Abstract
Ordinary lipomas are cytogenetically characterized by a variety of balanced rearrangements involving chromosome segment 12q13–15, whereas well differentiated liposarcomas (WDL) show supernumerary ring and giant marker chromosomes, known to contain amplified 12q sequences. The tight correlation between the presence of ring chromosomes and both amplification and overexpression of MDM2 and CDK4 genes suggests the exploration of the possibility that immunocytochemistry (ICC) might assist in the differential diagnosis of lipoma-like well differentiated liposarcomas (LL-WDL) and large deep-seated lipomas (LDSL). For this purpose, 21 cases of the former and 19 cases of the latter tumours were analysed by ICC and, according to the availability of material, by molecular and cytogenetic approaches. All lipomas displayed a null MDM2/CDK4 phenotype, whereas all LL-WDL showed MDM2/CDK4 or CDK4 phenotypes. Southern blot analysis performed on 16 suitable cases, complemented by fluorescence in situ hybridization and classical cytogenetic analysis in 11 cases, was consistent with, and further supported the immunophenotyping data. In conclusion, MDM2/CDK4 product-based immunophenotyping appears to represent a valuable method for the categorization of arguable LDSL. © 2000 Cancer Research Campaign
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References
Berner J-M, Meza-Zepeda LA, Kools PFJ, Forus A, Schoenmakers EFPM, Van de Ven WJM, Fodstad Ø and Myklebost O (1997) HMGIC, the gene for an architectural transcription factor, is amplified and rearranged in a subset of human sarcomas. Oncogene 14: 2935–2941
Dal Cin P, Kools P, Sciot R, De Wever I, Van Damme B, Van de Ven W and Van Den Berghe H (1993) Cytogenetic and fluorescence in situ hybridization investigation of ring chromosomes characterizing a specific pathologic subgroup of adipose tissue tumors. Cancer Genet Cytogenet 68: 85–90
Dei Tos AP and Dal Cin P (1997) The role of cytogenetics in the classification of soft tissue tumours. Virchows Arch 431: 83–94
DeWeerd JH and Dockerty MB (1952) Lipomatous retroperitoneal tumors. Am J Surg 84: 397–407
Evans HL (1988) Liposarcoma and atypical lipomatous tumors: a study of 66 cases followed for a minimum of 10 years. Surg Pathol 1: 41–54
Fletcher CDM, Akerman M, Dal Cin P, de Wever I, Mandhal N, Mertens F, Mitelman F, Rosai J, Rydholm A, Sciot R, Tallini G, van den Berghe H, van de Ven W, Vanni R and Willen H (1996) Correlation between clinicopathological features and karyotype in lipomatous tumors. A report of 178 cases from the chromosomes and morphology (CHAMP) collaborative study group. Am J Pathol 148: 623–630
Forus A, Flørenes VA, Maelandsmo GM, Meltzer PS, Fodstad Ø and Myklebost O (1993) Mapping of amplification units in the q13–14 region of chromosome 12 in human sarcomas: some amplica do not include MDM2. Cell Growth Differ 4: 1065–1070
Heim S and Mitelman F (1995) Cancer cytogenetics. Chromosomal and molecular genetic aberrations of tumor cells. 2nd edn, pp. 484–489. Wiley-Liss: New York
Hunter T and Pines J (1994) Cyclins and cancer. II: cyclin D and CDK inhibitors come of age. Cell 79: 573–582
Khatib ZA, Matsushime H, Valentine M, Shapiro DN, Sherr CJ and Look AT (1993) Coamplification of the CDK4 gene with MDM2 and GLI in human sarcomas. Cancer Res 53: 5535–5541
Leach FS, Tokino T, Meltzer P, Burrell M, Oliner JD, Smith S, Hill DE, Sidransky D, Kinzler KW and Vogelstein B (1993) p53 mutation and MDM2 amplification in human soft tissue sarcomas. Cancer Res 53: 2231–2234
Lichter P, Chang Tang C, Call K, Hermanson G, Evans GA, Housman D and Ward DC (1990) High resolution mapping of human chromosome 11 by in situ hybridization with cosmid clones. Science 247: 64–67
Mandahl N, Akerman M, Aman P, Dal Cin P, De Wever I, Fletcher CDM, Mertens F, Mitelman F, Rosai J, Rydholm A, Sciot R, Tallini G, van den Berghe H, Van de Ven W, Vanni R and Willen H (1996) Duplication of chromosome segment 12q15–24 is associated with atypical lipomatous tumors: a report of the CHAMP collaborative study group. Int J Cancer 67: 632–635
Mentzel T and Fletcher CDM (1995) Lipomatous tumours of soft tissues: an update. Virchows Arch 427: 353–363
Mezzelani A, Sozzi G, Pierotti MA and Pilotti S (1996) Rapid differential diagnosis of myxoid liposarcoma by fluorescence in situ hybridization on cytological preparations. J Clin Pathol: Mol Pathol 49: M308–M309
Nilbert M, Rydholm A, Willen H, Mitelman F and Mandahl N (1994) MDM2 gene amplification correlates with ring chromosomes in soft tissue tumors. Genes Chrom Cancer 9: 261–265
Pedeutour F, Suijkerbuijk RF, Van Gaal J, Van de Klundert W, Coindre J-M, Van Haelst A, Collin F, Huffermann K and Turc-Carel C (1993) Chromosome 12 origin in rings and giant markers in well-differentiated liposarcoma. Cancer Genet Gytogenet 66: 133–134
Petit MMR, Mols R, Schoenmakers EF, Mandahl N and Van de Ven WJ (1996) LPP, the preferred fusion partner gene at HMGIC in lipomas, is a novel member of the LIM protein gene family. Genomics 36: 118–129
Pilotti S, Della Torre G, Lavarino C, Di Palma S, Sozzi G, Minoletti F, Rao S, Pasquini G, Azzarelli A, Rilke F and Pierotti MA (1997) Distinct mdm2/p53 expression patterns in liposarcoma subgroups: implications for different pathogenetic mechanisms. J Pathol 181: 14–24
Pilotti S, Della Torre G, Lavarino C, Sozzi G, Minoletti F, Vergani B, Azzarelli A, Rilke F and Pierotti MA (1998) Molecular abnormalities in liposarcoma: role of MDM2 and CDK4-containing amplicons at 12q13–22. J Pathol 185: 188–190
Rosai J, Akerman M, Dal Cin P, DeWever I, Fletcher CDM, Mandhal N, Mertens F, Mitelman F, Rydholm A, Sciot R, Tallini G, Van Den Berghe H, Van De Ven W, Vanni R and Willen H (1996) Combined morphologic and karyotypic study of 59 atypical lipomatous tumors. Evaluation of their relationship and differential diagnosis with other adipose tissue tumors (a report of the CHAMP study group). Am J Surg Pathol 20: 1182–1189
Schoenmakers EFPM, Wanschura S, Mols R, Bullerdiek J, Van den Berghe H and Van de Ven WJM (1995) Recurrent rearrangements in the high mobility group protein gene, HMGI-C, in benign mesenchymal tumors. Nat Genet 10: 436–444
Smith SH, Weiss SW, Jankowski SA, Coccia MA and Meltzer PS (1992) SAS amplification in soft tissue sarcomas. Cancer Res 52: 3746–3749
Suijkerbuijk RT, Olde Weghuis DEM, Van Den Berg M, Pedeuour F, Forus A, Myklebost O, Glier C, Turc-Carel C and Geurts van Kessel A (1994) Comparative genomic hybridization as a tool to define two distinct chromosome 12 amplification units in well-differentiated liposarcomas. Genes Chromosomes Cancer 9: 292–295
Szymanska J, Virolainen M, Tarkkanen M, Wiklund T, Asko-Seljavaara S, Tukiainen E, Elomaa I, Blomqvist C and Knuutila S (1997) Overrepresentation of 1q21–23 and 12q13–21 in lipoma-like liposarcomas but not in benign lipomas: a comparative genomic hybridization study. Cancer Genet Cytogenet 99: 14–18
Tkachenko A, Ashar HR, Meloni AM, Sandberg AA and Chada KK (1997) Misexpression of disrupted HMGI architectural factors activates pathways of tumorigenesis. Cancer Res 57: 2276–2280
Willen H, Akerman M, Dal Cin P, De Wever I, Fletcher CDM, Mandahl N, Mertens F, Mitelman F, Rosai J, Rydholm A, Sciot R, Tallini G, Van Den Berghe H and Vanni R (1998) Comparison of chromosomal patterns with clinical features in 165 lipomas: a report of the CHAMP study group. Cancer Genet Cytogenet 102: 46–49
Zauberman A, Flusberg D, Haupt Y, Barak Y and Oren M (1995) A functional p53-responsive intronic promoter is contained within the human mdm2 gene. Nucleic Acids Res 23: 2584–2592
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Pilotti, S., Torre, G., Mezzelani, A. et al. The expression of MDM2/CDK4 gene product in the differential diagnosis of well differentiated liposarcoma and large deep-seated lipoma. Br J Cancer 82, 1271–1275 (2000). https://doi.org/10.1054/bjoc.1999.1090
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DOI: https://doi.org/10.1054/bjoc.1999.1090
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