title: Programmed cell death 4 nuclear loss and miR-21 or activated Akt overexpression in esophageal squamous cell carcinogenesis.
abstract: The programmed cell death 4 (PDCD4) tumor suppressor is down-regulated in several malignancies, and the (subcellular) expression of its protein product is modulated by both oncomiR miR-21 and protein kinase B (Akt). PDCD4 and activated Akt (phosphorylated Akt [pAkt]) expression were assessed immunohistochemically in 53 tissue samples obtained from 25 endoscopic esophageal mucosal resections performed for squamous intraepithelial neoplasia (IEN) or squamous intramucosal carcinoma (IM-SSC). In total, 33 IEN (low-grade = 15; high-grade = 15) and 20 IM-SSC specimens were considered; 50 additional tissue samples of histologically proven normal esophageal mucosa were considered as normal controls. To further validate the results achieved, miR-21 expression (as assessed by quantitative real-time polymerase chain reaction and in situ hybridization) was tested in another series of 15 normal esophageal tissue samples, 15 high-grade IEN, and 15 IM-SCCs. Normal suprabasal squamous epithelial layers consistently featured strong PDCD4 nuclear immunostaining, which was significantly lower (P < 0.001) in IEN (both low-and high-grade) and in IM-SSC. Conversely, pAkt and miR-21 expression was significantly up-regulated in the whole spectrum of preneoplastic/neoplastic lesions considered. PDCD4 down-regulation, as assessed by immunohistochemistry, is a reliable biomarker of early-stage squamous cell esophageal neoplasia, providing additional information in the histological assessment of these lesions.
authors: Department of Medical Diagnostic Sciences and Special Therapies, Surgical Pathology and Cytopathology Unit, University of Padova, Italy.
authors: M
authors: M
authors: Fassan
authors: S
authors: S
authors: Realdon
authors: M
authors: M
authors: Pizzi
authors: M
authors: M
authors: Balistreri
authors: G
authors: G
authors: Battaglia
authors: G
authors: G
authors: Zaninotto
authors: E
authors: E
authors: Ancona
authors: M
authors: M
authors: Rugge
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002278:Carcinoma in Situ / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012189:Retrospective Studies; D018709:Statistics, Nonparametric
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; D051057:Proto-Oncogene Proteins c-akt