By using an enzyme-bridge immunoperoxidase (PAP) technique, localization of so-called pregnancy-specific beta 1-glycoprotein (SP1) and placental-specific tissue proteins (PP5, PP10, PP11, PP12) was investigated in 19 cases of breast cancer, 24 cases of testicular malignant tumours, 12 cases of gastric cancer and some cases of other malignant tumours. These five glycoproteins isolated from human term placentae and characterized by Bohn are localised mainly in the cytoplasm, or nucleus of syncytiotrophoblast and appear to be specific for the trophoblast. But to a certain percentage these proteins could also be detected in the cytoplasma of malignant cells: In breast cancer, SP1 was present in 52.6% of cases, PP5 in 63.2%, PP10 in 68.4%, PP11 in 55.6% and PP12 in 31.6%. In testicular malignant tumours the detection rates of these proteins varied from 20.8 to 75.0% and in gastric cancer from 41.7 to 66.7%. In total 50% of the tumours tested were SP1-positive, 58.3% PP5-positive, 55.6% PP10-positive, 38.0% PP11-positive and 31.9% PP12-positive. In addition, it was found that mononuclear histiocytes showed a strong cytoplasmic staining for PP10 and PP12 and that a few other non-cancerous cells (i.e. striated cells in gastric metaplasia, gastric polyps etc.) stained for PP5, PP10, PP11 and/or PP12. All control sections were negative in malignant cells as well as in other tissue cells. This study confirms the reports that some kinds of malignant tumours produce SP1 and indicates that the ectopic production of proteins normally produced by the trophoblast is a common finding in malignant tumours. It furthermore suggests that such proteins may be useful as markers in monitoring patients with malignant diseases. The possible mechanisms of ectopic production of these inappropriate proteins in malignant tumours are discussed.

With use of an enzyme-bridge immunoperoxidase (PAP) technique, an immunohistochemical localization of the two new placenta-"specific" tissue proteins, PP5 and PP11, was investigated in 16 cases of breast cancer. PP5 was localized in the cytoplasm of breast cancer cells in 62.5% of cases examined and PP11, in 46.7%. Thus PP5 and PP11 may be markers for breast cancer and the detection of these proteins in sera from breast cancer patients may be more reliable and useful in the detection and monitoring of breast cancer patients than the determination of SP1, PP10, or PP12, other pregnancy "specific" proteins.

By using an immunoglobulin enzyme bridge (PAP) technique, the location of two ubiquitous tissue proteins (PP8, PP9) and three placental specific tissue proteins (PP10, PP11, PP12) was investigated in ethanol/acetic acid-fixed paraffin-embedded human term placentae. PP8 was found mainly in both the cytoplasm and the nucleus of trophoblast cells (chorion) and syncytiotrophoblast (villi). PP9 was found in the cytoplasm of trophoblast cells (chorion), the fibrous part of interstitial connective tissues (villi), and the cytoplasm of histiocytes (villi, amnion, and decidua). PP10 was found in the cytoplasm of epithelium (amnion) and in both the cytoplasm and the nucleus of syncytiotrophoblast (villi). PP12 was found in the cytoplasm of histiocytes in decidua, amnion, and chorion and the cytoplasm of syncytiotrophoblast (villi). In addition, stains for PP8, PP10, and PP12 were taken up by the cytoplasm of histiocytes found in amnion, villi, the intervillous space, and decidua, in contrast to PP11, which was found to be specific to the cytoplasm of trophoblast cells (chorion and villi). Possible clinical applications of these findings are discussed.

The occurrence and location of proteins antigenically related to human pregnancy specific beta 1-glycoprotein (SP1) and to human placental tissue proteins (PP5, PP8, PP9, PP10, PP11, PP12) were studied in the afterbirth (placenta, membranes, decidua, and umbilical cord) of cynomolgus monkeys with use of an immunoglobulin enzyme bridge (PAP) technique. The results were basically the same throughout pregnancy. The syncytiotrophoblast of villi showed clear positive stainings for SP1, PP8, PP9, and PP11, whereas the cytotrophoblast (villi) was found to show clear positive staining for PP9 only. The main sources of proteins related to SP1, PP9, and PP11 were the syncytiotrophoblast cells of the villi and PP8, the syncytiotrophoblast cells of villi as well as the chorionic trophoblast cells. PP12 was mainly located in histiocytes found in the decidua, umbilical cord, amnion, and chorion. There were only traces of PP5 and PP10 in the placentae of cynomolgus monkeys throughout gestation. As in human placentae some granulocyte-like blood cells in the intervillous space were strongly positive for PP8, PP10, and PP12. The findings in the afterbirth of cynomolgus monkeys were similar to those in the human; the monkey could thus serve as a model for the investigation of the new placental proteins.

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