Characterization of human leukocyte antigen-G (HLA-G) expression in endometrial adenocarcinoma

Objectives.: The current study sought to determine if endometrial adenocarcinomas express human leukocyte antigen-G (HLA-G), an immune-regulatory protein, and if degree of expression correlates with the stage of carcinoma. Methods.: Forty-four primary endometrial adenocarcinomas were tested using immunohistochemical staining with the 4H84 anti-HLA-G monoclonal antibody. Metastatic implants were not included. A subset of 10 samples was tested using RNA in situ hybridization to confirm the presence of HLA-G transcript. Results of staining were analyzed with respect to grade, tumor histology, and stage of disease. Spearman rank correlation was used to assess tumor grade, histology, and disease stage as a function of HLA-G protein staining. Receiver-operator characteristic (ROC) curve analysis was used to determine the feasibility of HLA-G protein staining as a clinical marker for advanced stage disease. Results.: Immunohistochemical staining for HLA-G protein was seen in 55% (24/44) of primary site endometrial adenocarcinomas and localized to glandular but not stromal epithelium. RNA in situ hybridization confirmed the presence of transcript in the majority of samples tested and also localized to glandular epithelium. A significant correlation was seen with increasing HLA-G protein staining and increasing stage of endometrial cancer, P < 0.01. HLA-G was found to be a fair discriminator as a test for metastatic disease with an area under the ROC curve of 0.75 for metastatic versus non-metastatic disease. Conclusions.: HLA-G protein is expressed in a significant number of endometrial adenocarcinomas, in which it is localized to the glandular epithelium. HLA-G may serve as a clinical marker for the preoperative prediction of metastatic endometrial cancer.