Osteocalcin and Osteonectin Expression in Canine Osteosarcoma

Wehrle-Martinez, Alvaro; Dittmer, Keren E.; Aberdein, Danielle; Thompson, K. G.

doi:10.1177/0300985815626574

Cited by 24 publications

(33 citation statements)

References 23 publications

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“…Osteocalcin was detected in most but not all tumor cell lines, which is in agreement with findings from immunohistochemical assays of primary tumor tissue (40,42), and studies of human OSA (31). Osteocalcin was inconsistently detected in primary OSA tissues (40), and may be more consistent in clonal cell lines. Osteocalcin was inconsistently detected in primary OSA tissues (40), and may be more consistent in clonal cell lines.…”

Section: Discussionsupporting

confidence: 87%

Flow Cytometric Detection of Circulating Osteosarcoma Cells in Dogs

et al. 2019

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Osteosarcoma (OSA) is a malignant tumor of middle-aged dogs and adolescent humans. The clinical outcome of OSA has not improved over more than three decades, and dogs typically succumb to metastatic disease within 6 months despite tumor resection through limb amputation and adjuvant chemotherapy. Therefore, undetectable tumor cells with potential to form metastases are present at diagnosis. An assay to identify canine immortalized and primary OSA cells through flow cytometric detection of intracellular collagen 1 (Col I) and osteocalcin was optimized, and applied to blood samples from tumorbearing dogs for detection of circulating tumor cells (CTCs). Spiking variable number of OSA cells into normal dog blood recovered 50-60% of Col I positive cells with high forward and variable side light scatter. An algorithm to exclude nonviable, doublet, and autofluorescent cells was applied to sequential blood samples from three dogs obtained prior to and after limb amputation, and at approximately, triweekly intervals over 121, 142, and 183 days of chemotherapy, respectively. Dogs had >100 CTC/10 6 leukocytes prior to amputation, variably frequent CTC during chemotherapy, and an increase up to 4,000 CTC/10 6 leukocytes within 4 weeks before overt metastases or death. Sorted CTCs were morphologically similar to direct tumor aspirates and positive for Col I. Although preliminary, findings suggest that CTCs are frequent in canine OSA, more numerous than carcinoma CTC in humans, and that an increase in CTC frequency may herald clinical deterioration. This assay may enable enumeration and isolation of OSA CTC for prognostic and functional studies, respectively. OSTEOSARCOMA (OSA) is a primary bone cancer that is common in middle-aged to older, large breed dogs, and less common in humans, where children and young adults are most often affected. Therapy consisting of limb amputation or limbsparing tumor resection followed by chemotherapy (typically platinum or doxorubicin-based) is the gold standard, but the clinical outcome of OSA in dogs and humans remains poor (1-3). Dogs with OSA of the appendicular skeleton treated with amputation and chemotherapy had median survival times (STs) of 235-540 days (4), while in humans 5-year survival has been stagnant at about 60% (5). Although the median ST is relatively homogeneous, the range of ST in dogs with OSA treated identically varies from 2 to >30 months, illustrating that there is extensive heterogeneity in tumor biology and/or host response (6-8). Metastatic disease is the usual cause of spontaneous death or euthanasia, but fewer than 10% of dogs have radiographic evidence of metastasis at the time of diagnosis (2).Computed tomography also lacks sensitivity for identifying metastases, and histologic grading schemes for canine OSA poorly predict biological behavior (9-11).

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Section: Discussionsupporting

confidence: 87%

Flow Cytometric Detection of Circulating Osteosarcoma Cells in Dogs

et al. 2019

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“…The microscopic diagnosis of osteosarcoma can be challenging, especially when a small sample has been sent for the histopathological examination or cytology is the only diagnostic method used (Wehrle-Martinez et al 2016). Nevertheless, cytology is considered an accurate method of presurgical diagnosis of canine osteosarcoma (Baker and Lumsden 2000).…”

Section: Discussionmentioning

confidence: 99%

The animal-dependent risk factors in canine osteosarcomas

Sapierzyński¹,

Czopowicz²

2017

Polish Journal of Veterinary Sciences

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Canine osteosarcoma (OSA) is a malignant neoplastic tumor, which develops from the primitive mesenchymal stem cell, that has or can acquire the capacity to produce neoplastic osteoid with possible neoplastic bone formation. Predisposition of some dog breeds to OSA indicates genetic background of oncogenesis. The aim of the study was to characterize animal-dependent risk factors for canine osteosarcoma development in Poland. The study was conducted on canine patients diagnosed cytologically or histopathologically as having OSA, and data on age, breed, sex, as well as tumor location and character were recorded. No sex predisposition to OSA was observed, mongrels were significantly underrepresented. Large and giant dogs accounted for 47% and 35% of all pedigree dogs, respectively, and both proved predisposed to OSA. A vast majority of OSA developed in the skeleton (appendicular skeleton was more commonly affected than axial skeleton), soft tissues were affected less often. Rottweiler dogs are strongly predisposed to OSA, suggesting that the genetic background is involved in the tumor development, and indicates that dogs of this breed are a promising object for further studies on OSA pathogenesis.

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“…The antiosteonectin antibody is poorly sensitive and can react with various cell types including active osteoblasts, immature osteocytes, fibroblasts, and epithelial cells (PARHAM, 2015;WEHRLE-MARTINEZ et al, 2016). Anti-osteopontin antibody also has low sensitivity, and although studies have shown expression in osteosarcomas, this antibody also presents immunoreaction in the epithelium of the gastrointestinal tract, gallbladder, pancreas, urinary, and reproductive tracts, salivary and sweat glands, as well as vascular endothelial cells, macrophages, and myoepithelial cells, and there is no immunostaining.…”

Section: Intestinal Osteosarcomamentioning

confidence: 99%

“…Anti-osteopontin antibody also has low sensitivity, and although studies have shown expression in osteosarcomas, this antibody also presents immunoreaction in the epithelium of the gastrointestinal tract, gallbladder, pancreas, urinary, and reproductive tracts, salivary and sweat glands, as well as vascular endothelial cells, macrophages, and myoepithelial cells, and there is no immunostaining. in hematopoietic neoplasms (PARHAM, 2015;WEHRLE-MARTINEZ et al, 2016). The anti-osteocalcin antibody reacts with osteocytes of adult bone and presents positive immunostaining in 66.6% of cases of low-grade, well-differentiated osteosarcomas; therefore it is more specific when compared to osteonectin and osteopontin (WEHRLE-MARTINEZ et al, 2016).…”

Section: Intestinal Osteosarcomamentioning

confidence: 99%

“…The anti-osteocalcin antibody reacts with osteocytes of adult bone and presents positive immunostaining in 66.6% of cases of low-grade, well-differentiated osteosarcomas; therefore it is more specific when compared to osteonectin and osteopontin (WEHRLE-MARTINEZ et al, 2016). In contrast, the immunostaining of osteocalcin is much lower in high-grade undifferentiated osteosarcomas, so its sensitivity is lower depending on the degree of differentiation of the neoplasia (PARHAM, 2015;WEHRLE-MARTINEZ et al, 2016).…”

Section: Intestinal Osteosarcomamentioning

confidence: 99%

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The importance of clinical, histopathological and immunohistochemical marking for differential diagnosis of non-hematopoietic gastrointestinal mesenchymal neoplasms in dogs: literature review

Leandro

Freitas

Sá

2017

Braz. J. Vet. Res. Anim. Sci.

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Gastrointestinal neoplasms in dogs represent a challenge for the veterinary clinician and surgeon as they are mostly malignant and when the owner notices the primary clinical changes the disease may already be in an advanced stage. Due to the high clinical and histopathological similarity between mesenchymal gastrointestinal neoplasms, it is often impossible to establish the definitive morphological diagnosis using light microscopy alone. In addition, there are only a few articles describing the anatomopathological and immunohistochemical characteristics, which make its complete characterization urgent and relevant in our context in order to assist the veterinary clinician, surgeon, and pathologist in establishing a precise diagnosis of these tumors. Keywords: C-KIT. Sarcoma. Stomach. Intestine. Colon. Rectum. ResumoAs neoplasias gastrointestinais em cães representam casos desafiantes ao clínico e cirurgião, pois são em sua maioria malignas e, quando as primeiras alterações clínicas são notadas pelo proprietário do animal, a doença pode estar em estágio de desenvolvimento muito avançado. Devido à elevada similaridade clínica e histopatológica entre as neoplasias gastrointestinais mesenquimais, muitas vezes não é possível estabelecer o diagnóstico morfológico definitivo apenas com a microscopia de luz. Acrescenta-se que são poucos os artigos que descrevem as características anatomopatológicas e imuno-histoquímicas das neoplasias mesenquimais gastrointestinais que acometem os cães, o que torna premente a caracterização destas em nosso contexto, com o intuito de auxiliar clínico, cirurgião e patologista veterinário a estabelecer o diagnóstico destes tumores.

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Osteocalcin and Osteonectin Expression in Canine Osteosarcoma

Cited by 24 publications

References 23 publications

Flow Cytometric Detection of Circulating Osteosarcoma Cells in Dogs

Flow Cytometric Detection of Circulating Osteosarcoma Cells in Dogs

The animal-dependent risk factors in canine osteosarcomas

The importance of clinical, histopathological and immunohistochemical marking for differential diagnosis of non-hematopoietic gastrointestinal mesenchymal neoplasms in dogs: literature review

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