Proliferative Activity of Canine Mast Cell Tumours Evaluated by Bromodeoxyuridine Incorporation and Ki-67 Expression

Sakai, Hiroki; Noda, Ayako; Shirai, Norimitsu; Iidaka, Takeshi; Yanai, Tokuma; Masegi, Toshiaki

doi:10.1053/jcpa.2002.0586

Cited by 47 publications

(56 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%

“…39,59,61 In previous studies, PCNA and Ki67 immunostaining and AgNOR histochemical staining have been shown to be independent prognostic markers for canine MCTs. 1,3,52,53,56 Although these studies have demonstrated the prognostic significance of these proliferation markers, the methods and results of these studies are varied, thereby confounding the interpretation and application of each individual study.…”

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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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“…GFAP-positive reactive astrocytes and neurofilament-positive neurites were also found in the lesion, while the anaplastic pleomorphic histiocytic cells were completely negative for these antibodies. As described previously [12], Ki-67 labeling index was investigated, and the number of Ki-67-positive neoplastic cells including multinucleated giant cells was approximately 41% of the nuclei, indicating high proliferating activity. The immunohistochemical and morphological natures of the neoplastic cells indicated that the cells were monocytic/histiocytic origin.…”

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Histiocytic Sarcoma in the Brain of a Cat

Uchida

Tamura³

et al. 2010

J. Vet. Med. Sci.

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ABSTRACT. A mass lesion in the subependymal region of the lateral ventricle in a 13-year-old neutered male mongrel cat with a complaint of somnolence, right circling movement and posture abnormality was examined. The magnetic resonance image examination revealed a relatively large T1-hypointense and T2-hyperintense mass lesion in the left interventricular foramen region, and there were no abnormalities in the chest and abdominal x-ray radiographic, funduscopic, and electric retinogram findings. The cat was died 43 days after the initial referral, and the post-mortem examinations revealed a poorly demarcated subependymal mass. Histologically, the brain lesion consisted of complex proliferation of highly pleomorphic cells resembling histiocytes with atypia and abundant mitotic figures. Moderate infiltrates of small reactive lymphocytes were admixed with the pleomorphic cell population. Gemistcytic astrocytes were also intermingled with the periphery of neoplastic foci. Immunohistochemically, most of the pleomorphic cells were positive for HLA-DR alphachain and ionized calcium binding adaptor molecule 1, and few were positive for lysozyme and alpha-1 antichymotrypsin. The atypical pleomorphic cells were negative for CD3, IgG (H and L), glial fibrillary acidic protein and neurofilament, suggesting monocytic/histiocytic-origin of the cells. The number of Ki-67-positive cell nuclei was extremely large, reflecting the high growth activity of these cells. Based on the findings, the lesion was considered as histiocytic sarcoma.KEY WORDS: brain, feline, histiocytic sarcoma, immunohistochemistry.J. Vet. Med. Sci. 72(1): 99-102, 2010 In dogs, histiocytic disorders have been classified into 3 major categories: canine cutaneous histiocytoma; canine reactive histiocytoses (both cutaneous and systemic); and histiocytic sarcoma complex (both localized and disseminated histiocytic sarcoma) [10]. Cats, in contrast, are rarely affected by these diseases [6]. Histiocytic sarcoma (HS) in cats has been reported to date in the intestinal wall, femur, tarsus, spleen and liver, and mediastinal and vertebral canals [1,5,11,13,16]. A brief description of an HS in the central nervous system (CNS) of a cat was reported only in a review article [19], while malignant histiocytic disorders have been well demonstrated in the canine CNS [2,4,14,18,20]. This report documents the features of a brain tumor in a cat. The histological and immunohistochemical natures characterized by the proliferation of highly pleomorphic cells resembling histiocytes and immunoreactivity for HLA-DR and ionized calcium binding adaptor molecule 1 (Iba1) are consistent with HS [7,8,15].A 13-year-old neutered male mongrel cat was presented to a private animal hospital with a complaint of somnolence, blindness, right circling movement and posture abnormality. The neurological examinations revealed a postural reaction decrease, a left mydriasis and disappearance of a physiologic nystagmus. Complete blood cell count and serum biochemical analyses were within normal ranges...

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“…The clinical course of each dog with CCMT varied from benign to highly malignant. Various prognostic factors have been studied, including clinical stage, surgical resection [13,21,27], kinetic parameters (Ki-67 [1,19], BrDU [19], PCNA [23], AgNOR [11]), DNA ploidy [2], intratumoral vessel density [18], p53 [7,8], KIT [9,25,26], nuclear morphometry [24], tumor depth [10] and location [4].…”

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Prognostic Significance of Surgical Margin, Ki-67 and Cyclin D1 Protein Expression in Grade II Canine Cutaneous Mast Cell Tumor

et al. 2007

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ABSTRACT. The prognosis for canine cutaneous mast cell tumor (CCMT) is thought to be correlated with histopathological grading. However, the wide variety of histopathologic types of grade II is one of the most troublesome and difficult points for prognosis. The objective of this study is to determine the prognostic value of surgical margin, ki-67 and cyclin D1 protein expression in grade II tumor. Surgically resected specimens of solitary grade II CCMT from 48 dogs with follow-up periods over 360 days (median was 1080 days) were used in this study. The expression of cyclin D1 and ki-67 proteins was determined by morphometrically using slides stained immunocytochemically, and the correlations among the results, survival rate, and recurrence and/or metastasis rate of each dog were analyzed statistically. The recurrence and/or metastasis and mortality rate in the incomplete surgical excision group within 30 months postoperatively were higher than that of the complete surgical excision group. In the incomplete surgical excision group, dogs with low positive staining of ki-67 had a significantly better survival, but the recurrence and metastasis rate and ki-67 positivity failed to show a significant correlation. Only a small number of cases showed cyclin D1-positive tumor cells, but most of them had a poor outcome with a high recurrence rate. In grade II CCMT, incomplete excision induced a relatively high metastasis rate and poor prognosis. Ki-67 positivity is a marker for the estimation of overall survival in incomplete surgical excision cases. Cyclin D1 positivity was low and may not have a prognostic role. KEY WORDS: canine, cyclin D1, ki-67, mast cell tumor, skin.J. Vet. Med. Sci. 69(11): 1117-1121, 2007 Cutaneous mast cell tumors (CCMT) are the most common round cell neoplasm in dogs, accounting for 7 to 21% of all skin tumors [12,16] The most accurate and commonly used prognostic factor is histological grade. Among the histological grading systems, Patnaik's method has been the most commonly used around the world [3,17], and the prognostic significance of this method was confirmed in other studies [1,7,8,23]. According to Patnaik's system, CCMT is classified into 3 categories on the basis of morphologic grading: grade I tumors are the most differentiated and have a good prognosis, grade III tumors are poorly differentiated with a poor prognosis, and grade II shows an intermediate differentiation with good to poor prognosis. Using this grading system, the prognosis of grade I and III tumors can be readily determined well [17]. However, other parameters have been needed for precise prognosis of grade II tumors, which have shown an inconsistent prognosis, the marked degree of inter-observer variation and accounted for 40% or 59% of CCMT [15,17].The relationships among surgical margin and prognosis or recurrence have been reported by several researchers. In grade II tumors, a complete surgical margin accurately predicted a good prognosis [21,27]. The frequency of recurrence in the complete surgical excision cases w...

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Proliferative Activity of Canine Mast Cell Tumours Evaluated by Bromodeoxyuridine Incorporation and Ki-67 Expression

Cited by 47 publications

References 34 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

Histiocytic Sarcoma in the Brain of a Cat

Prognostic Significance of Surgical Margin, Ki-67 and Cyclin D1 Protein Expression in Grade II Canine Cutaneous Mast Cell Tumor

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