title: Loss of SMARCA4 Expression Is Both Sensitive and Specific for the Diagnosis of Small Cell Carcinoma of Ovary, Hypercalcemic Type.
abstract: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare ovarian neoplasm that occurs in young women and has a poor prognosis. The histologic diagnosis of SCCOHT can be challenging due to its rarity and relatively nonspecific histologic features, which range from the classic, first-described small cell morphology to a pattern in which there are large cells with abundant eosinophilic cytoplasm. Many entities can be in the differential diagnosis and to date, immunohistochemical stains have shown no distinctive profile and have been of limited aid. SMARCA4 (also known as BRG1) mutations have recently been reported at high frequency in these tumors. SMARCA4 is an important component of the SWI/SNF complex that regulates gene expression through alteration of nucleosome conformation. Studies to date have suggested that immunohistochemical loss of expression of SMARCA4 is associated with the presence of a SMARCA4 mutation in most cases. In this study, the sensitivity and specificity of the immunohistochemical loss of SMARCA4 expression for the diagnosis of SCCOHT is examined in the context of the differential diagnosis with other primary or metastatic ovarian tumors. All but one of the SCCOHT showed loss of SMARCA4 expression (16/17; 94%), while of 279 other tumors tested, only two tumors (one clear cell carcinoma and one ovarian melanoma) showed loss of SMARCA4 expression. We conclude that SMARCA4 immunohistochemistry is highly sensitive and specific for a diagnosis of SCCOHT and is of clinical utility in the differential diagnosis of poorly differentiated ovarian tumors.
authors.affiliation: Departments of *Pathology ‡Surgery, Memorial Sloan Kettering Cancer Center §Department of Pathology, Stony Brook University Medical Center, New York, NY †Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Niamh
authors.initials: N
authors.lastname: Conlon
authors.forename: Annacarolina
authors.initials: A
authors.lastname: Silva
authors.forename: Esther
authors.initials: E
authors.lastname: Guerra
authors.forename: Petar
authors.initials: P
authors.lastname: Jelinic
authors.forename: Brooke A
authors.initials: BA
authors.lastname: Schlappe
authors.forename: Narciso
authors.initials: N
authors.lastname: Olvera
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Mueller
authors.forename: Carmen
authors.initials: C
authors.lastname: Tornos
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.forename: Robert H
authors.initials: RH
authors.lastname: Young
authors.forename: Esther
authors.initials: E
authors.lastname: Oliva
authors.forename: Douglas
authors.initials: D
authors.lastname: Levine
authors.forename: Robert A
authors.initials: RA
authors.lastname: Soslow
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D018288:Carcinoma, Small Cell / Q000201:enzymology* / Q000473:pathology; D002454:Cell Differentiation; D004265:DNA Helicases / Q000032:analysis*; D003937:Diagnosis, Differential; D015536:Down-Regulation; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000201:enzymology* / Q000473:pathology; D007150:Immunohistochemistry; D009687:Nuclear Proteins / Q000032:analysis*; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D014157:Transcription Factors / Q000032:analysis*; D014481:United States
chemical_list: D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases