Rhabdomyosarcoma : Value of myogenin expression analysis and molecular testing in diagnosing the alveolar subtype an analysis of 109 paraffin-embedded specimens

Identification of the alveolar subtype of rhabdomyosarcoma (ARMS) is important, because the poor prognosis associated with this subtype necessitates a modified therapeutic regimen. At present, ARMS diagnoses are made on the basis of histologic findings and the extent of myogenin immunopositivity. No...

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Bibliographic Details
Published in:Cancer 2004-12, Vol.101 (12), p.2817-2824
Main Authors: HOSTEIN, Isabelle, ANDRAUD-FREGEVILLE, Marie, COINDRE, Jean-Michel, GUILLOU, Louis, TERRIER-LACOMBE, Marie-Jose, DEMINIERE, Colette, RANCHERE, Dominique, LUSSAN, Catherine, LONGAVENNE, Elisabeth, NGUYEN BINH BUI, DELATTRE, Olivier
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Biological and medical sciences
Child
Child, Preschool
Diseases of the osteoarticular system
DNA-Binding Proteins
Forkhead Box Protein O1
Forkhead Transcription Factors
Frozen Sections
Humans
Infant
Infant, Newborn
Medical sciences
Middle Aged
Myogenin - metabolism
Oncogene Proteins, Fusion - metabolism
Paired Box Transcription Factors
Paraffin Embedding
PAX3 Transcription Factor
Reverse Transcriptase Polymerase Chain Reaction
Rhabdomyosarcoma, Alveolar - diagnosis
Rhabdomyosarcoma, Alveolar - genetics
Rhabdomyosarcoma, Alveolar - metabolism
Rhabdomyosarcoma, Embryonal - diagnosis
Transcription Factors
Tumors
Tumors of striated muscle and skeleton
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Summary:Identification of the alveolar subtype of rhabdomyosarcoma (ARMS) is important, because the poor prognosis associated with this subtype necessitates a modified therapeutic regimen. At present, ARMS diagnoses are made on the basis of histologic findings and the extent of myogenin immunopositivity. Nonetheless, the absence of an alveolar pattern in the solid variant, the low degree of differentiation in certain embryonal rhabdomyosarcomas (ERMS), and the increasing use of microbiopsy samples make the diagnosis of ARMS somewhat difficult. Two specific translocations have been found in ARMS, and fusion transcripts can be detected by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of paraffin-embedded tissue (PET). To assess the value of myogenin staining and molecular testing in the diagnosis of rhabdomyosarcoma, the authors examined 109 rhabdomyosarcoma samples (45 ARMS samples and 64 ERMS samples). Real-time RT-PCR analysis of PET was performed in all 109 rhabdomyosarcomas, and RT-PCR analysis of frozen material was performed in 24 cases. PAX fusion transcripts were present in 44 cases (39 ARMS and 5 ERMS) and absent in 52 cases (2 ARMS and 50 ERMS). In 13 cases (4 ARMS and 9 ERMS), the results were not interpretable. Results were concordant between paired frozen and fixed tumor samples. All 35 interpretable ERMS samples that contained < 50% myogenin-positive cells failed to yield detectable PAX fusion transcripts. Of the 61 interpretable tumor samples (41 ARMS and 20 ERMS) that contained > 50% myogenin-positive cells, 44 (39 ARMS and 5 ERMS) yielded detectable PAX fusion transcripts. The current study demonstrates that molecular detection of PAX fusion transcripts via real-time RT-PCR analysis of PET is a sensitive and specific method for the diagnosis of ARMS and that immunohistochemical analysis of myogenin expression can be used to select cases for such molecular testing. Although RT-PCR analysis appears not to possess diagnostic value in tumors with < 50% tumor cell immunopositivity, it is strongly recommended for the diagnosis of tumors containing > 50% myogenin-positive cells.
ISSN:0008-543X
1097-0142
DOI:10.1002/cncr.20711