title: Reduced expression of cytokeratin 4 and 13 is a valuable marker for histologic grading of esophageal squamous intraepithelial neoplasia.
abstract: Histologic evaluation of low-grade or high-grade intraepithelial neoplasia (LG-IN or HG-IN) of the esophagus is important for estimating the risk of progression to invasive carcinoma. Discrimination between LG-IN and HG-IN, or neoplasia and non-neoplastic lesion (NNL), however, is occasionally difficult. This study was designed to evaluate whether cytokeratin expression can be used for discrimination of these lesions. Esophageal Iodine-unstained lesions (n=154), less than 10 mm, were classified into HG-IN, LG-IN, and NNL. These lesions together with 154 foci of normal esophageal epithelium (NEE) were examined by immunohistochemistry for cytokeratins (CK4 and CK13), p53 overexpression, and the MIB-1 labeling index. The ratios of CK4- and CK13-positive staining were scored from 1 to 3. The CK4- and CK13-positive staining ratios were decreased in NNL (73% and 78%), LG-IN (55% and 69%), and HG-IN (33% and 48%), compared to NEE (91% and 95%). The differences between LG-IN and HG-IN, neoplasia and NNL, and among these three lesions and NEE were statistically significant (p < 0.005). The cytokeratin scores correlated with the MIB-1 labeling index (both: p < 0.0001), but not with p53 overexpression. CK4 and CK13 immunohistochemistry could be an objective method for evaluating the risk for progression to invasive carcinoma.
authors.affiliation: Department of Human Pathology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Takashima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kitagaki
authors.forename: Masaki
authors.initials: M
authors.lastname: Sekine
authors.forename: Tadatsune
authors.initials: T
authors.lastname: Iida
authors.forename: Kosuke
authors.initials: K
authors.lastname: Takemura
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Kawano
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Eishi
mesh_terms: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000032:analysis*; D002278:Carcinoma in Situ / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D018450:Disease Progression; D004847:Epithelial Cells / Q000473:pathology; D004848:Epithelium / Q000473:pathology; D004938:Esophageal Neoplasms / Q000473:pathology*; D004947:Esophagus / Q000473:pathology; D006801:Humans; D053535:Keratin-13 / Q000032:analysis*; D053527:Keratin-4 / Q000032:analysis*; D019394:Ki-67 Antigen / Q000032:analysis; D009092:Mucous Membrane / Q000473:pathology; D060787:Neoplasm Grading; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D053535:Keratin-13; D053527:Keratin-4; D019394:Ki-67 Antigen; C440408:MIB-1 antibody; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53