This case of PNET/EWS is unique in the sense of showing the typical fusion transcript associated with this tumor both in the morphologically typical pretherapy tumor and in the sample from the post-therapy specimen showing neuroblastoma-like features.
PNET arising in the mesentery is very rare, and we distinguished PNET from other tumors by immunohistochemical examination and by demonstration of the presence of EWS-FLI1 chimeric mRNA in the tumor.
However, the reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated EWS/FLI-1 fusion transcripts, confirming the histopathologic diagnosis of PNET.
Primitive neuroectodermal tumor (PNET) is a prototypic malignant small round cell tumor of childhood that is characterized in most cases by t(11;22) resulting in an EWS-FLI1 gene fusion.
Ewing's sarcoma (ES) and primitive neuroectodermal tumor (PNET) are members of a tumor family consistently associated with chromosomal translocation and functional fusion of the EWS gene to any of several structurally related transcription factor genes.
The chimeric gene EWS/FLI-1, the hallmark of the Ewing's sarcoma and primitive neuroectodermal tumor family, encodes a fusion protein with enhanced transcriptional activation properties and preserved recognition of canonical ETS binding sites.
The t(11;22)(q24;q12) chromosomal translocation is specifically linked to ES and primitive neuroectodermal tumors and results, in the majority of cases, in the fusion of the amino terminus of the EWS gene to the carboxyl-terminal DNA-binding domain of the FLI1 gene.
Fluorescence in situ hybridization analysis of paraffin-embedded tissue revealed that three of four tumors were positive for a chromosomal translocation involving the EWS locus at 22q12, seen in more than 90% of cases of Ewing's sarcoma/malignant primitive neuroectodermal tumor.One case was not analyzable.
The t(11;22) chromosomal translocation specifically linked to Ewing sarcoma and primitive neuroectodermal tumor results in a chimeric molecule fusing the amino-terminus-encoding region of the EWS gene to the carboxyl-terminal DNA-binding domain encoded by the FLI-1 gene.
The EWS/FLI1 fusion gene found in Ewing's sarcoma and primitive neuroectodermal tumor, is able to transform certain cell lines by acting as an aberrant transcription factor.
In conclusion, the detection of t(11;22) and EWS/FLI-1 fusion transcripts is considered to provide a novel adjunctive method for diagnosing renal PNET.
These results suggest that EWS-Fli1 may play an important role in the proliferation of the tumor cells, and the EWS-Fli1 fusion RNA could be used as a target to inhibit the growth of Ewing's sarcoma and primitive neuroectodermal tumor with the specific antisense oligonucleotide.
This article reports three renal PNET that expressed EWS/FLI-1 fusion transcripts by RT-PCR, in addition to positive staining for MIC2 protein and neuron-specific enolase (NSE).
We detected 2 types of EWS-ERG chimeric mRNA in 2 ES cell lines and 1 PNET tumor sample in addition to 4 types of EWS-FLI-1 chimeric mRNA in 11 ESs (4 cell lines and 7 tumor samples) and 4 PNETs (2 cell lines and 2 tumor samples).
Significantly, the DNA binding portion of FLI-1 is the 3' part of an oncogenic fusion transcript (termed EWS-FLI) in human Ewing's sarcoma and neuroepithelioma.
The EWS gene, which maps to band q12 of human chromosome 22, is involved in a wide variety of human solid tumors including Ewing sarcoma, related primitive neuroectodermal tumors, malignant melanoma of soft parts and desmoplastic small round cell tumors.
The 11;22 chromosomal translocation specifically linked to Ewing sarcoma and primitive neuroectodermal tumor results in a chimeric molecule fusing the amino-terminal-encoding portion of the EWS gene to the carboxyl-terminal DNA-binding domain encoded by the FLI1 gene.
EWS/FLI-1 is a chimeric protein formed by a tumor-specific 11;22 translocation found in both Ewing's sarcoma and primitive neuroectodermal tumor of childhood.