Lack of SYT-SSX Fusion Transcripts in Malignant Peripheral Nerve Sheath Tumors on RT-PCR Analysis of 34 Archival Cases

Abstract

SUMMARY:The translocation t(X;18) is currently regarded as a specific molecular marker of synovial sarcoma (SS). Recently, however, it has been reported that malignant peripheral nerve sheath tumors expressed this marker in 75% of the cases. To test independently this iconoclastic claim, a molecular analysis for the detection of the SYT-SSX fusion genes was carried out using archival material of 34 consecutive cases diagnosed as malignant peripheral nerve sheath tumors and treated in our Institute from 1998 to 2000. In four of these cases, the molecular analysis on fixed tissues was supplemented with an analysis on fresh frozen tissue. RNA extracted from formalin-fixed paraffin-embedded tissue blocks was evaluated for the presence of SYT-SSX1 and SYT-SSX2 fusion transcripts by RT-PCR. This analysis was extended to a wide variety of normal tissues simultaneously extracted and equally processed. Only two of the cases studied harbored SYT-SSX1 and SYT-SSX2 fusion transcripts, respectively. The diagnostic reevaluation of these two cases in light of the molecular data disclosed that one had the features of a monophasic SS and the other was compatible with that entity. Both of these tumors were strongly immunoreactive for bcl-2, confirming the diagnostic utility of this marker in this instance. Our results reaffirm the specificity of SYT-SSX for SS and suggest that an opposite claim made in a recent study may have been due to a faulty interpretation of the molecular results caused by a contamination of the samples. (Lab Invest 2002, 82:609 -618).

Detection of SS18-SSX fusion transcripts in formalin-fixed paraffin-embedded neoplasms: analysis of conventional RT-PCR, qRT-PCR and dual color FISH as diagnostic tools for synovial sarcoma

“…The majority of published evidence, including ours, argues that detection of a SS18 gene rearrangement is specific for the diagnosis of synovial sarcoma, 48,68 although there is some debate over the interpretation of finding a SS18 fusion gene in tumors with morphological features of malignant peripheral nerve sheath tumors. [69][70][71] In contrast, proving 100% sensitivity is more difficult. Indeed, several groups, including ours, demonstrate it is possible to attain at least 96% sensitivity for the detection of a SS18 gene rearrangement but none claim 100%.…”

HMGA proteins in malignant peripheral nerve sheath tumor and synovial sarcoma: preferential expression of HMGA2 in malignant peripheral nerve sheath tumor

“…21,22 Although there were occasional unconventional findings, 23 recent larger series have confirmed the specificity of STY-SSX fusion gene for the diagnosis of synovial sarcoma. 7,8,13,14,[24][25][26] In this report, we have used real-time RT-PCR to support and confirm the pathologic diagnosis of our cases and therefore the conclusions of our immunohistochemical study. In fact, the use of this approach has resulted in the reclassification of one MPNST as synovial sarcoma.…”

“…6 Since the elucidation of the specific chromosomal translocation and its associated fusion gene expression involved with synovial sarcoma, it has become clear that the gold standard for a definite diagnosis of synovial sarcoma requires a demonstration of the characteristic cytogenetic and/or molecular alteration, that is, chromosomal translocation t(X;18) and/ or its associated SYT-SSX fusion transcript. 7,8 The high mobility group proteins (HMGs) represent a subset of low molecular weight, nonhistone proteins, that function as transcription regulatory proteins that bind DNA and modify chromatin conformation. 9,10 The HMGI family members include HMGA1 and HMGA2.…”

Diagnostic applications of chromosomal translocations in bone and soft tissue sarcomas

“…Based on known overlapping histopathologic features between MPNST and synovial sarcoma, the simplest interpretation of this set of SYT-SSX-positive lesions diagnosed as MPNST is that that they are actually misdiagnosed synovial sarcomas. In fact, in several published reports, the authors used their enlightened hindsight to reassess these cases and reclassify some of them as synovial sarcomas [5]. However, in a few instances, there may be fusion-positive cases that are not as easily reclassifiable.…”

“…Therefore, the prospect of a pair of gene fusions, SYT-SSX1 and SYT-SSX2, resulting from closely related X;18 translocations in synovial sarcoma offered a very useful marker for the differential diagnosis involving this cancer [4]. In multiple investigations of fusion status in spindle cell tumors, the overwhelming majority of evidence indicated that a very small subset of lesions diagnosed as MPNST expressed either SYT-SSX fusion (approximately 4%), whereas most synovial sarcomas were positive [5,6]. Based on known overlapping histopathologic features between MPNST and synovial sarcoma, the simplest interpretation of this set of SYT-SSX-positive lesions diagnosed as MPNST is that that they are actually misdiagnosed synovial sarcomas.…”