Hyponatremia, Antidiuretic Hormone Secretion and Oat Cell Carcinoma of the Lung

Abstract

A carcinoplacental isoenzyme antigen is defined as a catalytically active protein present in a tumor, whose antigenic sites are identical to that of a protein present in the placenta but not in any fetal tissue. A family of placental isoenzymes of alkaline phosphatase (the Regan isoenzyme, the Nagao isoenzyme and Regan variant isoenzyme) is presented as examples of such antigens.Tumor alkaline phosphatases in humans have accordingly been classified as Regan or as non-Regan in type.Experimental evidence is described indicating that normal phenotypes of placental alkaline phosphatase appear in Regan-positive cancer sera. The D-variant phenotype which is considered rare in its occurrence in human placenta was frequently observed in Regan-positive cancer sera. In both pregnancy and cancer sera, D-variant phenotype correlated with marked enzyme inhibition by l-leucine. This latter characteristic is distinctive for the Nagao isoenzyme.In a case of ovarian cancer exhibiting both Regan and non-Regan isoenzymes, electron micrographs of tumor tissue processed for alkaline phosphatase showed sites of activity in the outer mitochondrial membranes, in the lateral cell borders and microvilli and in the dense-body type lysosomes. An array of mitochondria and endoplasmic reticulum resembling structures seen in placental cells was observed.A review of the literature has centered on polypeptide hormones in cancer, tumor morphology and hormone secretion, aberrant endocrine activity, α-fetoglobulin and carcinoembryonic antigen, enzymes in experimental cancer, tumor alkaline phosphatase and several theoretical considerations.The evidence is consistent with current views that normal genes are active in cancer. From the data and the previous literature, it is suggested that activation of placental and fetal genes may play a role in malignancy and that epigenetic rather than mutational mechanisms apply.