K Oka1, Y Suzuki, T Nakano. 1. Division of Radiation Medicine, Research Center of Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
Abstract
BACKGROUND: The p27/Kip1 gene inhibits a variety of cyclin-cyclin-dependent kinase complexes and regulates cell growth. The p53 gene acts as a tumor suppressor gene, controlling entry into the S-phase of the cell cycle. METHODS: A total of 202 biopsy specimens obtained from 77 patients with squamous cell carcinoma of the cervix before and during radiotherapy (RT) was investigated for expression of p27 and p53 in conventionally fixed and processed histologic specimens using an immunohistochemical method. DNA samples exhibiting high p53 overexpression were analyzed for detection of the wild-type or mutant-type of p53 by polymerase chain reaction-single strand conformation polymorphism analysis. RESULTS: Carcinoma cells and degenerated or swollen carcinoma cells after RT that were positive for p27 and p53 showed intranuclear reactivity. Degenerated or swollen carcinoma cells after RT with 27 Gy showed stronger p53 positivity than carcinoma cells before RT. The mean p27 labeling index was decreased significantly after 27 Gy; conversely, the mean p53 labeling index was increased significantly after 27 Gy of RT. A high p27 labeling index before RT was associated significantly with good disease free and metastasis free survival. A high p53 labeling index before RT was associated with poor overall survival. Both samples examined before RT showed no mutations of p53 (exons 5-8). Four of 5 samples showed mutations in exon 5 or 7 of the p53 gene after 27 Gy of RT. CONCLUSIONS: The high p27 expression and low p53 expression in carcinoma cells before RT are regarded as predictive factors for good prognosis of patients with cervical squamous cell carcinoma treated with RT alone. The mean p27 and p53 indices change in an inverse fashion during the period between the initiation of RT and the period after 27 Gy of RT. RT induces the mutant-type p53 oncogene after 27 Gy. Copyright 2000 American Cancer Society.
BACKGROUND: The p27/Kip1 gene inhibits a variety of cyclin-cyclin-dependent kinase complexes and regulates cell growth. The p53 gene acts as a tumor suppressor gene, controlling entry into the S-phase of the cell cycle. METHODS: A total of 202 biopsy specimens obtained from 77 patients with squamous cell carcinoma of the cervix before and during radiotherapy (RT) was investigated for expression of p27 and p53 in conventionally fixed and processed histologic specimens using an immunohistochemical method. DNA samples exhibiting high p53 overexpression were analyzed for detection of the wild-type or mutant-type of p53 by polymerase chain reaction-single strand conformation polymorphism analysis. RESULTS:Carcinoma cells and degenerated or swollen carcinoma cells after RT that were positive for p27 and p53 showed intranuclear reactivity. Degenerated or swollen carcinoma cells after RT with 27 Gy showed stronger p53 positivity than carcinoma cells before RT. The mean p27 labeling index was decreased significantly after 27 Gy; conversely, the mean p53 labeling index was increased significantly after 27 Gy of RT. A high p27 labeling index before RT was associated significantly with good disease free and metastasis free survival. A high p53 labeling index before RT was associated with poor overall survival. Both samples examined before RT showed no mutations of p53 (exons 5-8). Four of 5 samples showed mutations in exon 5 or 7 of the p53 gene after 27 Gy of RT. CONCLUSIONS: The high p27 expression and low p53 expression in carcinoma cells before RT are regarded as predictive factors for good prognosis of patients with cervical squamous cell carcinoma treated with RT alone. The mean p27 and p53 indices change in an inverse fashion during the period between the initiation of RT and the period after 27 Gy of RT. RT induces the mutant-type p53 oncogene after 27 Gy. Copyright 2000 American Cancer Society.
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