Alteration of the p53 gene of lung carcinomas with sarcomatous transformation (spindle cell carcinoma): analysis of four cases.

Abstract

Lung carcinoma with sarcomatous transformation (LCST) is highly aggressive and characterized by local invasion and/or distant metastasis, which leads to a shorter survival than ordinary lung carcinomas. Therefore, to elucidate whether the malignant potential of the spindle cell element in LCST is associated with the alteration of the p53 gene, four cases were examined by analyses of overexpression of the p53 oncoprotein, mutation of the p53 gene and loss-of-heterozygosity (LOH) at chromosome 17p. In two cases overexpression of the p53 oncoprotein of the spindle cell component showed a higher degree of staining than that of the carcinoma component; LOH was identified in both carcinoma and sarcomatous components in one case, while in contrast, another case showed LOH in the sarcomatous component only. Mutations were clearly detected in two cases; one showed a CTT to CGT transversion in codon 194 of exon 6 in both components, whereas the other showed a CTG to CAG transversion in codon 265 of exon 8 in the sarcomatous component only. On the basis of these observations, it suggested that the sarcomatous component shows a higher frequency of p53 gene abnormalities in comparison to the carcinoma component. These results also suggested that the acquisition of malignant potential in the sarcomatous component, or the morphological alteration of carcinoma cells, is correlated with abnormalities associated with the p53 gene.