A prospective clinical trial to evaluate mesothelin as a biomarker for the clinical management of patients with esophageal adenocarcinoma Journal Article


Authors: Byun, A. J.; Grosser, R. A.; Choe, J. K.; Rizk, N. P.; Tang, L. H.; Molena, D.; Tan, K. S.; Restle, D.; Cheema, W.; Zhu, A.; Gerdes, H.; Markowitz, A. J.; Bains, M. S.; Rusch, V. W.; Jones, D. R.; Adusumilli, P. S.
Article Title: A prospective clinical trial to evaluate mesothelin as a biomarker for the clinical management of patients with esophageal adenocarcinoma
Abstract: OBJECTIVE: To investigate the utility of serum soluble mesothelin-related peptide (SMRP) and tumor mesothelin expression in the management of esophageal adenocarcinoma (ADC). BACKGROUND: Clinical management of esophageal ADC is limited by a lack of accurate evaluation of tumor burden, treatment response, and disease recurrence. Our retrospective data showed that tumor mesothelin and its serum correlate, SMRP, are overexpressed and associated with poor outcomes in patients with esophageal ADC. METHODS: Serum SMRP and tumoral mesothelin expression from 101 patients with locally advanced esophageal ADC were analyzed before induction chemoradiation (pretreatment) and at the time of resection (posttreatment), as a biomarker for treatment response, disease recurrence, and overall survival (OS). RESULTS: Pre and posttreatment serum SMRP was ≥1 nM in 49% and 53%, and pre and post-treatment tumor mesothelin expression was >25% in 35% and 46% of patients, respectively. Pretreatment serum SMRP was not significantly associated with tumor stage ( P = 0.9), treatment response (radiologic response, P = 0.4; pathologic response, P = 0.7), or recurrence ( P =0.229). Pretreatment tumor mesothelin expression was associated with OS (hazard ratio: 2.08; 95% CI: 1.14-3.79; P = 0.017) but had no statistically significant association with recurrence ( P = 0.9). Three-year OS of patients with pretreatment tumor mesothelin expression of ≤25% was 78% (95% CI: 68%-89%), compared with 49% (95% CI: 35%-70%) among those with >25%. CONCLUSIONS: Pretreatment tumor mesothelin expression is prognostic of OS for patients with locally advanced esophageal ADC, whereas serum SMRP is not a reliable biomarker for monitoring treatment response or recurrence. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Keywords: retrospective studies; prospective study; prospective studies; adenocarcinoma; neoplasm recurrence, local; pathology; peptide; retrospective study; tumor marker; tumor recurrence; peptides; mesothelioma; mesothelin; gpi-linked proteins; glycosylphosphatidylinositol anchored protein; humans; human; biomarkers, tumor; adenocarcinoma of esophagus
Journal Title: Annals of Surgery
Volume: 278
Issue: 5
ISSN: 0003-4932
Publisher: Lippincott Williams & Wilkins  
Date Published: 2023-11-01
Start Page: e1003
End Page: e1010
Language: English
DOI: 10.1097/sla.0000000000005885
PUBMED: 37185875
PROVIDER: scopus
PMCID: PMC10593105
DOI/URL:
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Prasad S. Adusumilli -- Source: Scopus
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MSK Authors
  1. Hans Gerdes
    176 Gerdes
  2. Valerie W Rusch
    865 Rusch
  3. Arnold J Markowitz
    138 Markowitz
  4. Laura Hong Tang
    447 Tang
  5. Manjit S Bains
    338 Bains
  6. David Randolph Jones
    417 Jones
  7. Daniela   Molena
    272 Molena
  8. Kay See   Tan
    241 Tan
  9. Amy Zhu
    8 Zhu
  10. Waseem Cheema
    9 Cheema
  11. David Joseph Restle
    4 Restle
  12. Jennie Kim Choe
    10 Choe
  13. Alexander J Byun
    7 Byun