Expression of the p53 gene and apoptosis in gestational trophoblastic disease

In order to understand the involvement of the p53 tumour suppressor gene in the pathogenesis of gestational trophoblastic disease (GTD), we investigat ed its genetic status, protein expression and its role in apoptosis in samp les of complete and partial hydatidiform mole as compared with those of nor mal placenta. Direct sequencing of polymerase chain reaction (PCR) products of the coding and non-coding regions of the p53 gene demonstrated no mutat ions in any of the studied samples. Immunohistochemical studies revealed in creased expression of the p53 protein predominantly in the nuclei of villou s cytotrophoblasts. This over-expression of p53 was found in all samples of complete mole, in 50 per cent of partial mole samples and in about 30 per cent of normal placenta cases, although no significant difference in the st aining intensity and pattern was observed. An in situ detection of DNA nick ing (TUNEL) staining, demonstrating apoptosis, was also detected predominan tly in villous cytotrophoblasts and in stromal areas. The per centage of ap optotic cells in all studied samples, determined by flow cytometry, demonst rated a significant increase in apoptotic cells in samples of complete and partial hydatidiform mole compared with those of normal placenta (P<0.0003 and P<0.004 respectively). In conclusion, the current study may provide a possible explanation to the pathogenesis of GTD, probably associated with extensive p53-dependent apopt osis to modulate excessive trophoblastic proliferation. (C) 2000 Harcourt P ublishers Ltd.