title: Ovarian small cell carcinoma of hypercalcemic type - evidence of germline origin and SMARCA4 gene inactivation. a pilot study.
abstract: Ovarian tumors from two patients, compatible by histological and immunohistochemical criteria with small cell carcinoma of hypercalcemic type (SCCHT) (WT1+, EMA dispersed+, synaptophysin+ or dispersed+), were extensively sampled in order to find clues to their histogenesis. Subsequently, small foci of immature teratoma were found in both of them (in 1/122 and in 3/80 tumor sections). In one case, microfoci of yolk sac tumor were also present within the teratoma area as well as in the background of the small cell tumor population - in the primary tumor and in omental metastasis. We found a resemblance of the microscopic patterns of SCCHT and atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system, and this prompted us to evaluate INI-1 and SMARCA4 immunohistochemical expression, because their alternative loss is regarded as a molecular hallmark of AT/RT. INI-1 expression was retained, while that of SMARCA4 was lost. We therefore analyzed tumor DNA by PCR amplification and sequencing for mutations in the SMARCA4 gene (NG_011556.1), which were identified in both tumors (c.2184_2206del; nonsense c.3277C>T - both in one tumor; nonsense c.3760G>T in another tumor). These data suggest that SCCHT is most likely an embryonal tumor originating from immature teratoma and related to malignant rhabdoid tumor. Further analyses are necessary to determine whether the tumors diagnosed as SCCHT constitute a homogeneous group or represent more than one entity.
authors.affiliation: Jolanta Kupryjańczyk MD, PhD, Department of Pathology, The Maria Sklodowska-Curie, Memorial Cancer Centre and Institute of Oncology, Roentgena 5, 02-781 Warsaw, Poland, tel. +48 22 546 27 26, fax +48 22 546 21 81, e-mail: jkupry@coi.waw.pl.
authors.forename: J
authors.initials: J
authors.lastname: Kupryjańczyk
authors.forename: A
authors.initials: A
authors.lastname: Dansonka-Mieszkowska
authors.forename: J
authors.initials: J
authors.lastname: Moes-Sosnowska
authors.forename: J
authors.initials: J
authors.lastname: Plisiecka-Hałasa
authors.forename: L
authors.initials: L
authors.lastname: Szafron
authors.forename: A
authors.initials: A
authors.lastname: Podgórska
authors.forename: I K
authors.initials: IK
authors.lastname: Rzepecka
authors.forename: B
authors.initials: B
authors.lastname: Konopka
authors.forename: A
authors.initials: A
authors.lastname: Budziłowska
authors.forename: A
authors.initials: A
authors.lastname: Rembiszewska
authors.forename: W
authors.initials: W
authors.lastname: Grajkowska
authors.forename: B
authors.initials: B
authors.lastname: Spiewankiewicz
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D018095:Germ-Line Mutation; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D010865:Pilot Projects; D011247:Pregnancy; D011446:Prospective Studies; D018335:Rhabdoid Tumor / Q000235:genetics / Q000473:pathology; D017422:Sequence Analysis, DNA; D013724:Teratoma / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D009687:Nuclear Proteins; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases