(Glypican 3)

Nature: GLP3 is a membrane proteoglycan, 60-70 kDa (core protein only), encoded by a gene on Chr Xq26, one of six members of the GLP family, which together with the syndecan family represent the major groups of cell surface heparin sulphate proteoglycans. Function and occurrence: GLPs play a vital role in developmental morphogenesis by modifying cell signaling pathways thus contributing to cellular proliferation and tissue growth. GLPs are regulators for the Wnt and Hedgehog cell signaling pathways, and for fibroblast growth factor and bone morphogenic protein signaling. GLPs are oncofetal proteins, i.e., they are expressed in embryonic structures (such as liver and intestine), but undetectable in the corresponding normal adult structures but re-expressed in malignant tumors developed from these structures. In normal adult tissues only placental syncytiotrophoblast and villus core mesenchymal cells are GLP3 positive.


+: >90% positive, +/-: 50-90% positive, -/+: 10 - >50% positive, -(+): 1-<10% positive, -: <1% positive, ?: conflicting evidence or insufficient information.
+ GLP3 is detected in almost all cases of choriocarcinoma, yolk sac tumour, hepatoblastoma, and atypical teratoid/rhabdoid tumor.
+/- GLP3 is detected in most cases of hepatocellular carcinoma (HCC) (70-90%), especially in low differentiated tumors, where it is a negative prognostic factor. Acinar pancreatic carcinoma and Merkel cell carcinoma also express GLP3 in most cases.
-/+ GLP3 is less frequently detected in dysplastic liver cell nodule (where focal positivity may indicate HCC development), squamous cell carcinoma (esophagus, anus), gastroentestinal adenocarcinomas, ovarian carcinomas, especially clear cell carcinoma (30%), in embryonal carcinoma (15%, often focal), Wilms’ tumor (40%), and alveolar and embryonal rhabomyosarcoma (30%).
- GLP3 is not detected in liver focal nodular hyperplasia or liver cell adenoma (focal positivity may indicate HCC development), ovarian sex cord stromal tumor, seminoma/dysgerminoma, and also not in carcinomas and sarcomas apart from the above mentioned.


GLP3 is an important marker for the identification of HCC (+/-) vs. liver cell adenoma (-), focal nodular hyperplasia (-), cholangiocellular carcinoma (-) and metastatic carcinoma of the liver (-). GLP3 is also relevant as a sensitive (though not specific) marker for yolk sac tumour (+) vs. clear cell carcinoma (-/+) and embryonal carcinoma (-/+).


Placenta is recommended as positive tissue control for GLP3. Virtually all syncytiotrophoblasts and cytotrophoblasts must show a moderate to strong predominantly cytoplasmic but also membranous staining reaction. Dispersed villous stromal cells must show an at least weak cytoplasmic staining reaction. Appendix can be used as negative tissue control. The vast majority of epithelial cells must be negative. Dispersed basal epithelial cells can show a weak cytoplasmic staining reaction.

Selected references

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09.12.14 - SN/MV/LE