DETECTION OF CELLULAR HETEROGENEITY BY DNA-PLOIDY, 17-CHROMOSOME, ANDP53 GENE IN PRIMARY-CARCINOMA AND METASTASIS IN A CASE OF OVARIAN-CANCER

An unusual case of a patient with ovarian carcinoma carrying the p53 p oint mutation in both metastases (omentum and lymph node), but not in the primary tumor, is described. The presence of a p53 single mutation (G:A) at the second base of codon 248 was examined by polymerase chai n reaction-amplification refractory mutation system (PCR-ARMS) analysi s. This case was examined also by fluorescent in situ hybrization (FIS H) analysis and flow cytometry (FCM) to obtain further information at the single cell level and to detect heterogeneity within a population of cells. FCM analysis evidenced the same multiple aneuploid cell subp opulations in primary and in metastatic samples showing the presence o f a cellular heterogeneity. FISH analysis showed a disomic condition f or the 17 chromosome in the primary and in one metastasis, while in th e other metastasis a monosomic together with a disomic subpopulation w as revealed. Our results confirm the independent clonal evolution of t he metastasis. The late mutation event observed only in metastatic spe cimens suggests the hypothesis that in the primary tumor the wild-type gene either does not perform its control role for unknown genetic str uctural events or the p53 gene in this case does not play a critical r ole in carcinogenesis.