Clinico-molecular study of dedifferentiation in well-differentiated liposarcoma,☆☆

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Abstract

Well-differentiated liposarcoma (WD) acquires fully malignant potential when the histological progression named dedifferentiation occurs. This progression is supposed to occur in a time-dependent manner but this is still a debated issue. Clinically, the prediction of dedifferentiation for WD is very important from the therapeutic point of view. To identify genes that are predictive of dedifferentiation and to understand the mechanism of dedifferentiation, we investigated clinical information of 50 cases and studied the gene expression profiles of 36 lipomatous tumors using cDNA microarray. The clinical study showed that the dedifferentiation did not always seem to occur in a time-dependent manner. Interestingly, from the gene expression study, unsupervised hierarchical clustering analysis of well-differentiated lesions obtained from dedifferentiated liposarcoma (DD) cases that were indistinguishable from WD pathologically showed a clearly distinct gene expression pattern from WD. Using the pattern-matching program, 1687 genes including 487 known genes were identified, which discriminated WD cases from well-differentiated lipomatous lesions obtained from DD cases. These results suggest that the dedifferentiation may arise from different types of WD that could be distinguished from gene expression profiling but could hardly be classified by the pathological studies.

Section snippets

Materials and methods

Cases and methods of clinical study. Fifty cases in the WD and DD group treated in the Cancer Institute Hospital from 1978 to 2001 were studied. All samples were obtained from surgical specimens or biopsy specimens with no treatment by chemotherapy or radiotherapy.

Among the 50 cases, 5 cases had dedifferentiated lesions in the tumors. Clinical information such as localization, surgical margin, tumor size, clinical outcome, and pathological findings were examined for this study. Specimens had

Behavior of 50 well-differentiated/dedifferentiated type liposarcomas and relationship between dedifferentiation and tumor size

Fifty cases of well-differentiated and dedifferentiated type liposarcomas were studied. Out of the 5 DD cases, 2 had tumors located in the extremities and groin, respectively. The other 3 DD cases had tumors located in the retroperitoneum and died of disease after lung metastasis and local recurrences (Table 1A). The dedifferentiation of all 5 cases was aroused as a “de novo” lesion. No DD cases were seen with recurred lesions.

On the other hand, almost all WD cases had tumors located in the

Discussion

It is an interesting result that the well-differentiated lesions obtained from the DD cases showed a quite different gene expression profile from those of the WD cases by the unsupervised hierarchical clustering analysis. Although well-differentiated lesions from DD and WD are pathologically indistinguishable, our gene expression studies showed that the expression profiles are divergent.

The histological progression named dedifferentiation occurring in WD has been proposed to occur in a

Acknowledgements

This study has been supported by a Research Grant for the RIKEN Genome Exploration Research Project from the Ministry of Education, Culture, Sports, Science and Technologies of the Japanese Government and a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japanese Government. We thank Manabe J, Kuroda K, Ae K, Tanizawa K, Tomaru Y, Hoshikawa Y, and Nagasaki K for helpful discussion.

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    Abbreviations: WD, well-differentiated liposarcoma; DD, dedifferentiated liposarcoma; MX, myxoid liposarcoma; RC, round cell liposarcoma; LP, lipoma.

    ☆☆

    Supplementary data associated with this article can be found in the online version, at doi: 10.1016/j.bbrc.2003.12.203.

    1

    Present address: Division of Functional Genomics & Systems Medicine, Research Center for Genomic Medicine, Saitama Medical School, 1397-1 Yamane, Hidaka City, Saitama 350-1241, Japan.

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