title: MAGE-A expression, immune microenvironment, and prognosis in upper urinary tract carcinoma.
abstract: The melanoma-associated antigen A (MAGE-A) family comprises cancer-testis antigens that represent promising prognostic biomarkers and immunotherapy targets in several cancer types. The aim of this study was to investigate the significance of MAGE-A expression in upper urinary tract urothelial carcinoma in relation to clinicopathological features, lymphocytic infiltration, and clinical outcome. We immunohistochemically examined the expression of MAGE-A in 171 patients with upper urinary tract urothelial carcinoma. High (≥ 50% positive) and low MAGE-A expression levels were observed in 33 (19%) and 49 (29%) cases, respectively. MAGE-A was negative in 89 cases (52%). MAGE-A expression was positively correlated with high histologic grade; concomitant carcinoma in situ; higher Ki-67 proliferation index; and infiltration of CD3-, CD8-, and CD45RO-positive T lymphocytes, but not with CD20-positive B lymphocytes. High MAGE-A expression was significantly associated with shorter metastasis-free survival after nephroureterectomy (log-rank P = .019; multivariate hazard ratio, 1.98; 95% confidence interval, 1.00-3.92). MAGE-A expression in metastatic lymph nodes was highly correlated with its expression in primary lesions. MAGE-A expression was retained in chemotherapy-resistant metachronous metastatic lesions of urothelial carcinoma. MAGE-A may be a promising prognostic biomarker and potential immunotherapeutic target for patients with upper urinary tract urothelial carcinoma.
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Makise
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. Electronic address: tmorikawa-tky@umin.ac.jp.
authors.forename: Teppei
authors.initials: T
authors.lastname: Morikawa
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ichimura
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Taketo
authors.initials: T
authors.lastname: Kawai
authors.affiliation: Department of Immunotherapeutics (Medinet), The University of Tokyo Hospital, Tokyo 113-0033, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Matsushita
authors.affiliation: Department of Immunotherapeutics (Medinet), The University of Tokyo Hospital, Tokyo 113-0033, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kakimi
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Kume
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000276:immunology* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating; D008297:Male; D058950:Melanoma-Specific Antigens / Q000032:analysis*; D008875:Middle Aged; D060787:Neoplasm Grading; D013997:Time Factors; D016896:Treatment Outcome; D059016:Tumor Microenvironment; D014571:Urologic Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy
chemical_list: D014408:Biomarkers, Tumor; D058950:Melanoma-Specific Antigens
keywords: Cancer-testis antigen; Immunohistochemistry; Immunotherapy; Survival; Urothelial carcinoma