Loss of Heterozygosity and Microsatellite Instability Are Rare in Sporadic Dedifferentiated Liposarcoma: A Study of 43 Well-Characterized Cases

Abstract

Context.-Defects in mismatch repair proteins have been identified in Lynch syndrome-associated liposarcomas, as well as in rare sporadic sarcomas. However, it is unclear if mismatch repair defects have a role in sarcoma tumorigenesis. Microsatellite instability is a surrogate marker of mismatch repair defects.Objectives.-To determine whether sporadic dedifferentiated liposarcomas display microsatellite instability and, if so, to evaluate whether such instability differs between the lipogenic and nonlipogenic components of these tumors.Design.-The diagnoses of conventional dedifferentiated liposarcoma were confirmed by a combination of morphologic, immunophenotypic, and molecular studies. Standard fluorescence-based polymerase chain reaction, including 5 mononucleotide microsatellite markers (BAT25, BAT26, NR21, NR24, and MONO27), as well as 2 pentanucleotide repeat markers (Penta C and Penta D), was used to test for instability and loss of heterozygosity.Results.-We demonstrated only a single case (1 of 43) with microsatellite instability at one mononucleotide marker. No sarcomas showed high-level microsatellite instability. However, loss of heterozygosity at the pentanucleotide markers was observed in 8 of 43 cases. The presence of loss of heterozygosity was overrepresented in the nonlipogenic (dedifferentiated) components compared with the paired lipogenic (well differentiated) components.Conclusions.-Mismatch repair defects do not contribute to sporadic dedifferentiated liposarcoma tumorigenesis. Whether the observed loss of heterozygosity drives tumorigenesis in liposarcoma, for example by affecting tumor suppressor or cell cycle regulator genes, remains to be determined.

The Heart of the Matter: A Unique Convergence of Cardiac Neoplasm, Hereditary Nonpolyposis Colorectal Cancer, and Spindle Cell Sarcoma

“…67 While a few sarcomas, including leiomyosarcoma and undifferentiated pleomorphic sarcoma, have been associated with Lynch syndrome, liposarcoma is the most frequent. [67][68][69][70][71][72] A prospective study of 658 adults with soft tissue sarcoma revealed that 2.8% of those patients had a genetic syndrome, predominantly Recklinghausen neurofibromatosis and bilateral retinoblastoma. 73 While reports of rhabdomyosarcoma 67 and gastric sarcoma 74 have been identified in patients with Lynch syndrome, no reported cases of cardiac sarcoma or spindle cell sarcoma have been previously reported in patients with either constitutional mismatch-repair deficiency or Lynch syndrome.…”