Malignant fibrous histiocytoma--pleomorphic sarcoma, NOS gene expression, histology, and clinical course. A pilot study.

OBJECTIVE

The new classification of malignant fibrous histiocytoma leaves only a small group of tumors without further line of differentiation, so-called pleomorphic sarcomas, not otherwise specified (NOS) as a pseudo-entity. This study focused on these tumors and analyzed the association of gene expression profiles to clinical outcome.

METHODS

Ten fresh samples of pleomorphic NOS sarcomas were evaluated histopathologically and by means of microarray analysis. Analysis of expression profiles was performed by clustering methods as well as by statistical analysis of primary vs recurrent tumors, irradiated vs nonirradiated tumors, tumors of patients above and below 60 years of age, male and female, and of tumors that developed metastatic or recurrent disease during the clinical course and those that did not.

RESULTS

Tumor clustering did not correlate to any histopathological or clinical finding. Detailed gene expression analysis showed a variety of genes whose upregulation (platelet-derived growth factor receptor alpha polypeptide, solute carrier family 39 member 14, solute carrier family 2 member 3, pleiotrophin, trophinin, pleckstrin and Sec7 domain containing 3, enolase 2, biglycan, SH3 and cysteine-rich domain, matrix metalloproteinases 16) and whose downregulation (tissue inhibitor of metalloproteinase 4, hairy/enhancer of split related with YRPW motif 2, protein tyrosine phosphatase receptor-type Z polypeptide 1, SH3 domain GRB2-like 2, microtubule-associated protein 7, potassium voltage-gated channel shaker-related subfamily member 1, RUN and FYVE domain containing 3, Sin3A-associated protein 18 kDa, proline-rich 4, calcium/calmodulin-dependent protein kinase ID, myeloid/lymphoid or mixed-lineage leukemia translocated to 3, insulin-like growth factor binding protein 5, nucleoside diphosphate-linked moiety X-type motif 9, NudC domain containing 3, imprinted in Prader-Willi syndrome, TAF6-like RNA polymerase II p300/CBP-associated factor 65 kDa, WD repeat and SOCS box-containing 2, adenosine diphosphate ribosylation factor 3, KRR1, proliferation-associated 2G4; CD36, complement component (3b/4b) receptor 1, solute carrier family 4 sodium bicarbonate cotransporter member 4, lipoprotein lipase (LPL), GATA binding protein 3, LPL, glutathione peroxidase 3, D: -aspartate oxidase, apolipoprotein E, sphingomyelin phosphodiesterase acid-like 3A) were associated with poor clinical outcome in terms of development of metastatic or recurrent disease.

CONCLUSIONS

The classification of these tumors may undergo further changes in the future. Gene expression profiling can provide additional information to categorize pleomorphic sarcoma (NOS) and reveal potential prognostic factors in this "entity."