p57^kip2 is useful in the classification and differential diagnosis of complete and partial hydatidiform moles

Aims: To determine the utility of p57^kip2 in the diagnosis of hydatidiform mole. p57^kip2 protein is a cyclin-dependent kinase inhibitor (CDKI) and is strongly paternally imprinted, being expressed from the maternal allele. It has been hypothesized that complete mole (CHM) with only the paternal genome would display reduced or nearly absent expression of p57^kip2 compared to partial mole (PHM) having both paternal and maternal genomes. Methods and results: The immunohistochemical expression of p57^kip2 protein was investigated using paraffin-embedded tissue sections in histologically unequivocal cases of CHM (n = 51), PHM (n = 7), invasive mole (n = 1), and hydropic miscarriage (n = 2), as well as in histologically undetermined cases (n = 9). In the histologically unequivocal complete and invasive moles, expression of p57^kip2 was absent except for one case in which villous cytotrophoblast covering the villous stroma was positive (51/52) as well as villous stromal cells (51/52). In contrast, it was strongly and continuously expressed in both villous cytotrophoblast and stromal cells in all cases of PHM and hydropic miscarriage. Among the nine histologically undetermined cases, five cases showing p57^kip2 immunopositivity and hyperploid DNA were classified as PHMs, two cases showing p57^kip2 immunonegativity and hyperploidy as CHMs, and two cases with p57^kip2 immunopositivity and diploid DNA as hydropic miscarriage and diploid PHM, respectively, upon review of the histopathological findings. Intermediate trophoblast forming trophoblastic columns or anchoring villi and extra-villous trophoblast at the implantation site showed variable expression of p57^kip2 in all gestational conditions. Maternal decidua showed diffuse and strong p57^kip2 expression, whereas syncytiotrophoblast was completely negative in all cases regardless of the diagnosis. Conclusions: In summary, p57^kip2 immunostaining results correlated well with morphological features of molar pregnancies and were helpful in determining histologically equivocal cases.