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Non-classical HLA-class I expression in serous ovarian carcinoma: Correlation with the HLA-genotype, tumor infiltrating immune cells and prognosis.

ABSTRACT: In our previous studies, we have shown that patients with serous ovarian carcinoma in advanced surgical stage disease have a particularly poor prognosis if they carry the HLA-A*02 genotype. This represent a stronger prognostic factor than loss or downregulation of the MHC class I heavy chain (HC) on tumor cells. In this study, we investigated the expression of the non-classical, immune tolerogenic HLA -G and -E on the tumor cells along with the infiltration of immune cells in the tumor microenvironment. FFPE primary tumors from 72 patients with advanced stages of serous adenocarcinoma and metastatic cells present in ascites fluid from 8 additional patients were included in this study. Both expression of HLA-G and aberrant expression of HLA-E were correlated to a significant worse prognosis in patients with HLA-A*02, but not with different HLA genotypes. Focal cell expression of HLA-G correlated to a site-specific downregulation of classical MHC class I HC products and aberrant HLA-E expression, showing a poor survival. HLA-G was more frequently expressed in metastatic cells than in primary tumor lesions and the expression of HLA-G inversely correlated with the frequency of tumor infiltrating immune cells. All these parameters can contribute together to identify and discriminate subpopulations of patients with extremely poor prognosis and can give them the opportunity to receive, and benefit of individually tailored treatments.

SUBMITTER: Andersson E

PROVIDER: S-EPMC4760332 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Non-classical HLA-class I expression in serous ovarian carcinoma: Correlation with the HLA-genotype, tumor infiltrating immune cells and prognosis.

Andersson Emilia E Poschke Isabel I Villabona Lisa L Carlson Joseph W JW Lundqvist Andreas A Kiessling Rolf R Seliger Barbara B Masucci Giuseppe V GV

Oncoimmunology 20150725 1

In our previous studies, we have shown that patients with serous ovarian carcinoma in advanced surgical stage disease have a particularly poor prognosis if they carry the HLA-A*02 genotype. This represent a stronger prognostic factor than loss or downregulation of the MHC class I heavy chain (HC) on tumor cells. In this study, we investigated the expression of the non-classical, immune tolerogenic HLA -G and -E on the tumor cells along with the infiltration of immune cells in the tumor microenvi ...[more]

PMID: 26942060

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Project description:PurposeThe survival duration of elderly patients with epithelial ovarian carcinoma is shorter than that of their younger counterparts. This variation in survival duration is likely attributed to differences in the distribution of histological type or grade, International Federation of Gynecology and Obstetrics (FIGO) staging, and undertreatment, but this observation remains controversial. This study aimed to investigate the biological factors other than selection bias associated with the decreased survival of elderly patients with ovarian carcinoma.MethodsA total of 314 serous ovarian cancer (SOC) patients from Jiangsu Institute of Cancer Research (JICR, PRC) between 2002 and 2012 were retrospectively analyzed, and 774 cases from MD Anderson Cancer Center (MDACC, USA) between 1992 and 2012 were used for validation. The 8-hydroxy-2'-deoxyguanine (8-OHdG) concentration in leukocyte DNA was evaluated by using commercially available enzyme-linked immunosorbent assay kits, and tissue expression was assayed through immunohistochemistry. The associations between survival durations and covariates were assessed by using a Cox proportional hazards model and by conducting a log-rank test.ResultsAdvanced age ≥ 65 years was correlated with high histological grade (p = 0.02), performance status (p = 0.03), primary treatment (p = 0.00), and suboptimal surgery outcome (p = 0.04) in SOC patients from JICR. Age, FIGO stage, histological grade, and optimal surgery were independently associated with the progression-free survival (PFS; p = 0.03, p = 0.03, p = 0.02, and p = 0.04, respectively) and overall survival (OS; p = 0.02, p = 0.04, p = 0.02, and p = 0.02, respectively) of the SOC patients from JICR. The 8-OHdG concentration in the leukocyte DNA was higher in the elderly patients than in the younger cases. The high 8-OHdG concentration in the leukocyte DNA indicated poorer median OS (30.0 months, confidence interval [CI]: 23.5-36.5 vs. 42.8 months, [CI] 38.3-47.2) and PFS (14.6 months, [CI] 11.9-17.2 vs. 18.9 months, [CI] 14.4-23.4) than those of their corresponding counterparts in the SOC patients who achieved a clinical complete response from primary treatment.ConclusionsCompared with younger cases, elderly patients with SOC were commonly characterized by high tumor grade, poor performance status, and undertreatment. High 8-OHdG concentration in leukocyte DNA was associated with advanced age and poor prognosis in SOC patients.

Dataset Information

Non-classical HLA-class I expression in serous ovarian carcinoma: Correlation with the HLA-genotype, tumor infiltrating immune cells and prognosis.

Publications

Non-classical HLA-class I expression in serous ovarian carcinoma: Correlation with the HLA-genotype, tumor infiltrating immune cells and prognosis.

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