Prognostic Significance of Serum Alkaline Phosphatase Activity in Canine Appendicular Osteosarcoma

Garzotto, Caroline K.; Berg, John W.; Hoffmann, Walter; Rand, William

doi:10.1111/j.1939-1676.2000.tb02281.x

Cited by 101 publications

(52 citation statements)

References 25 publications

(18 reference statements)

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“…A few previous studies 7,8 have identified increased total (or serum) alkaline phosphatase activity as a negative prognostic factor. However, in the cohort of dogs in the present study, an increased total alkaline phosphatase activity was not identified as affecting survival time beyond 1 year, a finding supported in another study.…”

Section: Discussionmentioning

confidence: 94%

“…2,8,12–15 Amputation of the affected limb is generally recommended in those patients in which orthopedic and neurologic disease in other limbs does not prevent the use of this procedure. 12,15 Alternatively, a wide variety of limb-sparing surgical techniques have been described.…”

Section: Discussionmentioning

confidence: 99%

“…1–5 Some factors that have been found to negatively influence prognosis include age (dogs < 5 years old or > 10 years old at the time of diagnosis), 6 elevated serum alkaline phosphatase activity, 7,8 histologic grade, 9 and lymph node metastases. 10 The overall median survival time from the time of diagnosis for dogs undergoing amputation alone has been reported to be approximately 5 months, but the addition of chemotherapy increases the overall median survival time to approximately 1 year.…”

mentioning

confidence: 99%

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Evaluation of outcome and prognostic factors for dogs living greater than one year after diagnosis of osteosarcoma: 90 cases (1997–2008)

Culp¹,

Olea‐Popelka²,

Sefton³

et al. 2014

javma

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Objective To evaluate clinical characteristics, outcome, and prognostic variables in a cohort of dogs surviving > 1 year after an initial diagnosis of osteosarcoma. Design Retrospective case series. Animals 90 client-owned dogs. Procedures Medical records for an 11-year period from 1997 through 2008 were reviewed, and patients with appendicular osteosarcoma that lived > 1 year after initial histopathologic diagnosis were studied. Variables including signalment, weight, serum alkaline phosphatase activity, tumor location, surgery, and adjuvant therapies were recorded. Median survival times were calculated by means of a Kaplan-Meier survival function. Univariate analysis was conducted to compare the survival function for categorical variables, and the Cox proportional hazard model was used to evaluate the likelihood of death > 1 year after diagnosis on the basis of the selected risk factors. Results 90 dogs met the inclusion criteria; clinical laboratory information was not available in all cases. Median age was 8.2 years (range, 2.7 to 13.3 years), and median weight was 38 kg (83.6 lb; range, 21 to 80 kg [46.2 to 176 lb]). Serum alkaline phosphatase activity was high in 29 of 60 (48%) dogs. The most common tumor location was the distal portion of the radius (54/90 [60%]). Eighty-nine of 90 (99%) dogs underwent surgery, and 78 (87%) received chemotherapy. Overall, 49 of 90 (54%) dogs developed metastatic disease. The median survival time beyond 1 year was 243 days (range, 1 to 1,899 days). Dogs that developed a surgical-site infection after limb-sparing surgery had a significantly improved prognosis > 1 year after osteosarcoma diagnosis, compared with dogs that did not develop infections. Conclusions and Clinical Relevance Results of the present study indicated that dogs with an initial diagnosis of osteosarcoma that lived > 1 year had a median survival time beyond the initial year of approximately 8 months. As reported previously, the development of a surgical-site infection in dogs undergoing a limb-sparing surgery significantly affected prognosis and warrants further study.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Evaluation of outcome and prognostic factors for dogs living greater than one year after diagnosis of osteosarcoma: 90 cases (1997–2008)

Culp¹,

Olea‐Popelka²,

Sefton³

et al. 2014

javma

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show abstract

“…In accordance with that, no mutation has been recently identified in canine β-catenin exon 3, similarly to human OSA [19], even if a limited number of cases were examinated, and a mainly cytoplasmic, but rare nuclear localization of the protein was detected [51]. Furthermore, no differences in nuclear β-catenin immunohistochemical expression were observed in samples obtained from two populations of canine OSA patients with normal or high level of serum alkaline phosphatase concentration [52], known to have negative prognostic value in canine osteosarcoma patients [53]. These results seem to be in agreement with recent investigations in human OSA [26], where no β-catenin nuclear expression was observed in 90% of human high grade OSA biopsies examinated and inhibition of the Wnt/β-catenin pathway has been demonstrated to be important in osteoblast neoplastic transformation [26].…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical investigation of cell cycle and apoptosis regulators (Survivin, β-Catenin, P53, Caspase 3) in canine appendicular osteosarcoma

et al. 2012

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BackgroundOsteosarcoma (OSA) represents the most common canine primary bone tumour. Despite several pathways have been investigated so far, few molecules have been identified as prognostic tools or potential therapeutic targets, and there is still the need to find out molecular pathways with specific influence over OSA progression to facilitate earlier prognosis and treatment.Aims of the present study were to evaluate the immunohistochemical pattern and levels of expression of a panel of molecules (survivin, β-catenin, caspase 3 -inactive and active forms- and p53) involved in cell cycle and apoptosis regulation in canine OSA samples, known to be of interest in the study also of human OSA, and to detect specific relations among them and with histological tumour grade, disease free interval (DFI) and overall survival (OS).ResultsNuclear β-catenin immunostaining was detected in normal osteoblasts adjacent to the tumour, and in 47% of the cases. Cytoplasmic and/or membranous immunostaining were also observed. Nuclear survivin and p53 positive cells were found in all cases. Moderate/high cytoplasmic β-catenin expression (≥10% positive cells) was significantly associated with the development of metastasis (P = 0.014); moderate/high nuclear p53 expression (≥10% positive cells) was significantly associated with moderate/high histological grade (P = 0.017) and shorter OS (P = 0.049). Moderate/high nuclear survivin expression (≥15% positive cells) showed a tendency toward a longer OS (P = 0,088).ConclusionsThe present results confirmed p53 as negative prognostic marker, while suggested survivin as a potential positive prognostic indicator, rather than indicative of a poor prognosis. The detection of nuclear β-catenin immunostaining in normal osteoblasts and the absent/low expression in most of the OSAs, suggested that this pathway could not play a major role in oncogenic transformation of canine osteoblasts. Further studies are needed to confirm these hypotheses.

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“…Additionally, the Abrams cell line produced large colonies in soft agar, indicating capability of anchorage-independent growth with little contact inhibition, indicative of carcinogenesis and metastatic potential. Only the Abrams cells consistently stained positively for alkaline phosphatase, an enzyme used to differentiate OSA from other soft tissue tumors on histopathology, and one that is often used to correlate with prognosis in OSA patients 7,11,20,21. In some studies, elevated serum levels of alkaline phosphatase are correlated with approximately 50% shorter survival times despite assertive treatment 7,11,19…”

Section: Discussionmentioning

confidence: 99%

Cellular and Phenotypic Characterization of Canine Osteosarcoma Cell Lines

Legare¹,

Bush²,

Ashley³

et al. 2011

J. Cancer

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Canine and human osteosarcoma (OSA) have many similarities, with the majority of reported cases occurring in the appendicular skeleton, gender predominance noted, high rate of metastasis at the time of presentation, and a lack of known etiology for this devastating disease. Due to poor understanding of the molecular mechanisms underlying OSA, we have characterized seven different OSA canine cell lines: Abrams, D17, Grey, Hughes, Ingles, Jarques, and Marisco and compared them to U2, a human OSA cell line, for the following parameters: morphology, growth, contact inhibition, migrational tendencies, alkaline phosphatase staining, heterologous tumor growth, double-strand DNA breaks, and oxidative damage. All results demonstrated the positive characteristics of the Abrams cell line for use in future studies of OSA. Of particular interest, the robust growth of a subcutaneous tumor and rapid pulmonary metastasis of the Abrams cell line in an immunocompromised mouse shows incredible potential for the future use of Abrams as a canine OSA model. Further investigations utilizing a canine cell model of OSA, such as Abrams, will be invaluable to understanding the molecular events underlying OSA, pharmaceutical inhibition of metastasis, and eventual prevention of this devastating disease.

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Prognostic Significance of Serum Alkaline Phosphatase Activity in Canine Appendicular Osteosarcoma

Cited by 101 publications

References 25 publications

Evaluation of outcome and prognostic factors for dogs living greater than one year after diagnosis of osteosarcoma: 90 cases (1997–2008)

Evaluation of outcome and prognostic factors for dogs living greater than one year after diagnosis of osteosarcoma: 90 cases (1997–2008)

Immunohistochemical investigation of cell cycle and apoptosis regulators (Survivin, β-Catenin, P53, Caspase 3) in canine appendicular osteosarcoma

Cellular and Phenotypic Characterization of Canine Osteosarcoma Cell Lines

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