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Placental protein 4 (PP4) is a soluble placental tissue protein which was isolated from human placenta. The aim of the present study was to demonstrate the localization of cells containing PP4 in human placenta and in various female genital tissues under normal conditions. PP4 immunoreactive structures were demonstrated by using the peroxidase-antiperoxidase immunohistochemical technique. The samples were obtained from normal human placenta, umbilical cord, uterine cervix, endometrium, ovary and vulva. The most differentiated trophoblastic cells, the syncytiotrophoblasts, as well as the intermediate trophoblast cells contained PP4. PP4 immunoreactivity was present in umbilical cord as well. Occasionally PP4 was detected in normal ovarian, endometrial or vulvar tissue samples. Cervix and myometrium were free of PP4 immunoreactive material. PP4 staining was cytoplasmic. Our findings indicate that PP4 cannot be considered specific for the placenta since it is present in some human adult tissues as well.

The aim of the study was to demonstrate the localization of placental protein 4 (PP4) in different nontumorous and tumorous tissues originating from the female genital tract. PP4 immunoreactivity was demonstrated using the peroxidase-antiperoxidase immunohistochemical technique. Tissue samples were obtained from the cervix and body of the uterus, ovary, vulva and from gestational trophoblastic tumors. PP4-positive cells were present in nontumorous tissues with various pathologic findings, and in many but not all benign gynecological tumors. Similar numbers of PP4-positive cells were located in malignant and benign gynecological tumors; however, PP4 staining intensity was greater in the malignant lesions. PP4-positive cells were found in hydatidiform moles and in choriocarcinoma. PP4 was distributed mainly in the cytoplasm, but it was also bound to the cell membrane. We conclude from these studies that PP4 is located in a variety of benign and malignant cells of the female genital tract and that these cells may be the source of plasma PP4 found in patients with these conditions.

6 patients with invasive mole and 5 patients with choriocarcinoma were treated from 1983 till 1986. Serum samples were analyzed by simultaneous determining of pregnancy-specific beta-1-glycoprotein (SP-1) using enzyme-linked immunosorbent assay (ELISA) and beta subunit of human chorionic gonadotropin (beta-hCG) using Serono radioimmunoassay kit. In 2 patients with metastatic gestational trophoblastic disease (MGTD) SP-1 peaks were found during chemotherapy. In patients with MGTD with normalized beta-hCG levels a repeated, temporary elevation of isolated SP-1 levels was observed within some months following chemotherapy. After the last isolated peak of SP-1 the pulmonary metastases disappeared. This phenomenon was interpreted as a consequence of the oncolytic process in the affected tissue. In 1 patient with nonmetastatic choriocarcinoma SP-1 ELISA pseudoreaction was found. To recognize these pseudoreactions, a control plate with nonimmunized rabbit IgG was used, simultaneously with SP-1 determinations.

A comparative analysis of radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) techniques in determining placental protein 14 (PP14) levels in gynecologic patients was performed. Serum PP14 levels were assessed in the patients in the last period of gestation, during menopause and in healthy nonpregnant controls. The possible discrepancy in PP14 levels was also examined in gynecologic patients with benign and malignant tumors. Both RIA and ELISA techniques proved to be sufficiently sensitive to measure PP14 concentration.

Placental protein 4 (PP-4), a recently characterized glycoprotein from human placenta, was studied using a specific double-antibody radioimmunoassay in sera of 130 volunteers, 76 ovarian tumor patients and in ovarian tumor cyst fluid and ascites of 21 patients. Elevated levels (greater than 3 micrograms/l) were found in 45 of 52 ovarian cancer patients (86.5%). PP-4 levels correlated significantly with staging. 31 patients with malignant ovarian tumor were monitored on 2-9 occasions during 5-82 weeks. Rising or falling levels of PP-4 correlated with progression or regression of disease in 25 of 31 instances (80.6%). Elevated levels were found in 10 of 24 benign and borderline ovarian tumors. Elevated PP-4 level does not indicate malignancy in each case. PP-4 can be regarded as tumor-associated antigen and an tumor marker in oncological practice.

The present study was undertaken to test the parallel detectability of ovarian cancer antigen CA 125 and gastrointestinal cancer antigen CA 19-9 in the sera of patients with malignant ovarian tumors, benign ovarian tumors, endometrial cancers, cervical cancers, colorectal cancers, and trophoblastic tumors and in early 1st-trimester pregnant as well as in healthy nonpregnant controls. In all kinds of gynecologic and colorectal tumors raised concentrations of both antigens were found with the exception of malignant nonepithelial ovarian tumors where neither of the antigens showed positive reaction. The most positive cases were found in the group with epithelial ovarian cancers. Of the two antigens CA 125 was the more responsive. No positive cases were found with either of the antigens in non-pregnant healthy controls or in patients with benign ovarian tumors. The parallel determination of the two antigens gives us a better opportunity to recognize pelvic tumors and further may enable us to distinguish ovarian and colorectal tumors.

455 serial serum samples from 41 patients with trophoblastic tumour were analysed. Pregnancy-specific beta-1 glycoprotein (SP1), human chorionic gonadotropin (hCG), and placental protein 5 (PP5) were measured by specific radioimmunoassay. Pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG) was measured by electroimmunoassay. SP1 and hCG levels were high in 36 and 35 patients respectively; alpha 2-PAG concentration was also high in 29 patients. PP5 was found only in patients with a hydatidiform mole and it disappeared from serum within a few hours of evacuation. SP1 and hCG levels decreased during the course of the treatment but seronegativity was reached only after some months: hCG was still detectable after that and disappeared from the serum more slowly. Both parameters were sensitive indicators of residual tumour activity and indicated the need more effective treatment some months before clinical manifestations of recurrence became evident. In some patients only one of the tumour markers was present during follow-up, indicating the importance of careful monitoring including the measurement of serum SP1 and hCG levels. A positive correlation between alpha 2-PAG and hCG, SP1 and the clinical course was found only in 80% of patients a finding which demonstrates the limited value of alpha 2-PAG measurements.