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

Abstract

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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“…Also, the CD1 is down-regulated by c-myc factor (TAPIA et al, 2009). In dogs, CD1 is also overexpressed in mammary carcinoma, squamous cell carcinoma and basal cell carcinoma (SFACTERIA et al, 2003), but not in mast cell tumors (OZAKI et al, 2007). Another important cell cycle inhibitor is the p27 protein, which increasing levels result in blocking cell cycle at S phase.…”

Comparação da eficácia do mesilato de imatinibe com a vimblastina associada a prednisona no tratamento do mastocitoma canino: estudo clínico, histopatológico, imunohistoquímico e molecular

“…A meia vida desta proteína é curta, sendo degradado aproximadamente uma hora após a mitose, sendo assim, mesmo marcações tênues podem ser consideradas positivas. O anticorpo monoclonal MIB-1 é utilizado para detecção da proteína Ki-67 expressa em tumores de cães e humanos (SCASE et al, 2006a;OZAKI et al, 2007).…”

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“…Além disso optou-se pelo uso de um valor já descrito em literatura para melhor comparação dos resultados obtidos com os já descritos, alguns autores utilizam pontos de corte próprios, com base na mediana ou nos resultados dados por uma curva ROC (OZAKI et al, 2007;STREFEZZI et al, 2010). Não foi observado diferença significativa no valor de Ki-67 nos dois grupos de estudo.…”