Analysis of mutant p53 and telomerase activity in non-small cell lung cancer.
The number of mutant p53 protein-positive tumor cells in primary non-small cell lung carcinoma (NSCLC) cases were quantitated by flow cytometry (FCM) and the relationships of these data to various factors were evaluated. Furthermore, the method of quantitating telomerase activity was investigated. Forty patients with primary lung carcinoma encountered between December 1995 and December 1997 were investigated. Among these cases, telomerase activity was measured. Using PAb421, cells were reacted with fluorescent antibody and fluorescence was quantitated by FCM. Fluorescence index (FI) was estimated in relation to the positivity rates of negative controls and were quantitatively evaluated. FI values of normal lung tissue were obtained from normal lung tissue excised from young patients with pulmonary bulla. Values that were 2SD or more above the mean value of normal lung tissue (> 2.19) were regarded as mutant p53-positive, and 14 (35.0%) of 40 lung carcinoma cases were positive by this criterion. Of 13 poorly differentiated carcinoma cases, seven cases (53.8%) were positive, which was significantly high. Furthermore, the telomerase activity was converted to numerical values in 40 cases using the telomelic repeat amplication protocol (TRAP) method as well as the total product generated (TPG) method. The mean TPG value of the 40 cases was 75.21 +/- 15.63. Among these cases, the mean value of fourteen p53-positive cases was 124.49 +/- 37.19, which was higher than that of 26 negative cases, 48.68 +/- 10.88, showing a significant difference. The method used in this study was considered a useful method that allows accurate and objective evaluation of mutant p53 expression. It was suggested that mutant p53 expression may affect the degree of tumor cell differentiation. Consequently, it was confirmed in this study that mutant p53 expression and telomerase activity were closely associated in lung cancer.
Kiyooka
K
K
Department of Surgery, Division II, Kobe University School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017.
Maniwa
Y
Y
Okada
M
M
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000235:genetics* / Q000601:surgery; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D016158:Genes, p53 / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D012016:Reference Values; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000378:metabolism*
D014408:Biomarkers, Tumor; D019098:Telomerase