title: Correlation between histology and PAX/FKHR fusion status in alveolar rhabdomyosarcoma: a report from the Children's Oncology Group.
abstract: At the molecular level, alveolar rhabdomyosarcomas (ARMS) are characterized by 3 mutually exclusive PAX/FKHR conditions: PAX3/FKHR fusion (present in 60% of cases), PAX7/FKHR fusion (present in 20%), and PAX/FKHR fusion-negativity (present in 20%). The possibility of morphologic variation among these molecular subtypes has not been investigated. We undertook a blinded retrospective study of 65 cases of ARMS (16 PAX/FKHR fusion-negative, 36 PAX3/FKHR-positive, and 13 PAX7/FKHR-positive by routine reverse transcription-polymerase chain reaction). We evaluated cytohistologic parameters such as microcyst formation, solid foci, differentiation, giant cell formation, anaplasia, nuclear grade, mitosis/karyorrhexis index, rosette formation, geographic necrosis, presence and amount of rhabdomyoblastic differentiation, and the presence of foci resembling embryonal rhabdomyosarcoma. We analyzed the results using a simple chi formula. Of these features, only totally solid alveolar architecture reached significance (P=0.00014), with 7 of 16 PAX/FKHR-negative cases lacking this feature, compared with 0 of 36 PAX3/FKHR cases and 2/13 PAX7/FKHR cases. These preliminary results indicate that in general, only totally solid alveolar architecture in ARMS may predict the absence of a PAX/FKHR fusion. No features seemed to predict the presence of a particular fusion type. Our results suggest that histologic assessment of ARMS has limited correlation with PAX/FKHR fusion status.
authors.affiliation: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA. parhamdavidm@uams.edu
authors.forename: David M
authors.initials: DM
authors.lastname: Parham
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Qualman
authors.forename: Lisa
authors.initials: L
authors.lastname: Teot
authors.forename: Frederic G
authors.initials: FG
authors.lastname: Barr
authors.forename: Raphaella
authors.initials: R
authors.lastname: Morotti
authors.forename: Poul H B
authors.initials: PH
authors.lastname: Sorensen
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Triche
authors.forename: William H
authors.initials: WH
authors.lastname: Meyer
mesh_terms: D002648:Child; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D000072041:PAX3 Transcription Factor; D051763:PAX7 Transcription Factor / Q000235:genetics; D051761:Paired Box Transcription Factors / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics* / Q000473:pathology*
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D015514:Oncogene Proteins, Fusion; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human; D051761:Paired Box Transcription Factors