title: Molecular and phenotypic analysis of poorly differentiated sinonasal neoplasms: an integrated approach for early diagnosis and classification.
abstract: Primary poorly differentiated (small round and non-small) sinonasal neoplasms comprise histogenetically and biologically diverse entities with overlapping morphologic features. Because of the limited initial biopsy tissue materials, differential diagnostic difficulties may arise and complicate timely management of some cases. We used immunohistochemical and molecular marker analyses in a large cohort of these tumors to optimize their early diagnosis and classification. Fifty-two tumors of the skull base and sinonasal regions and, for comparison, 19 poorly differentiated neoplasms of other head and neck sites were analyzed by a panel of immunohistochemical markers including those of epithelial, mesenchymal, melanocytic, and neuroectodermal origin using tissue microarray. Reverse transcriptase-polymerase chain reaction analysis of messenger RNA for EWS-FLI1 and PAX-FKHR fusion transcripts and the human achaete-scute homolog-1 gene was performed on 24 of the 52 sinonasal tumors and the 19 tumors of other sites for comparison. The immunohistochemical results substantiated the phenotypic assessment and the initial diagnosis in 49 of the 52 tumors. In 4 instances the integrated markers and phenotypic analyses led to reclassification of 3 tumors and confirmed the histogenesis of a mesenchymal tumor with aberrant cytokeratin expression. Molecular analysis of the EWS-FLI1 fusion gene transcript revealed 4 (9.3%) of the 43 tumors to be positive; all were Ewing sarcomas. The human achaete-scute homolog-1 gene transcript was identified in 10 (23.8%) of 42 tumors: 3 of 6 neuroblastomas, all 4 neuroendocrine carcinomas, and 1 each in sinonasal undifferentiated carcinoma, rhabdomyosarcoma, and melanoma. The PAX-FKHR fusion transcript was not detected in any tumors. We conclude that (1) an integrated morphologic and biomarker algorithm may better optimize the early diagnosis of poorly differentiated sinonasal and skull-base tumors; (2) molecular analysis may assist in future biological stratification of certain classes of these tumors; and (3) the human achaete-scute homolog-1 gene transcript is a nonspecific marker for the diagnosis of neuroblastoma.
authors.affiliation: Bobby R. Alford Department of Otolaryngology Head and Neck Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Brett
authors.initials: B
authors.lastname: Cordes
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Williams
authors.forename: Yamilet
authors.initials: Y
authors.lastname: Tirado
authors.forename: Diana
authors.initials: D
authors.lastname: Bell
authors.forename: David I
authors.initials: DI
authors.lastname: Rosenthal
authors.forename: Saleh F
authors.initials: SF
authors.lastname: Al-Dhahri
authors.forename: Ehab Y
authors.initials: EY
authors.lastname: Hanna
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D018278:Carcinoma, Neuroendocrine / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis; D055088:Early Detection of Cancer; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D008545:Melanoma / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics; D025202:Molecular Diagnostic Techniques / Q000379:methods; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D010255:Paranasal Sinus Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics; D010256:Paranasal Sinuses / Q000737:chemistry / Q000473:pathology*; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis; D034802:RNA-Binding Protein EWS; D012208:Rhabdomyosarcoma / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics; D019292:Skull Base Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics; D046888:Tissue Array Analysis
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D012334:RNA, Neoplasm; D034802:RNA-Binding Protein EWS; C065500:ASCL1 protein, human; C106031:EWS-FLI fusion protein