title: High levels of soluble MICA are significantly related to increased disease-free and disease-specific survival in patients with cervical adenocarcinoma.
abstract: 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 174.73 pg/ml and a median sHLA-G of 5.35 U/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.
authors: Department of Gynecology, Netherlands Cancer Institute - Antoni van Leeuwenhoek (in collaboratation within the Centre for Gynecologic Oncology Amsterdam (CGOA)), Amsterdam, the Netherlands.
authors: S
authors: S
authors: Samuels
authors: D M
authors: DM
authors: Ferns
authors: D
authors: D
authors: Meijer
authors: J P
authors: JP
authors: van Straalen
authors: M R
authors: MR
authors: Buist
authors: H J
authors: HJ
authors: Zijlmans
authors: G G
authors: GG
authors: Kenter
authors: E S
authors: ES
authors: Jordanova
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D018196:Carcinoma, Adenosquamous / Q000097:blood / Q000276:immunology / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D059951:HLA-G Antigens / Q000097:blood; D015395:Histocompatibility Antigens Class I / Q000097:blood*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000097:blood*; D009367:Neoplasm Staging; D011379:Prognosis; D012995:Solubility; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000276:immunology* / Q000401:mortality / Q000473:pathology
chemical_list: D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D009363:Neoplasm Proteins
keywords: adenocarcinoma; cervical cancer; soluble human leukocyte antigen G; soluble major histocompatibility complex class I chain-related molecule A; survival