title: Genetic alteration and immunohistochemical staining patterns of ovarian high-grade serous adenocarcinoma with special emphasis on p53 immnnostaining pattern.
abstract: We evaluated p53, KRAS, BRAF and CTNNB1 mutation and p53, WT1, p16 and beta-catenin expression in 31 ovarian high-grade serous adenocarcinoma. Twenty-five (80.6%) tumors contained functional mutations of p53; three frameshift, four nonsense and 19 missense mutations. None of the tumors showed KRAS, BRAF or CTNNB1 mutation. In all 18 tumors with missense mutations, ≥60% of tumor cells were strongly positive for p53 immunostaining whereas all tumors with frameshift or nonsense mutations were completely negative. Missense mutation was correlated with diffuse and strong imunoreaction and frameshift/nonsense mutation was correlated with completely negative immunoreaction (P = 0.000). Tumors with wild-type p53 revealed a wide range of immunostaining patterns. In 27 (87.1%) and 18 (58.1%) tumors, ≥50% of tumor cells were moderate to strongly positive for WT1 and p16, respectively. A considerable intratumoral heterogeneity for p16 expression was present. None of the tumors demonstrated nuclear beta-catenin expression. p53 mutations appear to be a powerful molecular marker for ovarian high-grade serous adenocarcinoma. Using p53 with an appropriate interpretation criteria together with WT1, p16 and beta-catenin, most of the high-grade serous adenocarcinoma could be distinguished from other ovarian tumors.
authors.affiliation: Department of Pathology, Konkuk University School of Medicine, Seoul 143-729, Republic of Korea.
authors.forename: Sang Hwa
authors.initials: SH
authors.lastname: Lee
authors.forename: Hyunkyung
authors.initials: H
authors.lastname: Kim
authors.forename: Wook Youn
authors.initials: WY
authors.lastname: Kim
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Han
authors.forename: So Dug
authors.initials: SD
authors.lastname: Lim
authors.forename: Wan Seop
authors.initials: WS
authors.lastname: Kim
authors.forename: Sehun
authors.initials: S
authors.lastname: Kim
authors.forename: Tae Sook
authors.initials: TS
authors.lastname: Hwang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D018389:Codon, Nonsense; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017931:DNA Primers / Q000235:genetics; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D056910:Republic of Korea; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D025721:WT1 Proteins / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; C495270:CTNNB1 protein, human; D018389:Codon, Nonsense; D019941:Cyclin-Dependent Kinase Inhibitor p16; D017931:DNA Primers; D004273:DNA, Neoplasm; C117307:KRAS protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D025721:WT1 Proteins; C583751:WT1 protein, human; D051176:beta Catenin; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins