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Vimentin, osteocalcin and osteonectin expression in canine primary bone tumors: diagnostic and prognostic implications

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Abstract

Canine primary bone tumors have a plastic radiographic image, demanding histopathological confirmation. Bone tumors are characterized by the type and amount of extracellular matrix produced what cannot be easily recognized, especially in biopsy samples. Identifying cellular markers that could aid diagnosis has supported various studies in oncological pathology. This study aimed to evaluate 22 canine primary bone neoplasms, establishing their histopathological diagnosis and evaluated vimentin, osteonectin and osteocalcin expression and their implication in diagnosis and prognosis. There were 12 productive osteoblastic osteosarcomas, six minimally productive osteoblastic osteosarcoma, two chondrosarcomas, one fibrosarcoma and one hemangiosarcoma. Immunostaining was cytoplasmatic in all cases, with average percentage of 87.9% for vimentin, 98.0% for osteonectin and 99.9% for osteocalcin. In this last case, only osteosarcomas were considered. Intensity was higher in vimentin labeling (+++), followed by osteonectin (++) and osteocalcin (+). One osteosarcoma showed negative immunostaining for vimentin and of samples submitted to anti-osteocalcin immunostaining, three osteosarcomas and one fibrosarcoma had negative staining. Besides identifying mesenchymal origin, vimentin elevated expression in canine bone tumors can be related to epithelial–mesenchymal transition, leading to more aggressive tumoral phenotypes and metastasis development. Similarly, high osteonectin expression is implicated in neoplastic cell invasion and is also related to metastasis spread. Decreased osteocalcin expression was found in some osteosarcoma samples and can be related to poor prognosis, as in human osteosarcomas. Our findings suggest that vimentin, osteonectin and osteocalcin not only aid diagnosis but can be related to prognosis in canine primary bone tumors, especially osteosarcomas and its osteoblastic subtype.

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References

  1. Ehrhart NP, Ryan SD, Fan TM (2013) Tumors of the skeletal system. In: Withrow SJ, Vail DM, Page RL (eds) Withrow & MacEwen’s small animal clinical oncology. 5th edn. Elsevier Saunders Company, Missouri, pp 463–503

    Chapter  Google Scholar 

  2. Sabattini S, Renzi A, Buracco P, Defourny S, Garnier-Moiroux M, Capitani O, Bettini G (2017) Comparative assessment of the accuracy of cytological and histologic biopsies in the diagnosis of canine bone lesions. J Vet Intern Med 31:864–871

    Article  CAS  Google Scholar 

  3. Morello E, Martano M, Buracco P (2011) Biology, diagnosis and treatment of canine appendicular osteosarcoma: similarities and differences with human osteosarcoma. Vet J 189:268–277

    Article  Google Scholar 

  4. Simpson S, Dunning MD, De Brot S, Grau-Roma L, Mongan NP, Rutland CS (2017) Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics. Acta Vet Scand 59:71

    Article  Google Scholar 

  5. Fenger JM, London CA, Kisseberth WC (2014) Canine osteosarcoma: a naturally occurring disease to inform pediatric oncology. ILAR J 55:69–85

    Article  CAS  Google Scholar 

  6. Fan TM, Khanna C (2015) Comparative aspects of osteosarcoma pathogenesis in humans and dogs. Vet Sci 2:210–230

    Article  Google Scholar 

  7. Vanel M, Blond L, Vanel D (2013) Imaging of primary bone tumors in veterinary medicine: which differences? Eur J Radiol 82:2129–2139

    Article  Google Scholar 

  8. Redondo A, Bagué S, Bernabeu D, Ortiz-Cruz E, Valverde C, Alvarez R, Martinez-Trufero J, Lopez-Martin JA, Correa R, Cruz J, Lopez-Pousa A, Santos A, Del Muro XG, Martin-Broto J (2017) Malignant bone tumors (other than Ewing’s): clinical practice guidelines for diagnosis, treatment and follow-up by Spanish Group for Research on Sarcomas (GEIS). Cancer Chemother Pharmacol 80:1113–1131

    Article  Google Scholar 

  9. Niu X, Xu H, Inwards CY, Li Y, Ding Y, Letson GD, Bui MM (2015) Primary bone tumors: epidemiologic comparison of 9200 patients treated at Beijing Ji Shui Tan Hospital, Beijing, China, with 10.165 patients at Mayo Clinic, Rochester, Minnesota. Arch Pathol Lab Med 139:1149–1155

    Article  Google Scholar 

  10. Slayter MV, Boosinger TR, Pool RR, Dämmrich K, Misdorp W, Larsen S (1994) Histological classification of bone and joint tumors of domestic animals. Armed Forces Institute of Pathology, Washington, DC

    Google Scholar 

  11. Fletcher CDM, Unni KK, Mertens F (2002) World Health Organization classification of tumours. Pathology and genetics of tumours of soft tissue and bone. International Agency for Research on Cancer, Lyon

    Google Scholar 

  12. Nagamine E, Hirayama K, Matsuda K, Okamoto M, Ohmachi T, Kadosawa T, Taniyama H (2015) Diversity of histologic patterns and expression of cytoskeletal proteins in canine skeletal osteosarcoma. Vet Pathol 52:977–984

    Article  CAS  Google Scholar 

  13. Wehrle-Martinez AS, Dittmer KE, Aberdein D, Thompson KG (2016) Osteocalcin and osteonectin expression in canine osteosarcoma. Vet Pathol 53:781–787

    Article  CAS  Google Scholar 

  14. Mesquita l, Mortier J, Ressel L, Finotello R, Silvestrini P, Piviani M (2017) Neoplastic pleural effusion and intrathoracic metastasis of a scapular osteosarcoma in a dog: a multidisciplinary integrated diagnostic approach. Vet Clin Pathol 46:337–343

    Article  Google Scholar 

  15. Daugaard S, Christensen LH, Hogdall E (2009) Markers aiding the diagnosis of chondroid tumors: an immunohistochemical study including osteonectin, bcl-2, cox-2, actin, calponin, D2-40 (podoplanin), mdm-2, CD117 (c-kit) and YKL-40. APMIS 117:518–525

    Article  CAS  Google Scholar 

  16. El-Badawi ZH, Muhammad EM, Noaman HH (2012) Role of immunohistochemical cyclo-oxygenase-2 (COX-2) and osteocalcin in differentiating between osteoblastomas and osteosarcomas. Malas J Pathol 34:15–23

    Google Scholar 

  17. Lamb S, Reavill D, Wojcieszyn J, Sitinas N (2014) Osteosarcoma of the tibiotarsus with possible pulmonary metastasis in a Ring-necked dove (Streptopelia risoria). J Avian Med Surg 28:50–56

    Article  Google Scholar 

  18. Wijesundera KK, Izawa T, Fujita D, Denda Y, Seto E, Sasai H, Kuwamura M, Yamate J (2013) Spontaneous extraskeletal osteosarcoma in a rabbit (Oryctolagus cuniculus): histopathological and immunohistochemical findings. J Toxicol Pathol 26:309–312

    Article  Google Scholar 

  19. Salyards GW, Blas-Machado U, Mishra S, Harvey SB, Butler AM (2013) Spontaneous osteoblastic osteosarcoma in a Mongolian gerbil (Meriones unguiculatus). Comp Med 63:62–66

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Bord S (2003) Protein localization in wax-embedded and frozen sections of bone using immunhistochemistry. In: Helfrich MH, Ralston SH (eds) Bone research Protocols, 1st edn. Springer, New York, pp 237–247

    Chapter  Google Scholar 

  21. Satelli A, Li S (2011) Vimentin as a potential molecular target in cancer therapy. Cell Mol Life Sci 68:3033–3046

    Article  CAS  Google Scholar 

  22. Mendez MG, Kojima S, Goldman RD (2010) Vimentin induces changes in cell shape, motility and adhesion during the epithelial to mesenchymal transition. FASEB J 24:1838–1851

    Article  CAS  Google Scholar 

  23. Schoumacher M, Goldman RD, Louvard D, Vignjevic DM (2010) Actin, microtubules and vimentin intermediate filaments cooperate for elongation of invadopodia. J Cell Biol 189:541–556

    Article  CAS  Google Scholar 

  24. Li M, Zhang B, Sun B, Wang X, Ban X, Sun T, Liu Z, Zhao X (2010) A novel function for vimentin: the potential biomarker for predicting melanoma hematogenous metastasis. J Exp Clin Cancer Res 11:129

    Google Scholar 

  25. Shang Y, Li Z, Li H, Xia H, Lin Z (2013) TIM-3 expression in human osteosarcoma: correlation with the expression of epithelial–mesenchymal transition-specific biomarkers. Oncol Lett 6:490–494

    Article  Google Scholar 

  26. Oblak ML, Boston SE, Woods JP, Nykamp S (2013) Comparison of concurrent imaging modalities for staging of dogs with appendicular primary bone tumours. Vet Comp Oncol 13:28–39

    Article  Google Scholar 

  27. Eberle N, Fork M, Von Babo V, Nolte I, Simon D (2011) Comparison of examination of thoracic radiographs and thoracic computed tomography in dogs with appendicular osteosarcoma. Vet Comp Oncol 9:131–140

    Article  CAS  Google Scholar 

  28. Yang Y, Niu X, Liu W, Xu H (2017) Expression and significance of secreted protein acidic and rich in cysteine in human osteosarcoma. Oncol Lett 14:5491–5496

    PubMed  PubMed Central  Google Scholar 

  29. Chlenski A, Cohn SL (2010) Modulation of matrix remodeling by SPARC in neoplastic progression. Semin Cell Dev Biol 21:55–65

    Article  CAS  Google Scholar 

  30. Ribeiro N, Sousa SR, Brekken RA, Monteiro FJ (2014) Role of SPARC in bone remodeling and cancer-related bone metastasis. J Cell Biochem 115:17–26

    Article  CAS  Google Scholar 

  31. Chen H, Kolman K, Lanciloti N, Nerney M, Hays E, Robson C, Chandar N (2012) p53 and MDM2 are involved in the regulation of osteocalcin gene expression. Exp Cell Res 318:867–876

    Article  CAS  Google Scholar 

  32. Kim YS, Paik IY, Rhie YJ, Suh SH (2010) Integrative physiology: defined novel metabolic roles of osteocalcin. J Korean Med Sci 25:985–991

    Article  CAS  Google Scholar 

  33. Chen H, Hays E, Liboon J, Neely C, Kolman K, Chandar N (2011) Osteocalcin gene expression is regulated by wild-type p53. Calcif Tissue Int 89:411–418

    Article  CAS  Google Scholar 

  34. Lee JS, Tung C (2013) Osteotropic cancer diagnosis by an osteocalcin inspired molecular imaging mimetic. Biochim Biophys Acta 1830:4621–4627

    Article  CAS  Google Scholar 

  35. Won KY, Lee CH, Kim YW, Park YK (2011) Primary giant-cell-rich osteosarcoma of the urinary bladder: usefulness of osteocalcin and osteonectin immunohistochemical staining and literature review. Pathology 43:161–164

    Article  Google Scholar 

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Authors and Affiliations

  1. Departamento de Medicina Veterinária, Faculdade de Medicina Veterinária, Universidade Federal do Espírito Santo, Alegre, ES, 29500-000, Brazil

    Camila Barbosa Amaral

  2. Programa de Pós-Graduação em Clínica e Reprodução Animal, Universidade Federal Fluminense, Niterói, Brazil

    Camila Barbosa Amaral

  3. Departamento de Clínica e Patologia Veterinária, Programa de Pós-Graduação em Clínica e Reprodução Animal, Faculdade de Veterinária, Universidade Federal Fluminense, Niterói, RJ, 24230-360, Brazil

    Juliana da Silva Leite & Ana Maria Reis Ferreira

  4. Departamento de Estatística, Instituto de Matemática e Estatística, Universidade Federal Fluminense, Niterói, RJ, 24210-201, Brazil

    Ana Beatriz Monteiro Fonseca

Authors
  1. Camila Barbosa Amaral
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  2. Juliana da Silva Leite
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  3. Ana Beatriz Monteiro Fonseca
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  4. Ana Maria Reis Ferreira
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Correspondence to Camila Barbosa Amaral.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. The study was approved by the Universidade Federal Fluminense Ethics Committee in Animal Use under protocol nº 140 and all procedures were authorized by the owners after previous explanation. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Amaral, C.B., Leite, J.d., Fonseca, A.B.M. et al. Vimentin, osteocalcin and osteonectin expression in canine primary bone tumors: diagnostic and prognostic implications. Mol Biol Rep 45, 1289–1296 (2018). https://doi.org/10.1007/s11033-018-4285-6

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  • DOI: https://doi.org/10.1007/s11033-018-4285-6

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