title: MDM2/CDK4 gene amplification in large/deep-seated 'lipomas': incidence, predictors and clinical significance.
abstract: This study of 140 cases assessed the incidence of MDM2/CDK4 gene amplification in lipomatous neoplasms with histological features of a lipoma but which were of clinical concern due to large size (≥50 mm) and/or deep-seated (subfascial) location. Univariate and multivariate statistical analyses were used to identify clinical, radiological and pathological predictors of gene amplification. Differences in local recurrence rates between amplified and non-amplified cases were assessed using survival analysis. The findings indicate that the incidence of MDM2/CDK4 amplification in this setting is low at 5% (95%CI 1.4-8.6%). Variables associated with amplification on univariate analysis were tumour site (thigh, p = 0.004), size (>100 mm, p = 0.033) and presence of equivocal atypia (p = 0.001). Independent predictors on multivariate analysis were size (OR 3.9, 95%CI 1.4-11.3, p = 0.012) and presence of equivocal atypia (OR 12.5, 95%CI 1.9-80.3, p = 0.008). There was no significant difference in local recurrence rates between amplified and non-amplified cases (p = 0.461) based on a median follow-up time of 31 months. Assessment for MDM2/CDK4 amplification, therefore, should be considered in 'lipomas' which are >100 mm in size, show equivocal atypia and arise in the thigh. However, the clinical significance of gene amplification in this setting is unclear and requires confirmation in larger studies.
authors.affiliation: Department of Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Nedlands, WA, Australia; School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, WA, Australia. Electronic address: ddwong@optusnet.com.au.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Wong
authors.affiliation: Department of Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Nedlands, WA, Australia.
authors.forename: Irene C
authors.initials: IC
authors.lastname: Low
authors.affiliation: Department of Diagnostic Genomics, PathWest Laboratory Medicine, QEII Medical Centre, Nedlands, WA, Australia.
authors.forename: Joanne
authors.initials: J
authors.lastname: Peverall
authors.affiliation: Department of Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Nedlands, WA, Australia.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Robbins
authors.affiliation: Department of Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Nedlands, WA, Australia.
authors.forename: Dominic V
authors.initials: DV
authors.lastname: Spagnolo
authors.affiliation: Department of Radiology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: Nairn
authors.affiliation: Perth Orthopaedic Institute, Nedlands, WA, Australia.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Carey-Smith
authors.affiliation: Perth Orthopaedic Institute, Nedlands, WA, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Wood
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008067:Lipoma / Q000145:classification / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000473:pathology; D008080:Liposarcoma / Q000145:classification / Q000000981:diagnostic imaging / Q000453:epidemiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D055815:Young Adult
chemical_list: C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4
keywords: CDK4; MDM2; amplification; lipoma; liposarcoma