title: Aberrant nuclear/cytoplasmic localization and gene mutation of beta-catenin in classic pulmonary blastoma: beta-catenin immunostaining is useful for distinguishing between classic pulmonary blastoma and a blastomatoid variant of carcinosarcoma.
abstract: It is now known that gene mutation of beta-catenin with subsequent nuclear/cytoplasmic (N/C) overaccumulation of the protein plays an important role in tumorigenesis of various organs. We recently demonstrated that low-grade adenocarcinoma of the fetal lung type (L-FLAC)/well-differentiated fetal adenocarcinoma (WDFA), the epithelial prototype of classic pulmonary blastoma (CPB), shows N/C localization of beta-catenin with genetic mutation. This prompted us to further investigate the state of beta-catenin abnormality in CPB and related neoplasms. We studied 9 lung tumors previously diagnosed as biphasic pulmonary blastoma (PB). Histologically, 4 cases (median age 34 years) were CPB with l-FLAC/WDFA as the epithelial component, whereas 5 cases (median age 65 years) were a variant of carcinosarcoma with high-grade FLAC/clear cell adenocarcinoma with fetal lung features as the epithelial component, which we term the blastomatoid variant of carcinosarcoma (BCS). Immunohistochemically, all 4 CPBs showed aberrant N/C localization of beta-catenin both in the epithelial and mesenchymal components, with especially high staining intensity in the budding glands and morules. In contrast, all 5 BCSs showed preserved or diminished membranous expression and no significant N/C expression of beta-catenin in the epithelial component, and absent or focal N/C expression of beta-catenin in the mesenchymal component. Mutational analysis of exon 3 of the beta-catenin gene revealed that 3 CPBs harbored missense mutations (S29F, S37F, and S37F), whereas none of the 5 BCSs had this mutation. This study suggests that beta-catenin gene mutations may play a role in the tumorigenesis of CPB. Although CPB and BCS have often been grouped together as biphasic PB, they are different entities based on immunohistochemical and molecular analysis of beta-catenin. Immunostaining for beta-catenin is useful for the discrimination.
authors.affiliation: Department of Pathology, Yokohama City University Medical Center, Yokohama, Japan. nakatani@faculty.chiba-u.jp
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
authors.forename: Tamiko
authors.initials: T
authors.lastname: Takemura
authors.forename: Teruaki
authors.initials: T
authors.lastname: Oka
authors.forename: Toyoharu
authors.initials: T
authors.lastname: Yokoi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takagi
authors.forename: Shigeo
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Kenji
authors.initials: K
authors.lastname: Kashima
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hara
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamada
authors.forename: Akinori
authors.initials: A
authors.lastname: Nozawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Inayama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Nobuo
authors.initials: N
authors.lastname: Ogawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kitamura
authors.forename: Milan
authors.initials: M
authors.lastname: Resl
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Cho
authors.forename: Michael N
authors.initials: MN
authors.lastname: Koss
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Mark
mesh_terms: D000328:Adult; D000368:Aged; D002296:Carcinosarcoma / Q000473:pathology; D002467:Cell Nucleus / Q000737:chemistry*; D003593:Cytoplasm / Q000737:chemistry*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018202:Pulmonary Blastoma / Q000235:genetics* / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics*; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin