Characterization of human leukocyte antigen-G (HLA-G) expression in endometrial adenocarcinoma.
ABSTRACT 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.
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.
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.
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.
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ABSTRACT: The HLA-G gene displays several peculiarities that are distinct from those of classical HLA class I genes. The unique structure of the HLA-G molecule permits a restricted peptide presentation and allows the modulation of the cells of the immune system. Although polymorphic sites may potentially influence all biological functions of HLA-G, those present at the promoter and 3' untranslated regions have been particularly studied in experimental and pathological conditions. The relatively low polymorphism observed in the MHC-G coding region both in humans and apes may represent a strong selective pressure for invariance, whereas, in regulatory regions several lines of evidence support the role of balancing selection. Since HLA-G has immunomodulatory properties, the understanding of gene regulation and the role of polymorphic sites on gene function may permit an individualized approach for the future use of HLA-G for therapeutic purposes.Cellular and Molecular Life Sciences CMLS 02/2011; 68(3):369-95. · 5.62 Impact Factor
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ABSTRACT: In a previous study, we demonstrated that human leucocyte antigen G (HLA-G) was aberrantly expressed in a majority of primary colorectal carcinomas, and that the detection of HLA-G expression had a strong and independent prognostic value in human colorectal cancer. In the current study, we look into whether the aberrant expression of HLA-G is also related to non-small cell lung cancer (NSCLC). The expression of HLA-G was investigated immunohistochemically in 106 patients with NSCLC. The correlation between HLA-G status and various clinicopathological parameters was analysed. As well, the level of HLA-G expression was also compared to the survival rate of patients with NSCLC. In total, we found that in 75% (79/106) of the primary site of NSCLC, an aberrant HLA-G expression was detected. However, this expression was not observed in the normal lung tissues. HLA-G expression in NSCLC was significantly correlated with lymph nodal metastasis, clinical stages of the disease, and host immune response (P = 0.0001, 0.0001, and 0.027, respectively). Patients with HLA-G positive tumours had a significantly shorter survival time than those with tumours that were HLA-G negative (P = 0.001). In addition, through multivariate analysis, HLA-G exhibited an independent prognostic factor (P = 0.01, relative risk 4.09; 95% confidence interval 1.40-11.9). All in all, our results indicate that the expression of HLA-G is a characteristic feature of NSCLC, and they suggest that immunostaining by anti-HLA-G antibodies may be a potentially useful prognostic indicator.Lung Cancer 12/2007; 58(2):267-74. · 3.39 Impact Factor
- Cancer Letters - CANCER LETT. 01/2010; 1.