Abnormal expression of CCND1 and RB1 in resection margin epithelia of lung cancer patients

被引:41
|
作者
Betticher, DC
Heighway, J
Thatcher, N
Hasleton, PS
机构
[1] CHRISTIE HOSP NHS TRUST, CRC, DEPT MED ONCOL, MANCHESTER M20 4BX, LANCS, ENGLAND
[2] UNIV HOSP BERN, CH-3010 BERN, SWITZERLAND
[3] CHRISTIE HOSP NHS TRUST, CRC, DEPT CANC GENET, PATERSON INST CANC RES, MANCHESTER M20 4BX, LANCS, ENGLAND
[4] WYTHENSHAWE HOSP, DEPT PATHOL, MANCHESTER M23 9LT, LANCS, ENGLAND
关键词
non-small-cell lung cancer; carcinogenesis; cyclin D1; CCND1; retinoblastoma protein; RB1; carcinoma in situ;
D O I
10.1038/bjc.1997.300
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Tumours develop through the accumulation of genetic alterations associated with a progressive increase of the malignant phenotype. In lung cancer, chronic exposure of bronchial epithelium to carcinogens in cigarette smoke may lead to multiple dysplastic and hyperplastic lesions scattered throughout the tracheobronchial tree. Little is known about the genetic alterations in such lesions. This study was carried out to examine cyclin D1 (CCND1) and retinoblastoma (RB1) gene expression in the bronchial epithelium of patients with lung cancer. Lung tumours and their corresponding tumour-free resection margins from 33 patients who underwent resection of non-small-cell lung cancer (NSCLC) were examined by immunostaining with monoclonal antibodies against cyclin D1 (DCS-6; Novocastra) and pRb (NCL Rb-l; Novocastra). Examination of the resection margins revealed four carcinomas in situ, 19 hyperplasias and ten sections showing apparently normal bronchial epithelium. A control group of patients, without lung tumours and who had never smoked, revealed no or weak cyclin D1 and positive pRb staining within bronchial epithelia. Increased cyclin D1 and diminished pRb expression were found in 76% (n = 25) and 27% (n = 9) of the resection margins respectively, and in 12% (n = 4) both cyclin D1 and pRb expression were altered. In the corresponding tumours, 48% (n = 16) were normal, while altered expression was found for cyclin D1 in 33% (n = 11), pRb in 27% (n = 9) and both in 9% (n = 3) of cases. It appears that altered expression of cyclin D1 and pRb is an early event in NSCLC development in almost half of cases analysed. Further investigations are needed to determine the significance of immunostaining of bronchial specimens in individuals at risk of lung cancer, with the possibility that the observations are of importance in the early diagnosis of NSCLC.
引用
收藏
页码:1761 / 1768
页数:8
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