Mesh : Proto-Oncogene Proteins c-mdm2 / genetics metabolism Dogs Animals Liposarcoma / genetics veterinary pathology metabolism Tumor Suppressor Protein p53 / genetics metabolism Dog Diseases / genetics pathology Mutation Female Male In Situ Hybridization, Fluorescence High-Throughput Nucleotide Sequencing Gene Amplification Immunohistochemistry

来  源:   DOI:10.1038/s41598-024-64963-z   PDF(Pubmed)

Abstract:
Canine liposarcoma is an uncommon tumor that shares morphological similarities with its human counterpart. In dogs, the genetic features of this tumor are unknown and, based on immunohistochemical studies, amplification of the gene MDM2 and the mutation of TP53 are suspected. In this study 51 cases of primary liposarcomas were immunohistochemically stained for MDM2 and p53 and subjected to fluorescent in situ hybridization and next-generation sequencing to detect MDM2 amplification and TP53 mutations, respectively. MDM2 and p53 were expressed in 21 and 6 cases, respectively. MDM2 amplification and TP53 mutations were identified in 10 and 15 cases, respectively. Statistical analysis revealed an association of the myxoid subtype and the mitotic count with p53 expression and TP53 mutation. No association was found between MDM2 amplification and MDM2 expression or tumor subtype. These results suggest that despite morphological similarities, canine liposarcoma differs from its human counterpart, for which MDM2 amplification is diagnostic for well differentiated and de-differentiated variants, and TP53 mutations are more common in pleomorphic liposarcoma rather than the myxoid one as occur in our cases. Furthermore, canine myxoid liposarcoma likely represents a distinct disease rather than a mere morphological variant.
摘要:
犬脂肪肉瘤是一种罕见的肿瘤,与人类相似。在狗中,这种肿瘤的遗传特征是未知的,基于免疫组织化学研究,怀疑基因MDM2的扩增和TP53的突变。本研究对51例原发性脂肪肉瘤进行MDM2和p53的免疫组织化学染色,并进行荧光原位杂交和下一代测序,以检测MDM2扩增和TP53突变,分别。MDM2和p53在21和6例中表达,分别。在10例和15例中发现了MDM2扩增和TP53突变,分别。统计分析显示粘液亚型和有丝分裂计数与p53表达和TP53突变有关。MDM2扩增与MDM2表达或肿瘤亚型之间未发现关联。这些结果表明,尽管形态相似,犬脂肪肉瘤与人类不同,MDM2扩增可诊断高分化和去分化变异,TP53突变在多形性脂肪肉瘤中更常见,而不是在我们的病例中发生的粘液样。此外,犬粘液样脂肪肉瘤可能代表一种独特的疾病,而不仅仅是形态学变异。
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