title: NY-ESO-1 expression predicts an aggressive phenotype of ovarian cancer.
abstract: NY-ESO-1 is a cancer testis antigen and a promising target for immunotherapy. The purpose of this study was to determine the expression frequency, immunogenicity, and clinical impact of NY-ESO-1 in ovarian cancer.
  
  
  
  Immunohistochemistry (IHC), reverse-transcription polymerase chain reaction (RT-PCR), and quantitative-PCR (qRT-PCR) were utilized in an ovarian cancer (including Fallopian tube and primary peritoneal cancers) patient cohort; humoral responses against NY-ESO-1 were determined by ELISA. Clinicopathologic outcomes including progression-free (PFS) and overall (OS) survival were evaluated based on NY-ESO-1 expression. Cohen's kappa (κ) tested agreement between expression tests.
  
  
  
  NY-ESO-1 expression was detected by any method in 40.7% of 1002 patients' tumors (NY-ESO-1+) and baseline humoral response was identified in 19.0% of 689 tested patients. NY-ESO-1+ patients were older (p<0.001), higher stage (85% stage III/IV vs. 76.4%, p=0.015), less likely to have a complete response to initial therapy (53.9% vs. 68.9%, p=0.002), had more serous histotype (74.5% vs. 66.9%, p=0.011), and had more grade 3 tumors (83.7% vs. 70.8%, p<0.001). There was a trend towards shorter PFS (22.2 vs. 25.0months, p=0.07) and significantly shorter OS (42.9 vs. 50.0months, p=0.003) among NY-ESO-1+ patients. A subset analysis of NY-ESO-1+ patients that received immunotherapy demonstrated improved OS by >2years (52.6 vs. 27.2months, p<0.001).
  
  
  
  This study is the first demonstration of an association between NY-ESO-1 expression and an aggressive cancer phenotype. The relatively high expression frequency of NY-ESO-1 in ovarian cancer patients coupled with the poor clinical outcomes in NY-ESO-1+ patients reveals an underappreciated need for targeted therapy against this antigen. In support, our study reveals that NY-ESO-1+ patients enrolled on immunotherapy trials targeting the antigen exhibited an improvement in OS.
authors.affiliation: Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, United States.
authors.forename: J Brian
authors.initials: JB
authors.lastname: Szender
authors.affiliation: Omniseq LLC, Buffalo, NY 14203, United States.
authors.forename: Antonios
authors.initials: A
authors.lastname: Papanicolau-Sengos
authors.affiliation: Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY 14263, United States.
authors.forename: Kevin H
authors.initials: KH
authors.lastname: Eng
authors.affiliation: Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY 14263, United States.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Miliotto
authors.affiliation: Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY 14263, United States.
authors.forename: Amit A
authors.initials: AA
authors.lastname: Lugade
authors.affiliation: Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
authors.affiliation: Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY 14263, United States.
authors.forename: Junko
authors.initials: J
authors.lastname: Matsuzaki
authors.affiliation: Omniseq LLC, Buffalo, NY 14203, United States.
authors.forename: Carl D
authors.initials: CD
authors.lastname: Morrison
authors.affiliation: Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, United States; Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY 14263, United States. Electronic address: kunle.odunsi@roswellpark.org.
authors.forename: Kunle
authors.initials: K
authors.lastname: Odunsi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000276:immunology*; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D010641:Phenotype; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D008565:Membrane Proteins