Alterations of p53, cyclin D1 and pRB expression in the carcinogenesis of esophageal squamous cell carcinoma.
Many molecular alterations occur in esophageal carcinogenesis; however, little is known about the molecular genetic events responsible for the development of carcinoma. We investigated the expression of ki67, p53, cyclin D1 and pRB in 105 biopsy specimens using immunohistochemistry from iodine unstained lesions as indicators of carcinogenesis of the esophagus. Also, the genetic alternation of esophageal dysplasia from patients with accompanying esophageal squamous cell carcinoma (ESCC) was examined to study the evidence for field carcinogenesis in the esophagus. The expression of p53, cyclin D1 and pRB was detected in 31, 0 and 51.7% respectively of mild dysplasia; 40, 0 and 70% of moderate dysplasia; 40, 20 and 70% of severe dysplasia; and 48, 32 and 80% of carcinoma specimens. p53 expression was significantly increased in mild dysplasia, whereas cyclin D1 and pRB expression were significantly increased in carcinoma as compared to both normal epithelium and esophagitis. The ki67 LI and the rate of p53 expression were significantly higher in dysplasia with ESCC than in dysplasia without ESCC. Ki67, p53, cyclin D1 and pRB expression may be useful biomarkers for assessing the risk of developing esophageal cancer. Dysplasia observed at screening for secondary lesions has a highly malignant potential and careful follow-up studies are required.
Kawakubo
H
H
Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Ozawa
S
S
Ando
N
N
Kitagawa
Y
Y
Mukai
M
M
Ueda
M
M
Kitajima
M
M
D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D019938:Cyclin D1 / Q000096:biosynthesis; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology*; D004941:Esophagitis / Q000378:metabolism / Q000473:pathology; D004947:Esophagus / Q000737:chemistry / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1