p57KIP2 immunostaining in the diagnosis of complete versus partial hydatidiform moles

Sir: Several recent publications, including two major articles published in Histopathology, have reported on the use of immunohistochemical staining for p57 as a useful diagnostic technique to distinguish between complete versus partial hydatidiform moles. p57 is an imprinted gene in the placenta and is therefore only normally expressed from the maternal allele. Therefore, positive nuclear p57 immunostaining is seen in both non-molar miscarriages and partial hydatidiform moles, which contain a maternal genetic contribution. In contrast, androgenetic complete hydatidiform moles do not contain an expressed maternal genomic contribution and therefore do not exhibit the same pattern of p57 immunostaining. We have found the use of p57 immunostaining to aid diagnosis in a proportion of cases, but we have also recently noted a significant number of referrals in which the interpretation of p57 immunostaining has complicated the original diagnosis made by the referring pathologist, the correct diagnosis having being made on the basis of the histomorphological features identified at the referring hospital, with the conclusion erroneously altered on the basis of incorrect interpretation of the p57 staining pattern. We would therefore like to reiterate that p57 immunostaining in this context cannot simply be regarded as either present or absent, the nature and extent of staining requiring assessment. In non-molar biparental products of conception, immunostaining with p57 demonstrates positive nuclear expression within the villous stroma and cytotrophoblast, staining more than 70% of cytotrophoblastic cells, in addition to positive nuclear staining in the components of extravillous trophoblast (Figure 1, top). In contrast, in androgenetic complete hydatidiform moles, there is either a complete absence of nuclear staining within the villous stroma and cytotrophoblast, or only scattered positive staining cells are seen. However, even in complete hydatidiform moles, the extravillous trophoblast strongly expresses p57 (Figure 1, bottom), and indeed, gestational trophoblastic tumours which are derived from p57 non-expressing complete hydatidiform moles usually express p57 in the subsequent tumour. Thus far, there is no satisfactory biological explanation for the selective immunoreactivity of the extravillous trophoblast for p57 in complete hydatidiform moles. Rodent studies have demonstrated that it is probably required for the normal development and differentiation of trophoblast subtypes, although possible mechanisms controlling its regional expression remain entirely uncertain. We have now noticed numerous cases which have been referred to the Regional Centre for assessment, in which the initial morphological diagnosis correctly indicated a complete hydatidiform mole, but the presence of strong extravillous trophoFigure 1. Top: photomicrograph of non-molar products of conception demonstrating strong nuclear expression of p57 in the majority of villous cytotrophoblastic cells, in addition to staining of stromal cells and extravillous trophoblast. Bottom: photomicrograph of an androgenetic complete hydatidiform mole demonstrating ‘negative’ p57 in the majority of villous cytotrophoblastic cells. However, occasional cytotrophoblastic and ⁄ or stromal cells may stain and there is strong nuclear staining of extravillous trophoblast even in complete moles. Correspondence 873