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Overexpression and Mutation of p53 Exons 4-8 in Canine Intestinal Adenocarcinoma
S H Cho1, B J Seung1, S H Kim1
1Department of Veterinary Pathology, Small Animal Tumor Diagnostic Center, College of Veterinary Medicine, Konkuk University, Republic of Korea.
Abstract:
p53 is mutated and overexpressed during malignant transformation, including in human colorectal cancer. This study investigated the overexpression of p53 protein and mutations in the p53 gene in canine intestinal neoplasia (CIN). Immunohistochemical analysis of p53 was carried out in formalin-fixed and paraffin wax-embedded (FFPE) sections of intestinal tissues from 35 dogs with CIN by the standard peroxidase-anti-peroxidase method. Expression of p53 protein in malignant (adenocarcinoma, n = 20) and benign (adenoma and polyp, n = 8) CINs was compared with tissue from negative controls (samples with no proliferation, n = 7). DNA was extracted from FFPE tissue from one control and 13 cases with overexpression of p53, and exons 4-8 were sequenced. p53 expression was higher in malignant than in benign tissues (P = 0.001). Sequencing was successfully performed in nine cases and mutations were confirmed in three of these cases. One non-sense mutation, one missense mutation and one germline mutation were confirmed for the three cases. This study suggests that p53 overexpression can be a prognostic factor for CIN; however, p53 overexpression in CIN may occur through a mechanism distinct from mutations within the p53 exon 4-8 region.
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