title: Aberrant TP53 detected by combining immunohistochemistry and DNA-FISH improves Barrett's esophagus progression prediction: a prospective follow-up study.
abstract: Barrett's esophagus (BE) goes through a sequence of low grade dysplasia (LGD) and high grade dysplasia (HGD) to esophageal adenocarcinoma (EAC). The current gold standard for BE outcome prediction, histopathological staging, can be unreliable. TP53 abnormalities may serve as prognostic biomarkers. TP53 protein accumulation detected by immunohistochemistry (IHC) indirectly assesses TP53 mutations. DNA fluorescent in situ hybridization (FISH) on brush cytology specimens directly evaluates gene locus loss. We evaluated if IHC and FISH are complementary tools to assess TP53 abnormalities and tested their prognostic value in a long-term prospective follow-up of a BE cohort. TP53 IHC on tissue sections and FISH on brush cytology specimens were evaluated for 116 BE patients with respect to the different histological stages. The TP53 abnormalities were further studied in a panel of cell lines representative of the Barrett's carcinogenic sequence. For 91patients, the predictive value of TP53 abnormalities with respect to progression to HGD/EAC was tested after long term follow-up. The frequency of IHC and FISH TP53 abnormalities increased significantly with increasing histological stage (P < 0.001, Chi(2) -test). Combining the techniques detected TP53 abnormalities in 100% of patients with LGD, HGD, and EAC. Multivariate analysis showed that IHC (hazard ratio: 17, 95% CI: 3.2-96, P = 0.001) and FISH (hazard ratio: 7.3, 95% CI: 1.3-41, P = 0.02) were both independent significant predictors of progression. Combining FISH and IHC in assessing TP53 abnormalities leads to an increased detection rate of TP53 aberrations and improved accuracy for predicting BE progression.
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands; Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Akueni L
authors.initials: AL
authors.lastname: Davelaar
authors.forename: Silvia
authors.initials: S
authors.lastname: Calpe
authors.forename: Liana
authors.initials: L
authors.lastname: Lau
authors.forename: Margriet R
authors.initials: MR
authors.lastname: Timmer
authors.forename: Mike
authors.initials: M
authors.lastname: Visser
authors.forename: Fiebo J
authors.initials: FJ
authors.lastname: Ten Kate
authors.forename: Kaushal B
authors.initials: KB
authors.lastname: Parikh
authors.forename: Sybren L
authors.initials: SL
authors.lastname: Meijer
authors.forename: Jacques J
authors.initials: JJ
authors.lastname: Bergman
authors.forename: Paul
authors.initials: P
authors.lastname: Fockens
authors.forename: Kausilia K
authors.initials: KK
authors.lastname: Krishnadath
mesh_terms: D000368:Aged; D001471:Barrett Esophagus / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002460:Cell Line; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53