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Carboxypeptidase A3 expression in canine mast cell tumors and tissue-resident mast cells.

ABSTRACT: Mast cell tumors (MCTs) are one of the most common cutaneous malignancies in dogs. Previous studies have reported expression of mast cell-specific proteases chymase and tryptase in canine cutaneous MCTs and in connective tissue and mucosal mast cells. In humans and rodents, mast cells express an additional specific protease, carboxypeptidase A3 (CPA3). In this article, we describe CPA3 immunoreactivity in connective tissue, visceral, mucosal, and neoplastic mast cells in dogs. Positive immunolabeling for CPA3 was observed in nonneoplastic mast cells in 20/20 formalin-fixed paraffin-embedded normal tissues (skin, liver, spleen, intestine), and in 63/63 MCTs irrespective of their histological grade. CPA3 protein expression was comparable to that of c-kit in both the nonneoplastic and neoplastic mast cells. Three distinct labeling patterns (membranous, diffuse, and focal cytoplasmic) were observed for CPA3 in MCTs. The focal cytoplasmic labeling pattern was associated with high-grade MCTs staged with the Kiupel 2-tier grading criteria. We propose CPA3 as a novel immunohistochemical marker for canine mast cells in health and disease.

SUBMITTER: Hamalainen S

PROVIDER: S-EPMC8928232 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Carboxypeptidase A3 expression in canine mast cell tumors and tissue-resident mast cells.

Hämäläinen Sanna S Kareinen Lauri L Sukura Antti A Kareinen Ilona I

Veterinary pathology 20211212 2

Mast cell tumors (MCTs) are one of the most common cutaneous malignancies in dogs. Previous studies have reported expression of mast cell-specific proteases chymase and tryptase in canine cutaneous MCTs and in connective tissue and mucosal mast cells. In humans and rodents, mast cells express an additional specific protease, carboxypeptidase A3 (CPA3). In this article, we describe CPA3 immunoreactivity in connective tissue, visceral, mucosal, and neoplastic mast cells in dogs. Positive immunolab ...[more]

PMID: 34894899

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Project description:BackgroundYKL-40, a secretory glycoprotein, is involved in tumor cell proliferation, metastasis, and angiogenesis in human cancers. Its overexpression has been correlated with unfavorable prognosis in many human cancers. In veterinary medicine, elevated YKL-40 levels in the serum of canine cutaneous mast cell tumors (cMCTs) were observed in our previous study. However, the expression pattern of YKL-40 in canine cMCT tissues, along with its association with clinical and pathological features, is still unknown. This study aims to retrospectively investigate the expression level of YKL-40 in the tissues of canine cMCTs and its correlation with clinical features, pathological characteristics, and clinical outcomes. Forty formalin-fixed paraffin-embedded cMCT tissues collected from forty dogs were diagnosed as low-grade (n = 20) or high-grade s(n = 20) MCT according to the Kiupel grading system. The expression level of YKL-40 in cMCT tissues was investigated using immunohistochemical staining and immunoreactivity score (IRS).ResultsYKL-40 was expressed in all cMCTs at different levels, with significantly stronger expression in low-grade cMCTs compared to high-grade cMCTs. The expression level was also associated with tumor diameter, histological grade, mitotic counts, vessel density, and survival of cMCTs. The overall survival of cMCT dogs showed significant differences (p < 0.01) among mild (n = 15, MST 219 days), moderate (n = 19, MST not reached), and high (n = 6, MST not reached) YKL-40 expression groups. Among low-grade cMCTs, overall survival was significantly different between mild YKL-40 expression (MST 319 days) and moderate to high YKL-40 (MST not reached) expression (p < 0.01). In high-grade cMCTs, overall survival was not correlated with YKL-40 expression (p = 0.6589).ConclusionsThis study found that the YKL-40 expression level was significantly stronger in low-grade than in high-grade canine cutaneous mast cell tumors and was associated with various clinical and pathological features. Stronger YKL-40 expression level correlated with longer survival time, especially in low-grade cMCTs. Therefore, YKL-40 could serve as a prognostic marker for cMCTs.

Dataset Information

Carboxypeptidase A3 expression in canine mast cell tumors and tissue-resident mast cells.

Publications

Carboxypeptidase A3 expression in canine mast cell tumors and tissue-resident mast cells.

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