title: P53 and SOX2 Protein Expression Predicts Esophageal Adenocarcinoma in Response to Neoadjuvant Chemoradiotherapy.
abstract: The aim of the study was to investigate the association between p53, SOX2, and CD44 protein expression and tumor response, and to validate potential predictive biomarker(s) in an independent cohort.
  
  
  
  Neoadjuvant chemoradiotherapy (nCRT) followed by surgery has become a standard of care for esophageal adenocarcinoma (EAC). However, the response to nCRT is highly variable among patients.
  
  
  
  EAC patients who underwent nCRT and surgery, between January 2003 and December 2014 at the Erasmus University Medical Center, were included and divided into a primary (n = 77) and a validation cohort (n = 70). P53, SOX2, and CD44 expression was detected by immunohistochemistry in pretreatment tumor biopsies, and scored independently by 2 investigators. Response to nCRT was assessed based on tumor regression grade (TRG) in the resection specimen.
  
  
  
  Forty-one (53%) patients in the primary cohort and 33 (47%) patients in the validation cohort showed major response (TRG1 or TRG2) in the resection specimen. Aberrant p53 and absence of SOX2 were associated with major response in the primary cohort: adjusted odds ratio (OR) 6.3 [95% confidence interval (CI), 1.3-30.1) and adjusted OR 4.1 (95% CI, 1.4-12.4), respectively. The same was true for the validation cohort (p53: adjusted OR 8.6; 95% CI, 0.93-80.9 and SOX2: adjusted OR 6.1; 95% CI, 1.6-23.4). The highest probability of a major response was seen in patients with concurrent aberrant p53 and absence of SOX2 expression, with an OR of 6.7 (95% CI, 2.1-21.4) and 6.2 (95% CI, 1.8-21.2) in the primary and validation cohort.
  
  
  
  Pattern of p53 and particularly SOX2 protein expression in EAC predicts response to nCRT. These biomarkers may help to individualize treatment in EAC patients.
authors.affiliation: *Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, The Netherlands †Department of Pathology, Erasmus University Medical Center Rotterdam, The Netherlands ‡Department of Surgery, Erasmus University Medical Center Rotterdam, The Netherlands §Department of Medical Oncology, Erasmus University Medical Center Rotterdam, The Netherlands.
authors.forename: Sophie H
authors.initials: SH
authors.lastname: van Olphen
authors.forename: Katharina
authors.initials: K
authors.lastname: Biermann
authors.forename: Joel
authors.initials: J
authors.lastname: Shapiro
authors.forename: Bas P L
authors.initials: BP
authors.lastname: Wijnhoven
authors.forename: Eelke L A
authors.initials: EL
authors.lastname: Toxopeus
authors.forename: Ate
authors.initials: A
authors.lastname: van der Gaast
authors.forename: Hans A
authors.initials: HA
authors.lastname: Stoop
authors.forename: Jan J B
authors.initials: JJ
authors.lastname: van Lanschot
authors.forename: Manon C W
authors.initials: MC
authors.lastname: Spaander
authors.forename: Marco J
authors.initials: MJ
authors.lastname: Bruno
authors.forename: Leendert H J
authors.initials: LH
authors.lastname: Looijenga
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D059186:Chemoradiotherapy, Adjuvant; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D016629:Esophagectomy; D004947:Esophagus / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D012189:Retrospective Studies; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D016159:Tumor Suppressor Protein p53