Circulating levels and tissue localization of placental protein five (PP5) in pregnancy and tropho‐blastic disease: Absence of PP5 expression in the malignant trophoblast

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Abstract
Placental protein five (PP5) was studied by radio‐immunoassay in 360 serum samples from 334 pregnant women, 96 serum samples from eight patients with trophoblastic disease, and 80 samples from apparently healthy women. PP5 was not found in the serum of healthy controls. It became detectable in maternal serum 8 weeks after the last menstrual period, and the levels progressively increased as pregnancy advanced. The highest levels (mean 26–29 ng/ml) were seen between weeks 37–39 of gestation. PP5 was rarely found in the serum of patients with trophoblastic disease. The first pretreatment samples of two patients with hydatidiform mole had PP5 levels of 0.6 and 2 ng/ml when the concentrations of human chorionic gonadotrophin (hCG) and pregnancy‐specific beta‐1‐glycoprotein (PSBG) were high, whereas the subsequent 17 samples were PP5‐negative. All seven samples from a patient with invasive mole and 70 samples from five patients with choriocarcinoma were PP5‐negative including those with high hCG and PSBG concentrations. Even a patient whose choriocarcinoma followed term pregnancy had no detectable PP5 in the serum. The occurrence of PP5 in tissue was studied by the three‐layer bridge immunoperoxidase method. PP5 was localized in the syncytiotrophoblast between 6 and 42 weeks of gestation, but the cytotrophoblast was PP5‐negative. The staining for PP5 was positive in all hydatidiform moles tested and in one of 10 cases of invasive mole. Choriocarcinomas were constantly PP5‐negative (6 cases). In the light of the biological role of PP5 as trypsin and plasmin inactivator its presence in normal and absence from malignant trophoblast suggests that PP5 may be involved in the regulation of trophoblastic invasiveness. The absence of PP5 expression in malignant trophoblastic disease makes it possible to use the serum PP5 measurement for the differential diagnosis of trophoblastic disease and normal pregnancy: in normal pregnancy the placental proteins PP5, hCG and PSBG are all present in serum 10 weeks after the last menstrual period, whereas in malignant trophoblastic disease hCG and PSBG are expressed in the absence of PP5.