Role of p53 gene mutations in human esophageal carcinogenesis: results from immunohistochemical and mutation analyses of carcinomas and nearby non-cancerous lesions.
نویسندگان
چکیده
In order to characterize p53 alterations in esophageal cancer and to study their roles in carcinogenesis, we performed gene mutation and immunohistochemical analysis on 43 surgically resected human esophageal specimens, which contain squamous cell carcinoma (SCC) and adjacent non-cancerous lesions, from a high-incidence area of Linzhou in Henan, China. A newly developed immunohisto-selective sequencing (IHSS) method was used to enrich the p53 immunostain-positive cells for mutation analysis. p53 gene mutations were detected in 30 out of 43 (70%) SCC cases. Among 29 SCC cases that were stained positive for p53 protein, 25 (86%) were found to contain p53 mutations. In five cases of SCC with homogeneous p53 staining, the same mutation was observed in samples taken from four different positions of each tumor. In a well differentiated cancer nest, p53 mutation was detected in only the peripheral p53-positive cells. In tumor areas with heterogeneous p53 staining, either the area stained positive for p53 had an additional mutation to the negatively stained area or both areas lacked any detectable p53 mutation. In the p53-positive non-cancerous lesions adjacent to cancer, p53 mutations were detected in seven out of 16 (47%) samples with basal cell hyperplasia (BCH), eight out of 12 (67%) samples with dysplasia (DYS), and six out of seven (86%) samples with carcinoma in situ (CIS). All mutations found in lesions with DYS and CIS were the same as those in the nearby SCC. In seven cases of BCH containing mutations, only three had the same mutations as the nearby SCC. The results suggest that p53 mutation is an early event in esophageal carcinogenesis occurring in most of the DYS and CIS lesions, and cells with such mutations will progress to carcinoma, whereas the role of p53 mutations in BCH is less clear.
منابع مشابه
New p53 Gene Mutation in non-Cancerous Mustard Gas Exposed Lung
Objective Mustard gas (MG) is a poisoning chemical, mutagenic and carcinogenic alkylating agent. It is used during World War I and also Iran-Iraq conflict. The p53 tumor suppressor gene is involved in the pathogenesis of malignant disease. The aim of this study is to determine possible mutation in p53 gene of lung sample from mustard gas exposed patients. Material and Methods Twelve lung bio...
متن کاملMutations of p53 Gene in Skin Cancers: a Case Control Study
Background: The most frequently mutated tumor suppressor gene found in human cancer is p53. In a normal situation, p53 is activated upon the induction of DNA damage to either arrest the cell cycle or to induce apoptosis. However, when mutated, p53 is no longer able to properly accomplish these functions. The aim of this study was to investigate the expression of p53 gene in cases of skin cancer...
متن کاملLack of Mutation in the Hot Spot Region of the Human P53 Gene in a Number of Iranian Hepatocellular Carcinoma Patients
Objectives and Background: Mutation directed inactivation of the tumor suppressor gene p53 have been found incountries with high frequency for hepatocellular carcinomas (HCCs). Our goal in the present study was screening of the p53 gene in tumor tissues from HCC affected individuals in southwest Iran for putative mutations in exons 7 and 8 that are known as hot spot regions. Materials & Met...
متن کاملThe Prevalence of P53 Mutations in Laryngeal Cancer in Kerman
Background &Aims: Laryngeal cancer is the second common cancer of respiratory tract, following the lung cancer. Carcinogenesis is a complex multistage process; molecular genetics has provided the evidence that activation of proto-oncogene and loss or inactivation of tumor suppressor genes (TSG) are involved in a large number of malignancies. One of the earliest significant tumor suppressor gene...
متن کاملمقایسه شیوع جهشهای ژنتیکی در ژنهای APC و P53 در پولیپهای آدنومایی کولون از نوع دیسپلازی خفیف با نوع شدیدCorrelation of Mutations Prevalence in P53 and APC in Low Grade and High Grade Colonic Adenomatous Polyps
Background & Aim: Colorectal polyps are among the commonest lesions encountered by surgical pathologist. In the United States, colonoscopy and flexible sigmoidoscopy are recommended for almost all people over the age of 40 years. The development of carcinoma from adenomatous lesions is referred to as the adenoma-carcinoma sequence. Virtually, all colorectal carcinomas exhibit genetic altera...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Carcinogenesis
دوره 20 4 شماره
صفحات -
تاریخ انتشار 1999