Human placental alkaline phosphatase in benign and malignant ovarian neoplasia.

In benign and malignant ovarian tumor patients, human placental alkaline phosphatase (HPLAP) was determined in serum and extracts from surgical tumor biopsies using a highly specific enzyme-antigen immunoassay based on a mouse monoclonal antibody (E6) to HPLAP. Serum HPLAP levels greater than or equal to 0.1 unit/liter were found in 58% of ovarian cancer patients. Serum carcinoembryonic antigen levels were positive (greater than 5.4 ng/ml) in 17% of these patients. HPLAP was detected in extracts from 13 of the 14 tumors investigated (range, 2.4 to 557 milliunits/g). Only the mixed heterologous Müllerian sarcoma was negative. The highest HPLAP content of normal ovarian tissue was 1.1 milliunits/g. The amount of heat-stable and L-p-bromotetramisole-insensitive alkaline phosphatase was in all cases much higher than the fraction recognized by E6. The neoplastic origin of HPLAP was confirmed immunohistochemically on paraffin sections by an indirect avidin-biotin-peroxidase staining procedure using E6. The staining pattern was compared to the histochemical distribution of total alkaline phosphatase on adjacent sections. A consistency was found between the amount of HPLAP in tissue extracts and its immunohistochemical distribution. In all the tumors, staining for HPLAP was observed mainly on the plasma membranes of carcinoma cells. In 9 of the 10 carcinomas, the histological distribution of HPLAP and also of total alkaline phosphatase was heterogeneous. HPLAP staining, present in one of five normal ovaries, was restricted to germinal inclusion cysts. The present results support the hypothesis that serous ovarian tumors originate from these cysts.

Immunohistochemical localization of placental alkaline phosphatase, carcinoembryonic antigen, and cancer antigen 125 in normal and neoplastic human lung.

Human placental alkaline phosphatase (HPLAP), carcinoembryonic antigen (CEA), and cancer antigen 125 (CA 125) were localized immunohistochemically in paraffin sections of normal lung tissue from 16 patients, using monoclonal antibodies and an indirect avidin-biotin-peroxidase staining procedure. HPLAP and CEA were present in epithelial cells of respiratory bronchioli and alveolar type I pneumocytes. CEA was also observed in the tracheal, bronchial, and bronchiolar epithelium. CA 125 was present in the tracheal, bronchial, bronchiolar, and terminal bronchiolar epithelium; in the tracheal and bronchial glands; and in the pleural mesothelium. Normal and hyperplastic type II pneumocytes were negative for HPLAP, CEA, and CA 125 but were histochemically positive for nonspecific alkaline phosphatase. Fetal lung tissue between 11 and 15 weeks of gestation was negative for HPLAP, CEA, and CA 125. The fetal tracheal and bronchial epithelium, tracheal glands, and pleural mesothelium were positive for CA 125. For ten malignant pulmonary tumors investigated, HPLAP staining was observed in five, CEA in nine, and CA 125 in seven. The localization of HPLAP, CEA, and CA 125 in apparently normal constituents of all pulmonary specimens is in disagreement with the concept that the expression of these substances in the lung is indicative of abnormal cellular activity.

Tumor markers in the human ovary and its neoplasms. A comparative immunohistochemical study.

The incidence and histologic characteristics of the expression of placental alkaline phosphatase (PLAP) in ovarian tumors was compared with that of five other tumor antigens. Three monoclonal antibodies were used for the specific localization of PLAP. PLAP was present in some sex cord cells of the 13-16-week fetal ovary, probably germ cells. In normal ovaries, all antigens except carcinoembryonic antigen (CEA) were frequently found in inclusion cysts; the germinal epithelium was positive only for cancer antigen 125 (CA 125). The frequency and extent of PLAP expression in nonmucinous carcinomas was higher than observed for CA 19-9 and CEA, but was lower than for CA 125 and human milk fat globule antigen. Serous tumors had the highest PLAP expression, followed by endometrioid and poorly differentiated adenocarcinomas, and some other tumors. PLAP was predominantly membranous; its histologic distribution was in general heterogeneous. Different antibodies to PLAP gave different staining intensities in some tumors, but the staining patterns were always qualitatively identical.

Placental alkaline phosphatase and cancer antigen 125 in sera of patients with benign and malignant diseases.

Human placental alkaline phosphatase (hPLAP; EC 3.1.3.1), cancer antigen 125 (CA 125), and carcinoembryonic antigen (CEA) were determined in sera of patients with malignant and nonmalignant disorders. For CA 125 we used two different commercial assay systems, based on the same monoclonal antibody. hPLAP had the same sensitivity (20%) as CA 125 for detecting non-ovarian neoplasia, whereas that of CEA was 45%. For detecting ovarian cancer CA 125 (Cis kit) was slightly more sensitive (50%) than hPLAP (45%), much more than CEA (10%). hPLAP was increased in sera of 2% of patients with nonmalignant disorders, CA 125 in 23%, and CEA in 18%. hPLAP was increased in only one of 10 diabetic patients and two of 50 patients on chronic renal dialysis. CA 125 and CEA were respectively increased in 45% and 23% of all liver pathologies studied and in 12% and 17% of patients with renal insufficiency. The sensitivity of hPLAP for detecting ovarian cancer is slightly inferior to that of CA 125, but its specificity is much higher. We found the Abbott system for CA 125 to be more sensitive than the Cis system.