Cyclin D1 immunohistochemical expression and somatic mutations in canine oral melanoma
Autor: | Valentina Zappulli, Elena M. Martínez de Merlo, Clarissa Zamboni, Serena Ferraresso, Laura Cavicchioli, Selina Iussich, Chiara Dal Corso, Ginevra Brocca, Massimo Castagnaro, Silvia Ferro, Alessandro Sammarco, Paloma J. de Andres |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
CCND1
Cyclin D1 dog immunohistochemistry melanoma 040301 veterinary sciences Somatic cell Biology 0403 veterinary science 03 medical and health sciences 0302 clinical medicine Dogs medicine Missense mutation Coding region Animals Dog Diseases Gene General Veterinary Melanoma 04 agricultural and veterinary sciences medicine.disease Molecular biology Stop codon Gene Expression Regulation Neoplastic Ki-67 Antigen 030220 oncology & carcinogenesis Mutation Immunohistochemistry Mouth Neoplasms |
Popis: | Canine oral melanoma (COM) is the most frequent tumour with oral localization in dogs. Copy number gains and amplifications of CCND1, a gene coding for Cyclin D1, are the most frequent chromosomal aberrations described in human non-UV induced melanomas. Twenty-eight cases of COM were retrieved from paraffin-blocks archives. A total of 4 μm thick sections were immunostained with an antibody against human Cyclin D1 and Ki-67. Cyclin D1 and Ki-67 expressions were scored through two counting methods. DNA was extracted from 20 μm thick sections of formalin-fixed paraffin-embedded blocks. Pathological and surrounding healthy tissue was extracted independently. Cyclin D1 immunolabelling was detected in 69% (18/26) while Ki-67 was present in 88.5% (23/26) of cases. Statistical analysis revealed correlation between two counting methods for Cyclin D1 (r = 0.54; P = .004) and Ki-67 (r = 0.56; P = .003). The correlation found between Ki-67 and Cyclin D1 indexes in 16/26 cases labelled by both antibodies (r = 0.7947; P = .0002) suggests a possible use of Cyclin D1 index as prognostic marker. Polymerase chain reaction analysis on CCND1 coding sequence revealed the presence of nine somatic mutations in seven samples producing synonymous, missense and stop codons. Since none of the single-nucleotide polymorphisms was found to be recurrent, it is suggested that overexpression of Cyclin D1 may be the consequence of alterations of CCND1 upstream regions or other genetic aberrations not detectable with the methodology used in this study. Future studies are needed to verify the potential use of Cyclin D1 index as prognostic indicator and to highlight the molecular events responsible for Cyclin D1 overexpression in COMs. |
Databáze: | OpenAIRE |
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