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

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	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

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