In 1930 the determination of serum
alkaline phosphatase in patients with bone or
liver disease ushered in the era of clinical enzymology. The association of elevated (bone)
alkaline phosphatase in serum of patients with
osteogenic sarcoma was the first evidence that
tumor cells themselves produced the
enzyme. It became clear, however, in the 1960s that the serum
alkaline phosphatase was not a single
enzyme but consisted of a family of
isozymes originating from liver, bone, intestine, and placenta. This was a consequence of the introduction of a combination of electrophoretic separations, heat inactivation, and organ-specific
amino acid inhibitors. This combination of measurements made possible the demonstration of a serum
alkaline phosphatase of
lung cancer origin, as confirmed by the histochemical visualization in
lung cancer of the Regan
Isozyme (
placental alkaline phosphatase-PLAP). At present, the measurement of PLAP has its greatest utility as a
tumor marker in
seminoma and
ovarian cancer. A PLAP-like
isozyme in normal testis and ovary is expressed in these and other
neoplasias and appears to be related to rare alleles of
placental alkaline phosphatase. Current studies have utilized a panel of
monoclonal antibodies to detect useful
epitopes that suggest that PLAP and PLAP-like
isozymes are coded by different genes. The PLAP gene has now been cloned and sequenced by Millan and others. This fundamental new information is providing a base line that will make it possible to explain the overlapping specificities of intestinal and placental
isozymes, the degree of uniqueness of the PLAP-like
isozyme, the precise mechanism of uncompetitive inhibition by
L-phenylalanine and the evolutionary history of the alkaline
phosphatases.(ABSTRACT TRUNCATED AT 250 WORDS)