Alkaline phosphatases are a heterogeneous group of glycoproteins confined to the cell membranes. There are three tissue-specific alkaline phosphatases; PLAP, germ cell AP (GCAP) and intestinal AP (IAP), which are 90-98% homologous with a molecular weight of 57-70 kDa. Their genes are clustered on chromosome 2q. There is also a tissue non-specific AP (TNAP), sometimes called PLAP-like enzyme, which has less homology with the tissue specific types. TNAP is encoded by a gene on chromosome 1p. PLAP is a dimer of 65 kDa consisting of 530 amino acids and is thought to play a role in guiding migratory cells and transport specific molecules over the plasma membrane. PLAP is expressed in placenta from the 8th week of gestation and the concentration increases continually throughout the pregnancy. PLAP can be separated into three distinct isoenzymes corresponding to early, mid and term placenta. PLAP is also expressed in the endocervix and the Fallopian tubes. The other alkaline phosphatases, GCAP and IAP are more widely distributed and are seen, for instance, in migrating germ cells, thymus and foetal intestinal epithelium. TNAP which is less homologous with PLAP, is widely expressed in foetal tissue.
Since different antibodies may recognize PLAP alone, or PLAP together with the other AP’s and TNAP, the reaction pattern may be varying. However, in general, PLAP can be recognized consistently in seminoma/dysgerminoma/germinoma (with the exception of spermatocytic seminoma) and intratubular germ cell neoplasia (carcinoma in situ testis) as well as in most cases of embryonal carcinoma and some cases of yolk sac tumour. Hydatiform mole and choriocarcinoma are also PLAP positive. Furthermore, particularly with clone 8A9, PLAP has been reported to be expressed in myogenic tumours, desmoplastic small round cell tumour and also occasional other tumours, such as pulmonary adenocarcinomas, serous and endometrioid carcinoma and gastric and colorectal adenocarcinomas. It should be noted, however, that some of this information is older than 10 years and the antibodies used may have been less specific.
PLAP is an important marker in the identification of germ cell tumours and intratubular germ cell neoplasia. However, OCT3/4 appears to show a higher signal/noise ratio. Also PLAP has been used in the differential diagnosis of uncharacteristic tumours in, e.g., mediastinum. PLAP may also be used in the panel for the recognition of unusual neoplasms such as desmoplastic small round cell tumour, rhabdomyosarcoma and choriocarcinoma.
Placenta is the best choice regarding positive control, in which the cytotrophoblasts and syncytiotrophoblasts must show an as strong as possible predominantly membranous but also cytoplasmic staining reaction, while no staining should be seen in the stromal cells. Appendix may be used as negative control, in which no structures/cells should show any staining reaction
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