High levels of soluble MICA are significantly related to increased disease-free and disease-specific survival in patients with cervical adenocarcinoma

作者：Samuels S; Ferns D M; Meijer D; van Straalen J P; Buist M R; Zijlmans H J; Kenter G G; Jordanova E S^*

来源：Tissue Antigens, 2015, 85(6): 476-483.

DOI：10.1111/tan.12562

• adenocarcinoma
• cervical cancer
• soluble human leukocyte antigen G
• soluble major histocompatibility complex class I chain-related molecule A
• survival

Downregulation of major histocompatibility complex class I chain-related molecule A (MICA) and upregulation of human leukocyte antigen G (HLA-G) on the tumor cells are important immune escape mechanisms for different epithelial tumors. In addition, upregulation of the soluble forms of the latter molecules in serum leads to peripheral T-cell and natural killer (NK)-cell tolerance. As for cervical cancer, it remains unknown whether soluble MICA (sMICA) and soluble HLA-G (sHLA-G) concentrations are related to tumor characteristics or patient survival rates. We measured sMICA and sHLA-G in pre-treatment sera of a large cohort of cervical cancer patients (n=366) by enzyme-linked immunosorbent assay (ELISA). We detected a median sMICA of 174.73pg/ml and a median sHLA-G of 5.35U/ml. We did not find an association between sHLA-G levels and clinicopathological characteristics. In adenocarcinoma, low sMICA concentration was positively related to recurrent disease, a higher International Federation of Gynecology and Obstetrics (FIGO) stage and vaginal involvement (Mann-Whitney U-test; P=0.018, P=0.042 and P=0.013, respectively). In the latter patient group, high sMICA levels were associated with better disease-free survival (DFS) and disease-specific survival (DSS) (P=0.011 and P=0.047). After adjusting for confounding factors, high sMICA proved to be an independent predictor for a better DFS and DSS [HR 0.16; 95% confidence interval (CI) 0.04-0.64; P=0.009 and HR 0.12; 95% CI 0.03-0.50; P=0.004]. sHLA-G did not influence survival in cervical cancer patients, regardless of histology. We conclude that cervical adenocarcinoma patients with high sMICA levels have an increased DFS and DSS. This data warrants a prospective trial to study the functional role of sMICA in cervical adenocarcinoma.

• 出版日期2015-6