title: Overexpression of P-glycoprotein, STAT3, phospho-STAT3 and KIT in spontaneous canine cutaneous mast cell tumours before and after prednisolone treatment.
abstract: Prednisolone is a glucocorticoid (GC) commonly used in the treatment of canine mast cell tumours (MCTs); however, resistance to GCs develops in many MCTs following repeated treatment. P-glycoprotein (P-gp), signal transducer and activator of transcription 3 (STAT3) and KIT (CD117) are involved in GC resistance. The aim of this study was to evaluate the response to prednisolone treatment in canine cutaneous MCTs and to investigate the levels of P-gp, STAT3, phospho-STAT3 (pSTAT3) and KIT proteins in MCTs with or without prednisolone treatment. Immunohistochemistry was performed on tumour samples from 41 dogs with cutaneous MCTs. The overall objective response rate (including complete and partial responses) was 51.8% for dogs treated with prednisolone; poorly differentiated or higher stage MCTs had a lower response rate. The median time-span of tumours to reach maximal tumour regression was 14 d (range 3-77 d); 22 (81.5%) reached maximal regression at 21 d. The majority of MCTs overexpressed both P-gp and STAT3 before and after prednisolone treatment. Reduced expression of pSTAT3 and alterations in the KIT expression pattern were observed in MCTs post-treatment. Prednisolone treatment that caused a marked reduction in tumour volume was correlated with reduced pSTAT3 expression. A cytoplasmic KIT staining pattern was correlated with a lower tumour response rate to prednisolone treatment.
authors.affiliation: Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung 40227, Taiwan.
authors.forename: Shr-Ping
authors.initials: SP
authors.lastname: Teng
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Hsu
authors.forename: Cheng-Yang
authors.initials: CY
authors.lastname: Chiu
authors.forename: Min-Liang
authors.initials: ML
authors.lastname: Wong
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Chang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D007150:Immunohistochemistry / Q000662:veterinary; D008297:Male; D034801:Mastocytoma / Q000188:drug therapy / Q000662:veterinary*; D010766:Phosphorylation; D011239:Prednisolone / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005938:Glucocorticoids; D050796:STAT3 Transcription Factor; D011239:Prednisolone; D019009:Proto-Oncogene Proteins c-kit