferation and angiogenesis via TNF-alpha-induced transcriptional repression of cyclin A.. J Clin Invest 2005 Jul;115(7):1785-96.
    pmc: PMC1150283pubmed: 15965500doi: 10.1172/jci22849google scholar: lookup
  30. Kitahara G, Nambo Y, El-Sheikh Ali H, Kajisa M, Tani M, Nibe K, Kamimura S. Anti-Müllerian hormone profiles as a novel biomarker to diagnose granulosa-theca cell tumors in cattle.. J Reprod Dev 2012;58(1):98-104.
    pubmed: 22052009doi: 10.1262/jrd.11-101tgoogle scholar: lookup
  31. Köbel M, Gradhand E, Zeng K, Schmitt WD, Kriese K, Lantzsch T, Wolters M, Dittmer J, Strauss HG, Thomssen C, Hauptmann S. Ezrin promotes ovarian carcinoma cell invasion and its retained expression predicts poor prognosis in ovarian carcinoma.. Int J Gynecol Pathol 2006 Apr;25(2):121-30.
  32. MacLachlan NJ. Ovarian disorders in domestic animals.. Environ Health Perspect 1987 Aug;73:27-33.
    pmc: PMC1474553pubmed: 3665869doi: 10.1289/ehp.877327google scholar: lookup
  33. McCue PM, Roser JF, Munro CJ, Liu IK, Lasley BL. Granulosa cell tumors of the equine ovary.. Vet Clin North Am Equine Pract 2006 Dec;22(3):799-817.
    pubmed: 17129804doi: 10.1016/j.cveq.2006.08.008google scholar: lookup
  34. Movahedi-Lankarani S, Kurman RJ. Calretinin, a more sensitive but less specific marker than alpha-inhibin for ovarian sex cord-stromal neoplasms: an immunohistochemical study of 215 cases.. Am J Surg Pathol 2002 Nov;26(11):1477-83.
  35. Patnaik AK, Greenlee PG. Canine ovarian neoplasms: a clinicopathologic study of 71 cases, including histology of 12 granulosa cell tumors.. Vet Pathol 1987 Nov;24(6):509-14.
    pubmed: 2842918doi: 10.1177/030098588702400607google scholar: lookup
  36. Patrick DJ, Kiupel M, Gerber V, Carr EA. Malignant granulosa-theca cell tumor in a two-year-old Miniature Horse.. J Vet Diagn Invest 2003 Jan;15(1):60-3.
    pubmed: 12580299doi: 10.1177/104063870301500114google scholar: lookup
  37. Renaudin CD, Kelleman AA, Keel K, McCracken JL, Ball BA, Ferris RA, McCue PM, Dujovne G, Conley AJ. Equine granulosa cell tumours among other ovarian conditions: Diagnostic challenges.. Equine Vet J 2021 Jan;53(1):60-70.
    pubmed: 32391939doi: 10.1111/evj.13279google scholar: lookup
  38. Ryan PL, Valentine AF, Bagnell CA. Expression of epithelial cadherin in the developing and adult pig ovary.. Biol Reprod 1996 Nov;55(5):1091-7.
    pubmed: 8902222doi: 10.1095/biolreprod55.5.1091google scholar: lookup
  39. Schlafer DH, Foster RA. Female Genital System. Neoplastic conditions of the ovary.. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals 2015;Vol. 3, 6th ed., pp. 375–378.
  40. Sherlock CE, Lott-Ellis K, Bergren A, Withers JM, Fews D, Mair TS. Granulosa cell tumours in the mare: A review of 52 cases.. Equine Vet. Educ. 2016;28:75–82.
  41. Song J, Fadiel A, Edusa V, Chen Z, So J, Sakamoto H, Fishman DA, Naftolin F. Estradiol-induced ezrin overexpression in ovarian cancer: a new signaling domain for estrogen.. Cancer Lett 2005 Mar 18;220(1):57-65.
    pubmed: 15737688doi: 10.1016/j.canlet.2004.04.024google scholar: lookup
  42. Stabenfeldt GH, Hughes JP, Kennedy PC, Meagher DM, Neely DP. Clinical findings, pathological changes and endocrinological secretory patterns in mares with ovarian tumours.. J Reprod Fertil Suppl 1979;(27):277-85.
    pubmed: 289801
  43. Sundfeldt K, Piontkewitz Y, Billig H, Hedin L. E-cadherin-catenin complex in the rat ovary: cell-specific expression during folliculogenesis and luteal formation.. J Reprod Fertil 2000 Mar;118(2):375-85.
    pubmed: 10864803doi: 10.1530/jrf.0.1180375google scholar: lookup
  44. Teh APP, Kitahara G, Izzati UZ, Mori K, Fuke N, Hirai T, Yamaguchi R. Immunohistochemical and Morphological Features of Bovine Granulosa Cell Tumours in Relation to Growth Pattern and Folliculogenesis.. J Comp Pathol 2021 Aug;187:40-51.
    pubmed: 34503653doi: 10.1016/j.jcpa.2021.06.008google scholar: lookup
  45. Tsogtgerel M, Tagami M, Watanabe K, Murase H, Hirosawa Y, Kobayashi Y, Nambo Y. Case report: The case of a 17 kg ovarian granulosa cell tumor in a Breton draft mare.. J Equine Sci 2021 Jun;32(2):67-72.
    pmc: PMC8240524pubmed: 34220274doi: 10.1294/jes.32.67google scholar: lookup
  46. Watson ED, Thomson SR. Immunolocalization of aromatase P-450 in ovarian tissue from pregnant and nonpregnant mares and in ovarian tumours.. J Reprod Fertil 1996 Nov;108(2):239-44.
    pubmed: 9038782doi: 10.1530/jrf.0.1080239google scholar: lookup
  47. Yoshida G, Tsunoda N, Miyake YI, Shafiqul HMD, Osawa T, Nagamine N, Taniyma H, Nambo Y, Watanabe G, Taya K. Endocrinological studies of mares with granulosa-theca cell tumor.. J. Equine Sci. 2000;11:35–43.

Citations

This article has been cited 0 times.