title: Prognostic impact of human leukocyte antigen class I expression and association of platinum resistance with immunologic profiles in epithelial ovarian cancer.
abstract: Epithelial ovarian cancer (EOC) is one of the most deadly carcinomas in females. Immune systems can recognize EOCs; however, a defect of human leukocyte antigen (HLA) class I expression is known to be a major mechanism for escape from immune systems, resulting in poor prognosis. The purpose of this study is to identify novel correlations between immunologic responses and other clinical factors. We investigated the expression of immunologic components in 122 cases of EOCs for which surgical operations were performed between 2001 and 2011. We immunohistochemically stained EOC specimens using an anti-pan HLA class I monoclonal antibody (EMR8-5) and anti-CD3, -CD4, and -CD8 antibodies, and we analyzed correlations between immunologic parameters and clinical factors. In multivariate analysis that used the Cox proportional hazards model, independent prognostic factors for overall survival in advanced EOCs included low expression level of HLA class I [risk ratio (RR), 1.97; 95% confidence interval (CI), 1.01-3.83; P = 0.046] and loss of intraepithelial cytotoxic T lymphocyte (CTL) infiltration (RR, 2.11; 95% CI, 1.06-4.20; P = 0.033). Interestingly, almost all platinum-resistant cases showed a significantly low rate of intraepithelial CTL infiltration in the χ(2) test (positive vs. negative: 9.0% vs. 97.7%; P < 0.001). Results from a logistic regression model revealed that low CTL infiltration rate was an independent factor of platinum resistance in multivariate analysis (OR, 3.77; 95% CI, 1.08-13.12; P = 0.037). Platinum-resistant EOCs show poor immunologic responses. The immune escape system of EOCs may be one of the mechanisms of platinum resistance.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan. mariya.tasuku@sapmed.ac.jp hirohash@sapmed.ac.jp torigoe@sapmed.ac.jp.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Mariya
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. mariya.tasuku@sapmed.ac.jp hirohash@sapmed.ac.jp torigoe@sapmed.ac.jp.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. mariya.tasuku@sapmed.ac.jp hirohash@sapmed.ac.jp torigoe@sapmed.ac.jp.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Asano
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kuroda
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Yasuda
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Mizuuchi
authors.affiliation: Department of Public Health, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sonoda
authors.affiliation: Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000077216:Carcinoma, Ovarian Epithelial; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D010984:Platinum / Q000494:pharmacology* / Q000627:therapeutic use; D011379:Prognosis; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents; D015395:Histocompatibility Antigens Class I; D010984:Platinum