Correlation of DNA Ploidy to Tumor Histologic Grade, Clinical Variables, and Survival in Dogs with Mast Cell Tumors

Ayl, Rodney; Couto, C. Guillermo; Hammer, Alan S.; Weisbrode, Steven E.; Ericson, Julie G.; Mathes, Lawrence E.

doi:10.1177/030098589202900503

Cited by 58 publications

(46 citation statements)

References 12 publications

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“…Other approaches have involved the evaluation of DNA aneuploidy, Kit mutation status, and Kit staining patterns. 2,10,33 However, these tests have failed to definitively identify those MCTs, particularly grade II tumors, likely to behave in a biologically aggressive manner.…”

Section: Discussionmentioning

confidence: 99%

Mitotic Index Is Predictive for Survival for Canine Cutaneous Mast Cell Tumors

et al. 2007

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Abstract. Mitotic index (MI) is an indirect measure of cell proliferation that has been demonstrated to be a strong predictor of outcome for several human and canine cancers. The purpose of this study was to evaluate the utility of MI as a predictor of biologic behavior and survival in dogs with cutaneous mast cell tumors (MCTs). Medical records from 148 dogs with histologically confirmed MCTs were reviewed. Information regarding tumor grade, local recurrence, metastatic disease, date of death/last follow-up, and outcome was obtained. The region of the tumor with the highest overall mitotic activity was chosen for evaluation, and the MI value was defined as the number of mitotic figures/10 high-power fields (4003, 2.7 mm 2 ). A Cox proportional hazards regression model was used to compare MI with survival data. A Mann-Whitney test was used to compare MI on the basis of the development of local recurrence and metastatic disease. The MI correlated directly with tumor grade (P , .0001). The median survival time for dogs with an MI #5 was significantly longer (70 months) than for those with an MI .5 (2 months), regardless of grade (P , .001). For grade II tumors with an MI #5, the median survival time (MST) was 70 months, compared with 5 months for those with an MI .5 (P , .001). For grade III tumors with an MI #5, the MST was not reached, compared with ,2 months for those with an MI .5 (P , .001). In conclusion, MI is a strong predictor of overall survival for dogs with cutaneous MCTs and should be included as a prognostic indicator when determining therapeutic options.

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Section: Discussionmentioning

confidence: 99%

Mitotic Index Is Predictive for Survival for Canine Cutaneous Mast Cell Tumors

et al. 2007

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“…While some discordance exists in the literature, patients with MCT of any grade involving the regional lymph node (LN) or arising from a mucous membrane (e.g. gingiva, perineum, prepuce, nailbed) may also be at higher risk for eventual death from MCT [1,10,[28][29][30]. Thus, local therapies alone may be suboptimal for tumour control in these patients.…”

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confidence: 99%

Outcome and Prognostic Factors Following Adjuvant Prednisone/Vinblastine Chemotherapy for High-Risk Canine Mast Cell Tumour: 61 Cases

2006

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ABSTRACT. The medical records of 61 dogs with MCT at high risk for metastasis that were treated with prednisone and VBL following excision +/-radiation therapy were reviewed, and median disease-free interval (DFI), median overall survival time (OS) and prognostic factors assessed. Adverse effects, mostly mild, were noted in 26% of patients, usually after the first VBL dose. 6.5% experienced severe neutropenia. The DFI was 1305 days, and the OS was not reached, with 65% alive at 3 years. 100% of dogs with "high-risk" grade II MCT were alive at 3 years. The OS for dogs with grade III MCT was 1374 days. Histologic grade, location (mucous membrane vs. skin) and use of prophylactic nodal irradiation predicted outcome. Prednisone and VBL chemotherapy is well tolerated, and results in good outcomes following surgery in dogs with MCT at high risk for metastasis. High-grade and mucocutaneous tumors had a worse outcome, and the use of prophylactic nodal irradiation appeared to improve outcome in this group of dogs. KEY WORDS: canine, mastocytoma, Prednisone, vinblastine.J. Vet. Med. Sci. 68(6): 581-587, 2006 Mast cell tumour (MCT) represents the most common malignant cutaneous tumour in the dog [29]. High-grade or undifferentiated MCT (Patnaik grade III) comprise 29 to 40% of all MCT [2,14,22]. In addition to local infiltration, they have a reported metastatic rate of 55 to 96%, and are more likely to result in tumor-related death than are low-or intermediate-grade MCT [29]. While some discordance exists in the literature, patients with MCT of any grade involving the regional lymph node (LN) or arising from a mucous membrane (e.g. gingiva, perineum, prepuce, nailbed) may also be at higher risk for eventual death from MCT [1,10,[28][29][30]. Thus, local therapies alone may be suboptimal for tumour control in these patients.Survival times after surgery alone for high-grade MCT were reported in early studies as 15% at seven months, 6% at 48 months, and a median survival time (MST) of 13 weeks [2,3,22]. More recent studies have reported a MST of approximately 9 months with resection alone in dogs with high-grade MCT [20,25].Several studies have evaluated chemotherapy for the treatment of measurable MCT, and response rates from 7% to 78% have been documented [8,10,17,18,23,28]. However, few studies have evaluated the efficacy of chemotherapy as adjuvant treatment for MCT [7,28].Vinblastine (VBL) is an antimicrotubule alkaloid used in the treatment of hemolymphatic neoplasia in dogs [12], and various human malignancies [24]. We previously reported the results of a study employing prednisone/VBL for the treatment of dogs with gross, microscopic and "high-risk" MCT. An objective response rate of 44% was reported in dogs with gross disease, and there was suggestion that dogs receiving prednisone/VBL following surgery had a favorable clinical outcome compared with historical controls receiving local therapy alone [28]. However, the clinical characteristics of these patients were variable, and a relatively small number were treat...

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“…20,28 Establishing the histologic grade is a subjective process and is less useful for predicting clinical outcome in tumors of intermediate differentiation and when other clinical information, such as breed, site, and clinical stage of disease, is not known. 1,17,18,26 Despite many efforts to define criteria of malignancy in canine cutaneous mast cell tumors, this group of tumors retains a degree of unpredictability that leads most diagnosticians to regard all canine cutaneous mast cell tumors as potentially malignant. 1,11 The lesions, natural history, and clinical signs of mast cell tumors in the dog are well documented and excellent reviews are available.…”

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confidence: 99%

“…1,17,18,26 Despite many efforts to define criteria of malignancy in canine cutaneous mast cell tumors, this group of tumors retains a degree of unpredictability that leads most diagnosticians to regard all canine cutaneous mast cell tumors as potentially malignant. 1,11 The lesions, natural history, and clinical signs of mast cell tumors in the dog are well documented and excellent reviews are available. 17,18,28 The etiology of canine mast cell tumors or molecular and genetic events contributing to tumor development are largely unknown.…”

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Immunohistochemical Detection of p53 Tumor-Suppressor Protein is a Poor Indicator of Prognosis for Canine Cutaneous Mast Cell Tumors

et al. 2000

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Eighty-three canine cutaneous mast cell tumors were graded histologically and evaluated immunohistochemically for p53 tumor-suppressor protein expression. An avidin-biotin immunohistochemical protocol incorporated a rabbit polyclonal antibody (CM-1) directed against normal and mutant p53 protein. Positive staining was observed in 44.6% (37/83) of tumors and included 50% (12/24) of grade I (well differentiated) tumors, 46.9% (23/49) of grade II (intermediate differentiation) tumors, and 20% (2/10) of grade III (poorly differentiated) tumors. A statistically significantly higher proportion (P < 0.019) of tumors from the head and neck (83.3%, 10/12), stained positive for p53 than tumors from the thorax, back, abdomen, and axilla (39.4%, 13/33), legs (35.7%, 10/28), or prepuce, scrotal, or inguinal areas (44.4%, 4/9). No statistically significant difference between p53 labeling and histologic grade, breed, or tumor size was present. Survival data were available for 53/83 (63.9%) of dogs. Positive reactivity for p53 was observed in 47% (25/53) of tumors within this group, with 57.9% (11/19) of grade I, 43.3% (13/30) of grade II, and 25% (1/4) of grade III tumors labeled. Mean survival time for the 53 dogs was 12.1 months. The median survival time for dogs with grade III tumors or tumors >5 cm was statistically significantly shorter (P < 0.0001) than for dogs with grades I and II or smaller tumors. Although p53 protein abnormalities may play a role in tumor development or behavior in some canine cutaneous mast cell tumors, immunoreactivity was not associated with lack of tumor differentiation, tumor locations previously shown to demonstrate aggressive biological behavior, breed predisposition, or survival times.

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Correlation of DNA Ploidy to Tumor Histologic Grade, Clinical Variables, and Survival in Dogs with Mast Cell Tumors

Cited by 58 publications

References 12 publications

Mitotic Index Is Predictive for Survival for Canine Cutaneous Mast Cell Tumors

Mitotic Index Is Predictive for Survival for Canine Cutaneous Mast Cell Tumors

Outcome and Prognostic Factors Following Adjuvant Prednisone/Vinblastine Chemotherapy for High-Risk Canine Mast Cell Tumour: 61 Cases

Immunohistochemical Detection of p53 Tumor-Suppressor Protein is a Poor Indicator of Prognosis for Canine Cutaneous Mast Cell Tumors

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