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Original Article
Diagnostic Value of MDM2 and DDIT3 Fluorescence In Situ Hybridization in Liposarcoma Classification: A Single-Institution Experience
Junhun Cho, Seung Eun Lee, Yoon-La Choi
Korean J Pathol. 2012;46(2):115-122.   Published online April 25, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.2.115
  • 7,710 View
  • 73 Download
  • 8 Crossref
AbstractAbstract PDF
Background

The amplification of murine double minutes (MDM2) is the primary feature of well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPS), while DDIT3 rearrangement is the main one of myxoid liposarcomas (MLPS). Our aim was to evaluate the added value of MDM2 amplification and DDIT3 rearrangement in making a diagnosis and classifying lipogenic tumors.

Methods

Eighty-two cases of liposarcoma and 60 lipomas diagnosed between 1995 and 2010 were analysed for MDM2 amplification and DDIT3 rearrangement using a fluorescence in situ hybridization (FISH). The subtypes of liposarcoma were reclassified according to the molecular results, whose results were reviewed with an analysis of the relevant histologic and immunohistochemical findings.

Results

One case of lipoma (1.67%) was reclassified as a WDLPS. Of the liposarcomas, 13.4% (16/82) were reclassified after the molecular testing. Five cases of MLPS were reclassified as four cases of DDLPS and one case of myxoid lipoma. Two cases of WDLPS were reclassified as one case of spindle cell lipoma and another case of myxofibrosarcoma. Four cases of DDLPS were reclassified as two cases of leiomyosarcoma, one case of angiomyolipoma and another case of fibroinflammatory lesion. Of the six cases of pleomorphic liposarcoma, five were reclassified as DDLPS.

Conclusions

In our series, a critical revision of diagnosis was found at a rate of 3.5% (5/142) after a review of the lipomatous lesions. The uses of molecular testing by MDM2 and DDIT3 FISH were valuable to make an accurate subtyping of liposarcomas as well as to differentiate WDLPS from benign lipomatous tumor.

Citations

Citations to this article as recorded by  
  • Myxoid liposarcoma with nuclear pleomorphism: a clinicopathological and molecular study
    Naoki Kojima, Takashi Kubo, Taisuke Mori, Kaishi Satomi, Yuko Matsushita, Shintaro Iwata, Yasushi Yatabe, Koichi Ichimura, Akira Kawai, Hitoshi Ichikawa, Akihiko Yoshida
    Virchows Archiv.2024; 484(1): 71.     CrossRef
  • FISH Diagnostic Assessment of MDM2 Amplification in Liposarcoma: Potential Pitfalls and Troubleshooting Recommendations
    Alessandro Gambella, Luca Bertero, Milena Rondón-Lagos, Ludovica Verdun Di Cantogno, Nelson Rangel, Chiara Pitino, Alessia Andrea Ricci, Luca Mangherini, Isabella Castellano, Paola Cassoni
    International Journal of Molecular Sciences.2023; 24(2): 1342.     CrossRef
  • Expression of CTAG1B clone EPR13780 versus DDIT3 gene rearrangement distinguishes myxoid liposarcoma from its mimics with detection of novel DDIT3 gene copy number variations
    Marwa M. Abdelaziz, Hanan Y. Tayel, Amany Abdel-Bary, Omnia M. Badawy
    Journal of Histotechnology.2022; 45(2): 56.     CrossRef
  • Musculoskeletal Tumors
    Amit Singla, David S. Geller
    Pediatric Clinics of North America.2020; 67(1): 227.     CrossRef
  • Vulvar Myxoid Liposarcoma, an Extremely Rare Diagnosis: A Case Report and Review of Literature
    Ligia Redroban, Nelson Montalvo
    International Journal of Gynecological Pathology.2019; 38(1): 17.     CrossRef
  • Molecular updates in adipocytic neoplasms✰
    Elizabeth G. Demicco
    Seminars in Diagnostic Pathology.2019; 36(2): 85.     CrossRef
  • Application of MDM2 Fluorescence In Situ Hybridization and Immunohistochemistry in Distinguishing Dedifferentiated Liposarcoma From Other High-grade Sarcomas
    Min Jeong Song, Kyung-Ja Cho, Jong-Seok Lee, Joon Seon Song
    Applied Immunohistochemistry & Molecular Morphology.2017; 25(10): 712.     CrossRef
  • FluorescenceIn SituHybridization forMDM2Amplification as a Routine Ancillary Diagnostic Tool for Suspected Well-Differentiated and Dedifferentiated Liposarcomas: Experience at a Tertiary Center
    Khin Thway, Jayson Wang, John Swansbury, Toon Min, Cyril Fisher
    Sarcoma.2015; 2015: 1.     CrossRef
Case Report
Leiomyosarcoma of the Esophagus: Report of two cases, one with associated squamous cell carcinoma.
Sug Kyoung Ko, Man Ha Huh
Korean J Pathol. 1995;29(6):783-791.
  • 1,498 View
  • 12 Download
AbstractAbstract PDF
Two new cases of leiomyosarcoma of the esophagus, one with an associated squamous cell carcinoma, are presented with review of literature. lmmunohistochemical study of MDM2 gene is performed upon these cases, and one case revealed overexpression of the MDM2 protein, whereas the other case showed negative result. And the pathological significance of MDM2 gene expression in esophageal leimyosarcoma is discussed, as, to our knowlege, no esophageal leiomyosarcoma with confirmed MDM2 gene amplification has been reported in the literature, to date. Gross character of these tumors was polypoid. Microscopically, the tumors consisted of interlacing fascicles of elongated spindle-shaped cells. Mitoses could be found without difficulty, with more than five per 10 high power fields. The tumor cells of the both cases showed imunohistochemical reactivity for vimentin and actin. Electron microscopically parallel arrays of myofilaments with interspersed dense bodies in spindle cell components were confirmed. The itera-literature regarding the association of leiomyosarcoma with epithelial malignancy in the gastrointestinal tract as well as esophagus is reviewed, and we found that this is a highly unusual occurrences(3 cases reported so far).
Original Article
Expression of p53 and MDM2 Proteins in Thyroid Carcinomas.
Chang Hun Lee
Korean J Pathol. 1998;32(4):255-260.
  • 1,375 View
  • 14 Download
AbstractAbstract PDF
The nuclear protein p53 is a tumor suppressor gene product that functions in pathways of cell cycle control and in the repair of damaged DNA. The MDM2 gene codes for a cellular protein that can complex the p53 gene product and negatively regulate its function. Interestingly an autoregulatory feedback loop is set up to regulate the activity of p53 protein and MDM2 gene expression. To evaluate the role of p53 and MDM2 proteins in thyroid carcinogenesis, the author tried immunohistochemical studies in the paraffin embedded sections of 58 thyroid carcinoma cases, including 30 papillary carcinomas, 20 follicular carcinomas, and 8 undifferentiated carcinomas. p53 protein expression was found in 8 cases (26.7%) of papillary carcinomas. It was found in all the cases of undifferentiated carcinomas and not found in the follicular carcinomas. The staining intensity and the frequency scores were more prominent in undifferentiated carcinomas. MDM2 protein expression was found in only 6 cases of papillary carcinomas. It was not expressed in follicular carcinomas or undifferentiated carcinomas. The staining intensity is less than moderate and the frequency score was usually focal. In papillary carcinomas, the correlation of p53 and MDM2 expression was insignificant. In conclusion, p53 may play a major role in tumorigenesis or the progression of undifferentiated carcinomas, but not in the other carcinomas. As compared with papillary carcinomas, follicular carcinomas are regarded as taking a different carcinogenetic pathway. The overexpression of p53 and MDM2 proteins in papillary carcinomas is presumed not to be necessarily correlated with the p53-MDM2 complex formation.

J Pathol Transl Med : Journal of Pathology and Translational Medicine