HLA-G is a nonclassical MHC class I antigen that interacts with natural killer cells and binds CD8. It is important for the escape from immunosurveillance and is thought to play a role in immunotolerance of the placenta.

Immunohistochemical expression

As of September 2006, the antibody 4H84 that is reactive on paraffin sections was not yet available commercially5.

Expression is seen in intermediate trophoblast but is highly restricted in all other tissues. The normal implantation site intermediate trophoblast shows strong membranous and cytoplasmic positivity in 100% of cells. The normal intermediate cells of the chorion laeve show staining of 60-70% of cells, restricted to those with eosinophilic cytoplasm, while clear cells are negative. All trophoblastic lesions showed immunoreactivity of at least 70% of cells. Endometrium, myometrium and endothelial cells are negative1.


Exaggerated placental site



Placental site nodule


Epithelioid trophoblastic tumour


Placental site trophoblastic tumour




invasive cervical squamous cell carcinoma


poorly differentiated endometrial carcinoma


low grade stromal sarcoma


malignant mixed mesodermal tumour







In placental site trophoblastic tumour, the lesion cells are confluent, whereas in exaggerated placental site the cells infiltrate the endomyometrium in cords; this distinction can be highlighted using HLA-G1.

Melanoma3, renal cell carcinoma2 and large cell carcinoma of lung4 may show scattered immunoreactive cells.

Diagnostic utility

Identification of gestational trophoblastic tumours and tumour-like lesions, derived from intermediate trophoblast1. In its consistent staining of lesions derived from intermediate trophoblast, it appears to be superior to hCG, hPL, Mel-Cam, PlAP, cytokeratin 18 and inhibin-a. A panel of the latter is useful in differentiating between these enities.


1 Singer, G., R. J. Kurman, et al. (2002). "HLA-G immunoreactivity is specific for intermediate trophoblast in gestational trophoblastic disease and can serve as a useful marker in differential diagnosis." Am J Surg Pathol 26(7): 914-20.

2 Ibrahim, E. C., N. Guerra, et al. (2001). "Tumor-specific up-regulation of the nonclassical class I HLA-G antigen expression in renal carcinoma." Cancer Res 61(18): 6838-45.

3 Paul, P., N. Rouas-Freiss, et al. (1998). "HLA-G expression in melanoma: a way for tumor cells to escape from immunosurveillance." Proc Natl Acad Sci U S A 95(8): 4510-5.

4 Urosevic, M., M. O. Kurrer, et al. (2001). "Human leukocyte antigen G up-regulation in lung cancer associates with high-grade histology, human leukocyte antigen class I loss and interleukin-10 production." Am J Pathol 159(3): 817-24.

5 Mao TL, Seidman JD, Kurman RJ, et al. Cyclin E and p16 Immunoreactivity in Epithelioid Trophoblastic Tumor-An Aid in Differential Diagnosis. Am J Surg Pathol 2006; 30:1105-1110


This page last revised 23.9.2006.

©SMUHT/PW Bishop