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 investigated its genetic status, protein expression and its role in apoptosis in samples of complete and partial hydatidiform mole as compared with those of normal placenta. Direct sequencing of polymerase chain reaction (PCR) products of the coding and non-coding regions of the p53 gene demonstrated no mutations in any of the studied samples. Immunohistochemical studies revealed increased expression of the p53 protein predominantly in the nuclei of villous 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 staining intensity and pattern was observed. An in situ detection of DNA nicking (TUNEL) staining, demonstrating apoptosis, was also detected predominantly in villous cytotrophoblasts and in stromal areas. The per centage of apoptotic cells in all studied samples, determined by flow cytometry, demonstrated 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 apoptosis to modulate excessive trophoblastic proliferation.
Halperin
R
R
Department of Obstetrics and Gynecology, Assaf Harofeh Medical Center, Zerifin, Israel.
Peller
S
S
Sandbank
J
J
Bukovsky
I
I
Schneider
D
D
D017209:Apoptosis; D001483:Base Sequence; D016022:Case-Control Studies; D053938:DNA Fragmentation; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression; D016158:Genes, p53; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020287:In Situ Nick-End Labeling; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
D017931:DNA Primers; D016159:Tumor Suppressor Protein p53