Histologic and genetic advances in refining the diagnosis of "undifferentiated pleomorphic sarcoma"

Abstract

Undifferentiated pleomorphic sarcoma (UPS) is an inclusive term used for sarcomas that defy formal sub-classification. The frequency with which this diagnosis is assigned has decreased in the last twenty years. This is because when implemented, careful histologic assessment, immunohistochemistry, and ultra-structural evaluation can often determine lineage of differentiation. Further attrition in the diagnostic frequency of UPS may arise by using array-comparative genomic hybridization. Gene expression arrays are also of potential use as they permit hierarchical gene clustering. Appraisal of the literature is difficult due to a historical perspective in which specific molecular diagnostic methods were previously unavailable. The American Joint Committee on Cancer (AJCC) classification has changed with different inclusion criteria. Taxonomy challenges also exist with the older term "malignant fibrous histiocytoma" being replaced by "UPS". In 2010 an analysis of multiple sarcoma expression databases using a 170-gene predictor, re-classified most MFH and "not-otherwise-specified" (NOS) tumors as liposarcomas, leiomyosarcomas or fibrosarcomas. Interestingly, some of the classifier genes are potential molecular therapeutic targets including Insulin-like growth factor 1 (IGF-1), Peroxisome proliferator-activated receptor γ (PPARγ), Nerve growth factor β (NGF β) and Fibroblast growth factor receptor (FGFR).

Figure 1

Principle component analysis of gene expression of a series of 10 types of soft tissue tumor (synovial sarcoma, myxoid/ round cell liposarcoma, well-differentiated liposarcoma, dedifferentiated liposarcoma, lipoma, myxofibrosarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, fibrosarcoma, MFH). Gene expression overview of the 105 soft tissue tumors with 12,599 probe sets. Each square represents an individual analysed tumor; Nakayama et al. [15].