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

Brooke Army Medical Center, Houston, Texas, United States
Gynecologic Oncology (Impact Factor: 3.77). 11/2006; 103(1):25-30. DOI: 10.1016/j.ygyno.2006.01.045
Source: PubMed


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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    • "These suggested that HLA-G might play an important role in the tumorigenesis of NPC. Supportively, the overexpression of HLA-G antigens has been detected in various types of human malignancies, including gastric carcinoma 18, lymphoma 19-20, ovarian 21 and endometrial carcinoma 22. "
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    ABSTRACT: Human leukocyte antigen G (HLA-G) has multiple immune regulatory functions including the induction of immune tolerance in malignancies. The roles of HLA-G have not been investigated in nasopharyngeal carcinoma (NPC). This study is aimed to evaluate the role of HLA-G as prognostic factor for NPC patients as well as its role in the immune regulation. Western assays showed high HLA-G expression in NPC cell lines, but low in the immortalized nasopharyngeal epithelial cell line NP69. HLA-G protein was further detected in 79.2% of 552 NPC specimens with immunohistochemistry (IHC), but not in normal nasopharyngeal epithelium tissue. Moreover, high expression of HLA-G predicted poor survival of NPC patients and positively correlated with tumor N classification and recurrence or metastasis. Multivariate analysis indicated that HLA-G was an independent and unfavorable prognostic factor. Furthermore, the presence of CD68+ macrophages and IL-10 were also examined, which are two prognostic markers of NPC and important factors for regulating immune surveillance. The correlations of HLA-G with these two immune factors were revealed in NPC tissues. Taken together, our results suggest that HLA-G is an independent biomarker for NPC prognosis, and HLA-G might contribute to NPC progression, which might jointly regulate immune surveillance in NPC together with macrophages and IL-10.
    International journal of biological sciences 06/2012; 8(6):891-900. DOI:10.7150/ijbs.4383 · 4.51 Impact Factor
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    • "A recent study stratified tumors according to the magnitude of HLA-G expression, i.e., lesions exhibiting no expression, less than 30% expression , and more than 30% expression (Carosella et al. 2008). Among some tumors affecting women, ovarian carcinoma expressed HLA-G in 61% of specimens (45/74) (Sheu and Shih 2007), endometrial adenocarcinoma in 55% (24/44) (Barrier et al. 2006), and breast cancer in 39% (14/36) (Lefebvre et al. 2002). "
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    ABSTRACT: Human leukocyte antigen-G (HLA-G) is a non-classical major histocompatibility complex class Ib molecule that acts as a specific immunosuppressor. Some studies have demonstrated that human papillomavirus (HPV) seems to be involved in lower or absent HLA-G expression, particularly in cervical cancer. In this study, we performed a cross-sectional study, systematically comparing the qualitative expression of the HLA-G5 isoform in invasive cervical carcinoma (ICC), stratifying patients according to the presence [ICC with metastasis (ICC(W))] and absence [ICC without metastasis (ICC(WT))] of metastasis, correlating these findings with interference of HPV and demographic and clinical variables. Seventy-nine patients with a diagnosis of ICC were stratified into two groups: ICC(WT) (n=52 patients) and ICC(W) (n=27). Two biopsies were collected from each patient (one from the tumor lesion and one from a lymph node). Immunohistochemistry analyses were performed for the HLA-G5 isoform, for HPV detection, and virus typing. HLA-G5 isoform molecules were detected in 25 cases (31.6%), 17 (32.7%) without metastasis and 8 (29.6%) with metastasis. HPV was detected in the cervical lesions of 74 patients (93.7%), but low expression of the HLA-G5 isoform was observed in all HPV-related cases. These findings are important; however, additional studies are necessary to identify the influence of HPV with HLA-G5 isoform expression on invasive cervical malignancies.
    Journal of Histochemistry and Cytochemistry 09/2009; 58(5):405-11. DOI:10.1369/jhc.2009.954131 · 1.96 Impact Factor
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    ABSTRACT: AIM:: To investigate classical MHC class I and non-classical MHC (HLA-G) expression in a large cohort of endometrial cancer patients to determine the prognostic value of these cell surface markers and their relation with clinicopathological variables. METHODS:: Tissue microarrays containing epithelial endometrial carcinoma tissue from 554 patients were stained for classical and non-classical MHC class I using the following monoclonal antibodies; 4H84 (anti-HLA-G), beta2-m (anti-beta2-m) and HC-10 (MHC class I antigen heavy chain). Expression data was linked to known clinicopathological characteristics and survival. RESULTS:: HLA-G up-regulation and MHC class I down-regulation in neoplastic cells was observed in 40% and 48%, respectively. Non-endometrioid tumor type, advanced stage disease (FIGO stage >/=II) and poorly or undifferentiated tumors were associated with MHC class I down-regulation. Absence of HLA-G expression was independently associated with MHC class I down-regulation. In univariate analysis, MHC class I down-regulation was a predictor of worse disease specific survival. CONCLUSION:: Prognostic unfavorable tumor characteristics are correlated with down-regulation of MHC class I expression in endometrial cancer cells. Furthermore, down-regulated MHC class I has a negative impact on disease specific survival, observed in a large cohort of endometrial cancer patients. As there seems to be a relation between classical and non-classical MHC class I molecules (HLA-G), further research is warranted to unravel this regulatory mechanism. (c) 2009 UICC
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