title: β-catenin (CTNNB1) S33C mutation in ovarian microcystic stromal tumors.
abstract: Microcystic stromal tumor (MCST) is a recently described subtype of ovarian tumor characterized by prominent microcystic histologic pattern and diffuse immunoreactivity for CD10 and vimentin. However, its pathobiology, particularly its histogenesis, remains largely unclear. Here, we report 2 cases of ovarian MCST, in which we have performed extensive histologic, immunohistochemical, and genetic investigations to determine its distinct nature among ovarian neoplasms. The patients were 32 and 41 years of age. Both tumors were solid and cystic masses involving the right ovary. Microscopically, tumor cells with generally bland, round-to-ovoid nuclei grew in microcystic, macrocystic, and solid patterns. Intervening thick fibrous stroma was observed. Immunohistochemically, tumor cells were diffusely and strongly positive for CD10, vimentin, and Wilms tumor 1. Furthermore, we detected aberrant nuclear expression of β-catenin protein in both cases. Of interest, mutation analyses revealed the presence of an identical point mutation, c.98C>G, in exon 3 of β-catenin (CTNNB1) in both tumors. This is an oncogenic mutation that causes replacement of serine with cysteine at codon 33, leading to the loss of a phosphorylation site in the β-catenin protein. The results of this study strongly suggest that dysregulation of the Wnt/β-catenin pathway plays a fundamental role in the pathogenesis of ovarian MCST. Finally, by comparing the immunophenotype of MCST with its histologic mimics and other ovarian sex cord-stromal tumors, we were able to identify unique features of MCST and a panel of markers useful in differential diagnosis.
authors: Department of Pathology, Graduate School of Medicine, The University of Tokyo, Japan.
authors: Daichi
authors: D
authors: Maeda
authors: Junji
authors: J
authors: Shibahara
authors: Takahiko
authors: T
authors: Sakuma
authors: Masanori
authors: M
authors: Isobe
authors: Shinichi
authors: S
authors: Teshima
authors: Masaya
authors: M
authors: Mori
authors: Katsutoshi
authors: K
authors: Oda
authors: Shunsuke
authors: S
authors: Nakagawa
authors: Yuji
authors: Y
authors: Taketani
authors: Shumpei
authors: S
authors: Ishikawa
authors: Masashi
authors: M
authors: Fukayama
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D015260:Neprilysin / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017354:Point Mutation; D000072260:RNA Splicing Factors; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D014746:Vimentin / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; D014746:Vimentin; C419554:WTAP protein, human; D051176:beta Catenin; D015260:Neprilysin