Author of

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  OA19 - Translational Research in Early Stage NSCLC (ID 402)

  • Event: WCLC 2016
  • Type: Oral Session
  • Track: Early Stage NSCLC
  • Presentations: 1
  • Moderators:G. Heller, G. Goss
  • Coordinates: 12/07/2016, 11:00 - 12:30, Schubert 3

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    OA19.05 - High Oncofetal Chondroitin Sulfate Expression is an Independent Prognostic Factor of Poor Survival in Early-Stage NSCLC (ID 5601)

    11:45 - 11:55  |  Author(s): J.W. Allen
    • Abstract
    • Presentation
    • Slides

    Background:
    Most human cancers express proteoglycans modified with distinct oncofetal chondroitin sulfate (CS) chains that are normally restricted to placental tissue. Oncofetal CS chains can be conveniently detected and targeted by recombinant VAR2CSA (rVAR2) proteins derived from the malaria parasite Plasmodium falciparum. In the present study, we have analyzed the expression landscape of oncofetal CS modifications in early-stage non-small cell lung cancer (NSCLC).
    
    Methods:
    Tissue microarrays from four separate patient cohorts representing a total of 493 clinically annotated stage I-II NSCLC cases were stained for oncofetal CS using rVAR2. Data were analyzed for correlation between low and high oncofetal CS presentation by immunohistochemical (IHC) staining of tumor and stroma compartments in respect to EGFR and KRAS mutations, as well as to clinical characteristics including relapse-free survival (RFS) and overall survival (OS).
    
    Results:
    There were 351 patients with low (IHC score 0-1) and 142 with high (IHC score 2-3) expressing tumors. We identified 331 adenocarcinomas, 145 squamous cell carcinomas, and 12 cases with other NSCLC subtypes. There were 314 stage I and 179 stage II cases by AJCC 7[th] edition. High oncofetal CS expression was significantly associated with shorter RFS (vs. high expressiors; 58 vs. 39 months, respectively, p=0.034) and OS (vs. high expressors; 69 vs. 51 months, respectively, p=0.044). High oncofetal CS expression was significantly associated with shorter RFS vs. low expression in men (p=0.024), smokers (p=0.011), and in patients with squamous cell tumors (p=0.012). High oncofetal CS was also significantly associated with shorter OS in men (p=0.005) and smokers (p=0.028). There were no significant RFS or OS differences in oncofetal CS expressions when stratifying the patients according to their EGFR or KRAS statuses. In multivariate survival analyses, histology, stage, and high oncofetal CS expression was significantly associated with shorter RFS vs. high expression (HR, 1.8; 95% CI, 1.32–2.48; p < 0.001).
    
    Conclusion:
    This is the first study showing that high oncofetal CS expression is an independent prognostic factor of poor RFS in NSCLC and validates high oncofetal CS expression as a prognostic factor of poor OS. In contrast to non-smoker females, oncofetal CS appears to be a prognostic for OS in males and smokers. Our work promotes oncofetal CS as a candidate target for rVAR2-based therapeutic intervention in NSCLC patients with poor RFS/OS.
    
    

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