Placental Alkaline Phosphatase (PLAP)

Characteristics

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.

Neoplasms

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.

Application

PLAP is an important marker in the identification of germ cell tumours and intratubular germ cell neoplasia as well as 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.

Visualization

There are several mAbs available with somewhat varying specificity. In Run 14, PL8-F6 and NB10 were shown to give optimal results. Epitope retrieval is important. Clone 8A9 reacts distinctively with both smooth and striated muscle cells, which may cause difficulties with some neoplasms (see above).
Control tissue: Placenta.

Assessments

Run 14 2005

Selected references

Chatzaki E, Gallagher CJ, Iles RK, Ind TE, Nouri AM, Bax CM, Grudzinskas JG. Characterisation of the differential expression of marker antigens by normal and malignant endometrial epithelium. Br J Cancer 1994; 69(6):1010-14.

Dabare AA, Nouri AM, Cannell H, Moss T, Nigam AK, Oliver RT. Profile of placental alkaline phosphatase expression in human malignancies: effects of tumour cell activation on alkaline phosphatase expression. Urol Int 1999; 63(3):168-74.

Goldsmith JD, Pawel B, Goldblum JR, Pasha TL, Roberts S, Nelson Khurana JS, Barr FG, Zhang PJ. Detection and diagnostic utilization of placental alkaline phosphatase in muscular tissue and tumours with myogenic differentiation. Am J Surg Pathol 2002; 26(12):1627-33.

Hamilton-Dutoit SJ, Lou H, Pallesen G. The expression of placental alkaline phosphatase (PLAP) and PLAP-like enzyme in normal and neoplastic human tissues. Immunohistological survey using monoclonal antibodies. APMIS 1990 Sep; 98(9):797-811.

Hattab EM, Tu PH, Wilson JD, Cheng L. OCT4 Immu-nohistochemistry Is Superior to Placental Alkaline Phosphatase (PLAP) in the Diagnosis of Central Nerv-ous System Germinoma. Am J Surg Pathol. 2005 Mar;29(3):368-371.

Millan JL, Fishman WH. Biology of human alkaline phosphatases with special refrence to cancer. Crit Rev Clin Lab Sci, 1995 32:1-39.

Slowikowska-Hilczer J, Walczak-Jedrzejowska R, Kula K. Immunohistochemical diagnosis of preinvasive germ cell cancer of the testis. Folia Histochem Cyto-biol. 2001;39(2):67-72.

Watanabe H, Tokuyama H, Ohta H, Satomura Y, Okai T, Ooi A, Ma Sawubu N. Expression of placental alkaline phosphatase in gastric and colorectal cancers. An immunohistochemical study using the prepared monoclonal antibody. Cancer 1990 Dec; 66(12):2575-82.

Zhang PJ, Goldblum JR, Pawel BR, Fisher C, Pasha TL, Barr FG. Immunophenotype of desmoplastic small round cell tumour as detected in cases with EWS-WT1 gene fusion product. Mod Pathol 2003; 16(3):229-35.