Prognostic and predictive markers in canine tumours: Rationale and relevance. A review

Mukaratirwa, Samson

doi:10.1080/01652176.2005.9695186

Cited by 22 publications

(24 citation statements)

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“…23,36,37 The propensity for uncontrolled cellular proliferation is a hallmark of cancer, 17 and as such, measures of cellular proliferation have been used extensively to prognosticate both human 14,18,19,41,46,47,63,64 and veterinary neoplastic diseases. 1,3,20,22,24,26,29,34,49,52,53,56 In veterinary medicine, the most commonly used methods to evaluate cellular proliferation include proliferating cell nuclear antigen (PCNA) and Ki67 immunostaining and argyrophilic nucleolar organizing region (Ag-NOR) histochemical staining. 29,34 PCNA, is the auxiliary subunit of DNA polymerase delta 5,43 and is also involved in several additional processes in the nucleus, most notably DNA repair.…”

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confidence: 99%

“…1,3,20,22,24,26,29,34,49,52,53,56 In veterinary medicine, the most commonly used methods to evaluate cellular proliferation include proliferating cell nuclear antigen (PCNA) and Ki67 immunostaining and argyrophilic nucleolar organizing region (Ag-NOR) histochemical staining. 29,34 PCNA, is the auxiliary subunit of DNA polymerase delta 5,43 and is also involved in several additional processes in the nucleus, most notably DNA repair. 30 Although PCNA has an extended half-life 6 and is involved in multiple nuclear functions, 30 maximal PCNA exVet Pathol 44:298-308 (2007) pression is commonly seen in the DNA synthesis phase (S-phase) 4,25,57 of the cell cycle (S-phase index).…”

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confidence: 99%

“…16,54 The relative number of Ki67-positive cells in a given tissues is used to determine the proliferation index or the relative number of cells actively involved in the cell cycle (growth fraction). 8,16,29,34,54 AgNORs are nucleolar substructures that are involved in ribosomal RNA transcription. 11 AgNORs can be identified in histologic sections as discrete black nucleolar foci with a silver-based staining method, due to the silver affinity of associated proteins.…”

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Cellular Proliferation in Canine Cutaneous Mast Cell Tumors: Associations with c-KIT and Its Role in Prognostication

et al. 2007

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Abstract. Canine cutaneous mast cell tumor (MCT) is a common neoplastic disease in dogs. Due to the prevalence of canine MCTs and the variable biologic behavior of this disease, accurate prognostication and a thorough understanding of MCT biology are critical for the treatment of this disease. The goals of this study were to evaluate and compare the utility of the proliferation markers Ki67, proliferating cell nuclear antigen (PCNA), and argyrophilic nucleolar organizing region (AgNOR) as independent prognostic markers for canine MCTs and to evaluate the use of these markers in combination, as each marker assesses different aspects of cellular proliferation. An additional goal of this study was to evaluate the associations between cellular proliferation and c-KIT mutations and between cellular proliferation and aberrant KIT protein localization in canine MCTs. Fifty-six MCTs treated with surgical excision alone were included in this study. Each MCT was evaluated for Ki67 expression, PCNA expression, and KIT protein localization using immunohistochemistry; for AgNOR counts using histochemical staining; and for the presence of internal tandem duplication c-KIT mutations using polymerase chain reaction amplification. In this study, increased Ki67 and AgNOR counts were both associated with significantly decreased survival. On the basis of these results, we recommend that the evaluation of cellular proliferation, including evaluations of both Ki67 expression and AgNORs, should be routinely used in the prognostication of canine MCTs. Additionally, the results of this study show that MCTs with aberrant KIT protein localization or internal tandem duplication c-KIT mutations are associated with increased cellular proliferation, further suggesting a role for c-KIT in the progression of canine MCTs.

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Cellular Proliferation in Canine Cutaneous Mast Cell Tumors: Associations with c-KIT and Its Role in Prognostication

et al. 2007

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“…It has been shown that there can be significant variation in assigned histological grades by different pathologists, therefore certain level of variability could have been present in our study; however, the use of the two‐tier Kiupel system has likely minimized this, as demonstrated by previous studies . Finally, mast cell tumors are known to show intermediate differentiation, and therefore, can be unpredictable in their behavior while classified as low grade, or carry proliferative markers that indicate more aggressive biological behavior …”

Section: Discussionmentioning

confidence: 67%

Abdominal CT evaluation of the liver and spleen for staging mast cell tumors in dogs yields nonspecific results

Hughes

Szladovits²,

Drees

2019

Vet Radiology Ultrasound

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Canine mast cell tumor staging is commonly performed using abdominal ultrasonography and fineneedle aspiration cytology of masses, lymph nodes, and hepatic and splenic parenchyma. Computed tomography is used for abdominal, thoracic, or whole body imaging in staging mast cell tumors in the authors' institution enabling evaluation of multiple body areas in one examination.The aim of this study was to compare the CT examinations acquired for staging of mast cell disease to their subsequent liver and spleen cytology findings. Medical records of dogs with primary mast cell tumors that underwent abdominal CT and concurrent liver and spleen aspirates were reviewed. The CT examinations were evaluated for attenuation, size, and margination of the liver and spleen. The relationship between CT findings and cytology results was analyzed. Forty-nine dogs matched the inclusion criteria: five of forty-nine dogs with cutaneous mast cell tumors were positive for metastasis from liver and/or spleen aspirates. Of the five dogs with cytological evidence of liver or spleen metastasis, four had normal CT liver attenuation and size, one dog had concurrent primary hepatocellular neoplasia, four dogs had abnormal splenic parenchyma (two nodular and two diffuse heterogeneity), and one dog had a normal attenuation of the spleen. In four dogs, the spleen was subjectively enlarged. Computed tomographic evaluation of the liver showed no consistent pattern associated with mast cell metastasis and did not predict cytology results.Multifocal splenic hypoattenuating lesions more commonly coincided with mast cell metastasis.Sampling of the liver and spleen remains to be considered in the absence of abnormal CT findings for full staging. K E Y W O R D Scancer, canine, cytology, hepatic, metastasis, splenic

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“…In addition, cancers that develop in dogs show the same complex interplay of genetics, age, and environmental exposures as in humans [12, 33, 40, 41], and these similarities are stronger between humans and dogs than they are between humans and mice [30, 33, 42–44]. As with humans, cancer incidence in dogs is associated with increasing age, although certain cancers do display distinct epidemiological patterns between dogs and people [45, 46].…”

Section: Introductionmentioning

confidence: 99%

Canine cancer immunotherapy studies: linking mouse and human

Park¹,

Withers²,

Modiano³

et al. 2016

j. immunotherapy cancer

100

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Despite recent major clinical breakthroughs in human cancer immunotherapy including the use of checkpoint inhibitors and engineered T cells, important challenges remain, including determining the sub-populations of patients who will respond and who will experience at times significant toxicities. Although advances in cancer immunotherapy depend on preclinical testing, the majority of in-vivo testing currently relies on genetically identical inbred mouse models which, while offering critical insights regarding efficacy and mechanism of action, also vastly underrepresent the heterogeneity and complex interplay of human immune cells and cancers. Additionally, laboratory mice uncommonly develop spontaneous tumors, are housed under specific-pathogen free conditions which markedly impacts immune development, and incompletely model key aspects of the tumor/immune microenvironment. The canine model represents a powerful tool in cancer immunotherapy research as an important link between murine models and human clinical studies. Dogs represent an attractive outbred combination of companion animals that experience spontaneous cancer development in the setting of an intact immune system. This allows for study of complex immune interactions during the course of treatment while also directly addressing long-term efficacy and toxicity of cancer immunotherapies. However, immune dissection requires access to robust and validated immune assays and reagents as well as appropriate numbers for statistical evaluation. Canine studies will need further optimization of these important mechanistic tools for this model to fulfill its promise as a model for immunotherapy. This review aims to discuss the canine model in the context of existing preclinical cancer immunotherapy models to evaluate both its advantages and limitations, as well as highlighting its growth as a powerful tool in the burgeoning field of both human and veterinary immunotherapy.

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Prognostic and predictive markers in canine tumours: Rationale and relevance. A review

Cited by 22 publications

References 100 publications

Cellular Proliferation in Canine Cutaneous Mast Cell Tumors: Associations with c-KIT and Its Role in Prognostication

Cellular Proliferation in Canine Cutaneous Mast Cell Tumors: Associations with c-KIT and Its Role in Prognostication

Abdominal CT evaluation of the liver and spleen for staging mast cell tumors in dogs yields nonspecific results

Canine cancer immunotherapy studies: linking mouse and human

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