Hydatidiform moles result from abnormal fertilization and have been di
vided into partial and complete forms based on morphologic, cytogeneti
c, and clinical features, Little is known about their pathogenesis or
malignant transformation. We applied an immunohistochemical marker for
the p53 tumor suppressor gene product to placentas with hydropic chan
ge and hydatidiform moles to determine whether abnormal p53 gene produ
ct accumulation occurs in molar gestations, Ploidy of these placentas
was determined by now cytometry and fluorescence ka situ hybridization
. The mean percentages of p53-positive cells was determined by countin
g 200 cytotrophoblastic and proliferating trophoblastic cells. The sta
ining intensity tvas graded on a scale of 1+ (faint) to 3+ (strong). T
he mean percentage of p53-positive cells for the placentas were as fol
lows: 8.9% +/- 10.5 for hydropic change; 28.0% +/- 13.2 for partial mo
le; and 41.0% +/- 19.6 for complete mole. There was a significant diff
erence in p53 expression between hydropic change and partial mole (P =
0.05) and hydropic change and complete mole (P = 0.0008). Although th
ere was a difference between partial mole and complete mole, this did
not reach statistical significance (P = 0.15). Hydatidiform moles exhi
bited 2+ to 3+ staining intensity, whereas hydropic placentas exhibite
d weaker intensity (1-2+). The finding of p53 gene product overaccumul
ation in partial and complete moles suggests that p53 gene mutations o
r alternatively, post-transcriptional changes in the p53 gene product
occur resulting in inactivation and stabilization of the protein. This
may play a role in uncontrolled trophoblastic proliferation and neopl
astic transformation.