title: Reduced Fhit expression occurs in the early stage of esophageal tumorigenesis: no correlation with p53 expression and apoptosis.
abstract: The FHIT gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumor suppressor gene involved in multiple tumors, including esophageal carcinoma. We analyzed Fhit expression using an immunohistochemical method in invasive carcinoma, carcinoma in situ (CIS) and dysplasia, in paraffin sections of 75 esophageal squamous cell carcinomas (ESCs) to further elucidate the role of Fhit protein in esophageal carcinogenesis. In addition, we also examined whether Fhit expression correlated with p53 expression and apoptosis. Compared to adjacent normal mucosa, significant loss or reduction of Fhit expression was noted in 67 of 75 (89.3%) invasive ESCs, in 13 of 19 (68.4%) CIS lesions, and in 10 of 23 (43.5%) dysplastic lesions. There was a progressive loss or reduction of Fhit expression with progressive increases in the severity of histopathological changes (p < 0.001). However, there was no association between Fhit expression and clinicopathological findings, including tumor stage, lymph node metastasis, or overall survival. Moreover, Fhit expression was not significantly associated with p53 expression and apoptosis. These results indicate that abnormal Fhit expression is a common event in the early stage of ESC development and may occur independently of p53 expression and apoptosis mechanisms.
authors.affiliation: Second Department of Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kitamura
authors.forename: K
authors.initials: K
authors.lastname: Yashima
authors.forename: E
authors.initials: E
authors.lastname: Okamoto
authors.forename: H
authors.initials: H
authors.lastname: Andachi
authors.forename: A
authors.initials: A
authors.lastname: Hosoda
authors.forename: Y
authors.initials: Y
authors.lastname: Kishimoto
authors.forename: G
authors.initials: G
authors.lastname: Shiota
authors.forename: H
authors.initials: H
authors.lastname: Ito
authors.forename: N
authors.initials: N
authors.lastname: Kaibara
authors.forename: H
authors.initials: H
authors.lastname: Kawasaki
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002278:Carcinoma in Situ / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018450:Disease Progression; D004790:Enzyme Induction; D004847:Epithelial Cells / Q000201:enzymology; D004935:Esophageal Diseases / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004947:Esophagus / Q000201:enzymology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000201:enzymology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D011230:Precancerous Conditions / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D000099170:Bis(5'-adenosyl)triphosphatase