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NY-ESO-1 expression predicts an aggressive phenotype of ovarian cancer

      Highlights

      • NY-ESO-1 is a common cancer-testis antigen expressed in ovarian cancer.
      • NY-ESO-1 expressing tumors portend an aggressive clinical course and early cancer-related death.
      • Antigen-targeted immunotherapy can overcome a harsh clinical phenotype.

      Abstract

      Objectives

      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.

      Methods

      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.

      Results

      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. 25.0 months, p = 0.07) and significantly shorter OS (42.9 vs. 50.0 months, p = 0.003) among NY-ESO-1+ patients. A subset analysis of NY-ESO-1+ patients that received immunotherapy demonstrated improved OS by >2 years (52.6 vs. 27.2 months, p < 0.001).

      Conclusions

      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.
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