HLA-G

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

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	9/91
	Placental site nodule	16/16 (70-90% of cells, particularly those cells with eosinophilic cytoplasm. Cells with clear cytoplasm are almost always negative.)1
	Epithelioid trophoblastic tumour	13/13 (70-100% of cells, particularly those cells with eosinophilic cytoplasm. Cells with clear cytoplasm are almost always negative.)1
	Placental site trophoblastic tumour	14/14 (100% of cells showed strong membranous and cytoplasmic positivity)1
	Choriocarcinoma	14/14 (positivity restricted to mononuclear cells; syncytial cells are negative.)1
	invasive cervical squamous cell carcinoma	0/101
	poorly differentiated endometrial carcinoma	0/91
	low grade stromal sarcoma	0/91
	malignant mixed mesodermal tumour	0/11
	leiomyoma	0/31
	leiomyosarcoma	0/21

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.

References

¹Singer, 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.

²Ibrahim, 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.

³Paul, 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.

⁴Urosevic, 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.

This page last revised 6.4.2004.

©SMUHT/PW Bishop