Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics

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Abstract

Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in dogs are 27 times higher than in people. Prognosis in both species is relatively poor, with 5 year OSA survival rates in people not having improved in decades. For dogs, 1 year survival rates are only around ~ 45%. Improved and novel treatment regimens are urgently required to improve survival in both humans and dogs with OSA. Utilising information from genetic studies could assist in this in both species, with the higher incidence rates in dogs contributing to the dog population being a good model of human disease. This review compares the clinical characteristics, gross morphology and histopathology, aetiology, epidemiology, and genetics of canine and human OSA. Finally, the current position of canine OSA genetic research is discussed and areas for additional work within the canine population are identified.

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Cancer statistics, 2004.

Ahmedin Jemal, Ram C Tiwari, Taylor Murray … (2004)

Each year, the American Cancer Society estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival rates based on incidence data from the National Cancer Institute and mortality data from the National Center for Health Statistics. Incidence and mortality rates are age standardized to the 2000 US standard million population. A total of 1,368,030 new cancer cases and 563,700 deaths are expected in the United States in 2004. Incidence rates stabilized among men from 1995 through 2000 but continued to increase among females by 0.4% per year from 1987 through 2000. Mortality rates have decreased by 1.5% per year since 1992 among men, but have stabilized from 1998 through 2000 among women. Cancer death rates continued to decrease from the three major cancer sites in men (lung and bronchus, colon and rectum, and prostate) and from female breast and colorectal cancers in women. In analyses by race and ethnicity, African-American men and women have 40% and 20% higher death rates from all cancers combined compared with White men and women, respectively. Cancer incidence and mortality rates are lower in other racial and ethnic groups than in Whites and African Americans for all sites combined and for the four major cancer sites. However, these groups generally have higher rates for stomach, liver, and cervical cancers than do Whites. Furthermore, minority populations are more likely to be diagnosed with advanced stage disease than are Whites. Progress in reducing the burden from cancer can be accelerated by applying existing cancer control knowledge into practice among all segments of the population.

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Update on Survival in Osteosarcoma.

Megan E Anderson (2016)

Osteosarcoma is the most common primary bone malignancy in children. Treatment has evolved to include systemic chemotherapy and local control surgery. Although survival improved initially in a drastic fashion with this approach, recent decades have seen little to no further gains in this area. Limb salvage surgery evolved with effective chemotherapy and advances in imaging, and continues to improve in the recent era. This article serves as a review of survival in high-grade osteosarcoma: prognostic factors, advances in chemotherapy and surgery, late effects of chemotherapy and surgery in survivors, and future directions.

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The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis.

Chand Khanna, Xiaolin Wan, Seuli Bose … (2004)

Metastatic cancers, once established, are the primary cause of mortality associated with cancer. Previously, we used a genomic approach to identify metastasis-associated genes in cancer. From this genomic data, we selected ezrin for further study based on its role in physically and functionally connecting the actin cytoskeleton to the cell membrane. In a mouse model of osteosarcoma, a highly metastatic pediatric cancer, we found ezrin to be necessary for metastasis. By imaging metastatic cells in the lungs of mice, we showed that ezrin expression provided an early survival advantage for cancer cells that reached the lung. AKT and MAPK phosphorylation and activity were reduced when ezrin protein was suppressed. Ezrin-mediated early metastatic survival was partially dependent on activation of MAPK, but not AKT. To define the relevance of ezrin in the biology of metastasis, beyond the founding mouse model, we examined ezrin expression in dogs that naturally developed osteosarcoma. High ezrin expression in dog tumors was associated with early development of metastases. Consistent with this data, we found a significant association between high ezrin expression and poor outcome in pediatric osteosarcoma patients.

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Author and article information

Contributors

Siobhan Simpson: Siobhan.simpson@googlemail.com

Mark David Dunning: Mark.dunning@nottingham.ac.uk

Simone de Brot: Simone.DeBrot@nottingham.ac.uk

Llorenç Grau-Roma: Llorenc.Grau@nottingham.ac.uk

Nigel Patrick Mongan: Nigel.mongan@nottingham.ac.uk

Catrin Sian Rutland:

ORCID: http://orcid.org/0000-0002-2009-4898

Catrin.rutland@nottingham.ac.uk

Journal

Journal ID (nlm-ta): Acta Vet Scand

Journal ID (iso-abbrev): Acta Vet. Scand

Title: Acta Veterinaria Scandinavica

Publisher: BioMed Central (London )

ISSN (Print): 0044-605X

ISSN (Electronic): 1751-0147

Publication date (Electronic): 24 October 2017

Publication date PMC-release: 24 October 2017

Publication date Collection: 2017

Volume: 59

Electronic Location Identifier: 71

Affiliations

[1 ]ISNI 0000 0004 1936 8868, GRID grid.4563.4, Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, , The University of Nottingham, Sutton Bonington Campus, ; Loughborough, LE12 5RD UK

[2 ]ISNI 000000041936877X, GRID grid.5386.8, Department of Pharmacology, , Weill Cornell Medicine, ; 1300 York Avenue, New York, NY 10065 USA

Author information

Catrin Sian Rutland http://orcid.org/0000-0002-2009-4898

Article

Publisher ID: 341

DOI: 10.1186/s13028-017-0341-9

PMC ID: 5655853

PubMed ID: 29065898

SO-VID: dbfaf0cf-da6e-4339-8875-1abe3f55d901

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 24 March 2017

Date accepted : 18 October 2017

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100000268, Biotechnology and Biological Sciences Research Council;

Award ID: BB/J014508/1

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ScienceOpen disciplines: Veterinary medicine

Keywords: bone cancer,canine,genetics,human,molecular diagnostics,osteosarcoma,treatment

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ScienceOpen disciplines: Veterinary medicine

Keywords: bone cancer, canine, genetics, human, molecular diagnostics, osteosarcoma, treatment

Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics

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European Journal of Microbiology and Immunology

Most cited references 111

Cancer statistics, 2004.

Update on Survival in Osteosarcoma.

The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis.

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