Immunohistochemistry for the imprinted gene product IPL/PHLDA2 for facilitating the differential diagnosis of complete hydatidiform mole

OBJECTIVE: To determine if immunohistochemistry for PHLDA2 (also known as IPL and TSSC3), the product of a paternally imprinted, maternally expressed gene, can be used as a tool in the differential diagnosis of molar gestations. STUDY DESIGN: Twenty-five cases (15 complete moles, 5 partial moles and five hydropic abortions) were stained by immunohistochemistry for PHLDA2 and scored (without knowledge of the diagnosis) for positivity in the villous cytotrophoblast and then compared to adjacent sections stained by p57 ^KIP2 immunohistochemistry. RESULTS: All partial moles and hydropic abortions were positive for PHLDA2 and p57 ^KIP2. There was strong PHLDA2 staining of the cytoplasm in virtually all cells of the villous cytotrophoblast, while p57 ^KIP2 was localized to the nucleus in a subset of those cells. All complete moles were negative for both markers in the villous cytotrophoblast. CONCLUSION: Immunohistochemistry for PHLDA2 serves as a practical and reliable diagnostic marker for the discrimination of complete mole from partial mole and hydropic abortion. Since the immunohistochemical diagnosis of complete mole is based on a negative result, absence of staining, the use of both markers (PHLDA2 and p57 ^KIP2) together could increase the level of confidence when making this prognostically important distinction.