title: SMARCB1 (INI-1)-deficient carcinomas of the sinonasal tract.
abstract: SMARCB1 (INI-1) is a tumor-suppressor gene located on chromosome 22q11.2. Its gene product is ubiquitously expressed in nuclei of all normal tissues. SMARCB1 gene inactivation has been implicated in the pathogenesis of a diverse group of malignant neoplasms that tend to share "rhabdoid" cytomorphology. This group of SMARCB1-deficient tumors is now further expanded by a subset of carcinomas arising in the sinonasal tract. SMARCB1 immunostaining was performed on 142 sinonasal carcinomas. Tumors that showed loss of expression were further characterized for SMARCB1 deletions by fluorescence in situ hybridization. Nine of 142 (6%) primary sinonasal carcinomas showed loss of SMARCB1 expression by immunohistochemistry. Five patients were women, and patients ranged in age from 33 to 78 years (mean 59 y). The SMARCB1-deficient tumors were characterized by nests, sheets, and cords of cells without any histologic evidence of specific (eg, squamous or glandular) differentiation. The tumors comprised varying proportions of basaloid and rhabdoid cells. The SMARCB1-deficient carcinomas had been diagnosed as nonkeratinizing squamous cell carcinomas (n=3), sinonasal undifferentiated carcinomas (n=2), myoepithelial carcinoma (n=2), nonintestinal adenocarcinoma (n=1), and carcinoma, not otherwise specified (n=1). Fluorescence in situ hybridization analysis revealed SMARCB1 deletions in 6 of 8 (75%) carcinomas. The SMARCB1-deficient carcinomas did not harbor human papillomavirus or NUT-1 alterations. Six patients presented with T4 disease, 5 patients developed local recurrences and/or distant metastases, and 4 died of their disease. Inactivation of the SMARCB1 tumor-suppressor gene appears to be involved in the pathogenesis of a subset of sinonasal carcinomas, further expanding the family of SMARCB1-deficient neoplasms and further delineating a bewildering group of poorly/undifferentiated, aggressive carcinomas arising at this site. The ability to detect SMARCB1 loss by immunohistochemistry, particularly when dealing with poorly differentiated carcinomas with basaloid or rhabdoid features, should facilitate a more comprehensive understanding of these sinonasal carcinomas including clinical behavior and response to targeted therapies.
authors.affiliation: Departments of *Pathology †Otolaryngology/Head and Neck Surgery §Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD ‡Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Bishop
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Antonescu
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000172:deficiency* / Q000235:genetics; D001706:Biopsy; D002277:Carcinoma / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000556:secondary / Q000628:therapy; D002467:Cell Nucleus / Q000737:chemistry; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010255:Paranasal Sinus Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D010256:Paranasal Sinuses / Q000737:chemistry* / Q000473:pathology; D000071796:SMARCB1 Protein; D013997:Time Factors; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors