Abstract
Aberrant expression of human leukocyte antigens (HLA) class I has prognostic importance in various cancers. Here, we evaluated the prognostic value of classical (A/B/C) and nonclassical (G/E) HLA expression in 169 high grade epithelial ovarian cancer samples and linked that to clinicopathological characteristics and survival. Expression of HLA-A, -B/C, or -E was not correlated with survival. Survival was prolonged when tumours expressed HLA-G (P = 0.008) and HLA-G was an independent predictor for better survival (P = 0.011). In addition, HLA-G expression was associated with longer progression-free survival (P = 0.036) and response to chemotherapy (P = 0.014). Accordingly, high expression of HLA-G mRNA was associated with prolonged disease-free survival (P = 0.037) in 65 corresponding samples. Elevated serum-soluble HLA-G levels as measured by enzyme-linked immunosorbent assay in 50 matched patients were not correlated to HLA-G protein expression or gene expression nor with survival. During treatment, sHLA-G levels declined (P = 0.038). In conclusion, expression of HLA-G is an independent prognostic factor for improved survival in high grade epithelial ovarian cancer and a predictor for platinum sensitivity.
Highlights
Epithelial ovarian cancer (EOC) is the most lethal gynaecological cancer and the second cause of cancer related death among women [1]
Upregulation of human leukocyte antigens (HLA)-G expression was an independent predictor for improved survival
Our analyses showed that HLA-G expression in these tumours is correlated with residual disease after surgery and sensitivity to platinum chemotherapy
Summary
Epithelial ovarian cancer (EOC) is the most lethal gynaecological cancer and the second cause of cancer related death among women [1]. Result of debulking surgery, histological type, and response to chemotherapy all influence the prognosis [2,3,4]. All patients are treated with cytoreductive surgery and adjuvant combination chemotherapy, usually consisting of paclitaxel and carboplatin. Response to treatment is high, approximately 70% of patients with advanced disease develop recurrence, suggesting that effectiveness of treatment protocols is low. And histologically, there are large differences within epithelial ovarian cancer, suggesting different patterns of development. Type I tumours are low grade, are slowly growing, and develop from premalignant stage towards malignant lesion, while type II tumours are high grade, more aggressively growing, and often present at an advanced stage [6,7,8]. Even within type II tumours, large differences exist regarding response to treatment and patient survival
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