title: Expression and immune responses to MAGE antigens predict survival in epithelial ovarian cancer.
abstract: The MAGE cancer-testis antigens (CTA) are attractive candidates for immunotherapy. The aim of this study was to determine the frequency of expression, humoral immunity and prognostic significance of MAGE CTA in human epithelial ovarian cancer (EOC). mRNA or protein expression frequencies were determined for MAGE-A1, -A3, -A4, -A10 and -C1 (CT7) in tissue samples obtained from 400 patients with EOC. The presence of autologous antibodies against the MAGE antigens was determined from 285 serum samples. The relationships between MAGE expression, humoral immunity to MAGE antigens, and clinico-pathologic characteristics were studied. The individual frequencies of expression were as follows: A1: 15% (42/281), A3: 36% (131/390), A4: 47% (186/399), A10: 52% (204/395), C1: 16% (42/267). Strong concordant expression was noted with MAGE-A1:-A4, MAGE-A1:-C1 and MAGE-A4:-A10 (p<0.0005). Expression of MAGE-A1 or -A10 antigens resulted in poor progression free survival (PFS) (OR 1.44, CI 1.01-2.04, p = 0.044 and OR 1.3, CI 1.03-1.64, p = 0.03, respectively); whereas, MAGE-C1 expression was associated with improved PFS (OR 0.62, CI 0.42-0.92, p = 0.016). The improved PFS observed for MAGE-C1 expression, was diminished by co-expression of MAGE-A1 or -A10. Spontaneous humoral immunity to the MAGE antigens was present in 9% (27/285) of patients, and this predicted poor overall survival (log-rank test p = 0.0137). These findings indicate that MAGE-A1, MAGE-A4, MAGE-A3, and MAGE-A10 are priority attractive targets for polyvalent immunotherapy in ovarian cancer patients.
authors.affiliation: Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Sayeema
authors.initials: S
authors.lastname: Daudi
authors.affiliation: Department of Biostatisticsm, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Kevin H
authors.initials: KH
authors.lastname: Eng
authors.affiliation: Department of Pathology, University Southern California, Los Angeles, California, United States of America.
authors.forename: Paulette
authors.initials: P
authors.lastname: Mhawech-Fauceglia
authors.affiliation: Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Carl
authors.initials: C
authors.lastname: Morrison
authors.affiliation: Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, New York, United States of America; Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Anthony
authors.initials: A
authors.lastname: Miliotto
authors.affiliation: Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Amy
authors.initials: A
authors.lastname: Beck
authors.affiliation: Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, New York, United States of America; Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Junko
authors.initials: J
authors.lastname: Matsuzaki
authors.affiliation: Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, New York, United States of America; Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Takemasa
authors.initials: T
authors.lastname: Tsuji
authors.affiliation: Department of Biostatisticsm, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Groman
authors.affiliation: Department of Medicine, Mount Sinai Hospital, New York, New York, United States of America.
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
authors.affiliation: Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Guillo
authors.initials: G
authors.lastname: Spagnoli
authors.affiliation: Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Shashikant
authors.initials: S
authors.lastname: Lele
authors.affiliation: Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, New York, United States of America; Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, New York, United States of America; Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Kunle
authors.initials: K
authors.lastname: Odunsi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D056724:Immunity, Humoral; D007150:Immunohistochemistry; D007167:Immunotherapy; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000951:Antigens, Neoplasm; D009363:Neoplasm Proteins
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