Expression of Placental Alkaline Phosphatase Isoenzyme in Human Gastrointestinal Carcinomas as Identified Using Monoclonal Antibodies

Mouse monoclonal antibodies (MAbs) against MKN1 human gastric adenosquamous carcinoma cells were produced, and selected to bind to the placental alkaline phosphatase (PLAP) expressed by the cancer cells. One of the MAbs, M1H2, was highly specific for PLAP or PLAP-like isoenzyme and did not cross-react with intestinal or liver alkaline phosphatase enzymes. Another MAb, M1H9, also became bound to PLAP or a PLAP-like isoenzyme with a lower binding activity than M1H2, but also reacted weakly with enzymes other than PLAP or PLAP-like enzymes, indicating that the binding of M1H9 to PLAP or a PLAP-like enzyme was nonspecific. The antigen molecule recognized by MAbs was a Mr 65,000 peptide, being equivalent to a PLAP monomer as estimated by Western blot analysis. Immunocytochemical examination showed that these MAbs detected PLAP or a PLAP-like enzyme over the surface of MKN1, SCH, and A431 cells which express the enzyme with a uniform distribution, whereas reactivities to non-PLAP-producing, MKN45 and KATO-III cells were not detected. Immunohistological studies of human gastrointestinal carcinomas using M1H2 demonstrated that 26 of 29 esophageal carcinomas (90%), 12 of 27 gastric carcinomas (44%), and 10 of 18 colorectal carcinomas (56%) were reactive with the MAb. Noncancerous tissues adjacent to cancers did not react with the MAb. These results indicate that PLAP or the PLAP-like enzyme in gastrointestinal cancers may be regarded as cancer-specific antigens, and that M1H2 may be of value as a marker in gastrointestinal cancers, especially esophageal cancers