The prognostic role of classical and nonclassical MHC class I expression in endometrial cancer

Abstract

The aim of this study was to investigate classical MHC class I and nonclassical MHC (human leukocyte antigen-G [HLA-G]) expression in a large cohort of patients with endometrial cancer, to determine the prognostic value of these cell surface markers and their relation with clinicopathological variables. Tissue microarrays containing epithelial endometrial carcinoma tissue from 554 patients were stained for classical and nonclassical MHC class I using the following monoclonal antibodies: 4H84 (anti-HLA-G), b2-m (anti-beta-2-microglobulin) and HC-10 (MHC class I antigen heavy chain). Expression data were linked to known clinicopathological characteristics and survival. HLA-G upregulation and MHC class I downregulation in neoplastic cells was observed in 40% and 48%, respectively. Nonendometrioid tumor type, advanced stage disease (FIGO stage !II) and poorly or undifferentiated tumors were associated with MHC class I downregulation. Absence of HLA-G expression was independently associated with MHC class I downregulation. In univariate analysis, MHC class I downregulation was a predictor of worse disease-specific survival. Prognostic unfavorable tumor characteristics were correlated with downregulation of MHC class I expression in endometrial cancer cells. Furthermore, downregulated MHC class I has a negative impact on diseasespecific survival, observed in a large cohort of patients with endometrial cancer. As there seems to be a relation between classical and nonclassical MHC class I molecules (HLA-G), further research is warranted to unravel this regulatory mechanism.Endometrial adenocarcinoma is the most common gynecological malignancy in the developed world.1 In The Netherlands, 1,400 women are diagnosed with endometrial cancer each year, of which the majority is an early stage of disease. Prognosis is good in low-stage endometrial cancer (5-year survival International Federation of Gynecology and Obstetrics [FIGO] Stages I and II: 86% and 66%), but it decreases rapidly in higher stages (5-year survival FIGO Stages III and IV: 44% and 16%).2 Nonendometrioid histological type or Grade 3 endometrioid carcinoma (Type II tumors) have been identified as prognostically worse subgroups.3 Classical surgical approaches in combination with radiotherapy and/or chemotherapy have had only limited success in improving the overall survival in Type II endometrial cancer. In future, immunotherapy might fulfill a role in the treatment of endometrial cancer. Additional investigation is warranted to show that the immune system does play a (prognostic) role in this type of cancer. 4,5 Major histocompatibility complex (MHC) Class I expression might be such a cell surface marker with prognostic significance in endometrial cancer, exemplifying the role of the cellular immune system.All human body cells present antigens to the immune system by means of MHC Class I molecules on the cell surface. MHC Class I antigens comprise the classical (Class Ia) human leukocyte antigen (HLA)-A, -B and -C antigens and the nonclassical (Class Ib) HLA-E...

Status of cellular immunity lacks prognostic significance in vulvar squamous carcinoma

“…However, HLA class I downregulation did not have a significant influence on survival of patients with vulvar carcinoma. These results are in contrast to studies in endometrial [28], ovarian [33,34] and cervical cancer [31,35] where an association between downregulation of HLA class I and poor prognosis was observed.…”

“…For immunostaining, tissue microarray slides were first dewaxed and rehydrated. Methods and antibodies for immunostaining of CD8 + T-lymphocytes, Foxp3 + T-lymphocytes, HLA-B/C and β 2 m were used as previously reported [22,28]. For HLA-A and IDO, antigen retrieval was performed by microwave treatment; 15 min in citrate (pH 6.0) (HLA-A), and EDTA buffer (pH 8.0) (IDO).…”

NLRC5 expression in tumors and its role as a negative prognostic indicator in stage III non-small-cell lung cancer patients

“…These results indicated that as in normal immune situations, NLRC5 regulates MHC class I expression in human tumors. By analyzing the clinical data of 62 postoperative NSCLC stage III patients, it was determined that MHC class I and nuclear NLRC5 expression were independent predictors of poor survival, which was consistent with certain previous studies (7,21,22). In the present study, there was a high level of consistency among the 62 NSCLC patients, as they all underwent radical surgery and were diagnosed with stage III-N 2 NSCLC.…”

“…Furthermore, the nuclear expression was found to be correlated with MHC class I. MHC class I heavy chain loss has been validated in a previous study to be a predictor of patient survival (22); the present study demonstrated that the expression of NLRC5 in the nucleus acted as a negative prognostic indicator in NSCLC patients. Therefore NLRC5 and MHC class I may be used in conjunction with other independent prognostic factors in order to further stratify patients for adjuvant therapy.…”

Human leukocyte antigen‐G expression is associated with a poor prognosis in patients with esophageal squamous cell carcinoma

“…23 It has also been reported that the status of HLA-G expression or sHLA-G levels in plasma was correlated with certain clinicopathological parameters in malignancies such as hepatocellular carcinoma (HCC), 24,25 nonsmall-cell lung cancer (NSCLC), 15,26,27 breast cancer, 28 endometrial carcinoma, 29 B-cell chronic lymphocytic leukemia (B-CLL), 30 gastric carcinoma and colorectal cancer. 31,32 These studies indicated that HLA-G might serve as a clinical marker in the diagnosis or prediction of clinical outcomes for malignant diseases.…”