title: Histological Classification and Immunohistochemical Evaluation of MDM2 and CDK4 Expression in Canine Liposarcoma.
abstract: Canine liposarcoma is an uncommon soft tissue sarcoma usually arising in the subcutis. While liposarcoma classification in dogs is based solely on histology, in humans it depends on the detection of genetic abnormalities that can lead to specific protein overexpression. This study is an immunohistochemical evaluation of MDM2 and CDK4 expression in canine liposarcoma designed to assess the correlation of these proteins with histologic type, grade, mitotic index and Ki67 labeling index and evaluate their utility in improving tumor classification. Fifty-three liposarcomas were retrospectively collected: 24 were well differentiated liposarcomas (WDL), 16 of which expressed MDM2 and 21 CDK4; 7 were myxoid liposarcomas (ML), 1 of which expressed MDM2 and 5 expressed CDK4; 18 were pleomorphic liposarcomas (PL), all were MDM2 negative and 12 expressed CDK4. Four tumors were morphologically consistent with dedifferentiated liposarcoma (DDL) a subtype described only in humans: 3 expressed MDM2 and 4 expressed CDK4. MDM2 expression correlated with histotype (highly expressed in WDL and DDL) and grade (highly expressed in grade 1 tumors). Histotype correlated with the Ki67 labeling index (lowest in WDL and highest in DDL). A revised classification, considering MDM2 expression, allowed 8 WDL to be reclassified as PL and correlated significantly with mitotic and Ki67 labeling index (both significantly lower in WDL and progressively higher in ML and DDL). These results partially parallel data reported for human liposarcomas, suggesting that WDL and DDL are distinct neoplastic entities characterized by MDM2 expression, which may represent a useful diagnostic and potentially prognostic marker for canine liposarcoma.
authors.affiliation: Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Ozzano dell'Emilia, Italy giancarlo.avallone@unibo.it.
authors.forename: G
authors.initials: G
authors.lastname: Avallone
authors.affiliation: Department of Veterinary Sciences and Public Health (DIVET), University of Milan, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Roccabianca
authors.affiliation: Istovet, Besana Brianza, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Crippa
authors.affiliation: Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Lepri
authors.affiliation: Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Ozzano dell'Emilia, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Brunetti
authors.affiliation: Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Ozzano dell'Emilia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Bernardini
authors.affiliation: Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Ozzano dell'Emilia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Forni
authors.affiliation: Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Ozzano dell'Emilia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Olandese
authors.affiliation: Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Ozzano dell'Emilia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Sarli
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism*; D004283:Dog Diseases / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D005260:Female; D007150:Immunohistochemistry / Q000662:veterinary; D008080:Liposarcoma / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D008297:Male; D060787:Neoplasm Grading / Q000662:veterinary; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D051736:Proto-Oncogene Proteins c-mdm2; D051358:Cyclin-Dependent Kinase 4
keywords: CDK4; MDM2; dedifferentiated; dog; grade; immunohistochemistry; liposarcoma; soft tissue sarcoma