Correlation Between Biomarker Candidate Proteins with the Effect of Neoadjuvant Chemoradiation Therapy on Esophageal Squamous Cell Carcinoma

Ann Surg Oncol. 2018 Feb;25(2):449-455. doi: 10.1245/s10434-017-6271-y. Epub 2017 Nov 29.

Abstract

Background: While chemoradiation therapy (CRT) is one of the most useful treatments for esophageal squamous cell carcinoma (ESCC), it is important to predict response prior to treatment by using markers because some patients respond well and others do not.

Methods: Fifty-nine patients with ESCC were treated with neoadjuvant CRT at the Kagoshima University Hospital. The expression of seven types of biomarker candidate proteins in biopsy specimens of untreated primary tumors was evaluated to determine whether it correlated with response and prognosis.

Results: The positive expression rates were 47% for p53, 83% for CDC25B, 68% for 14-3-3sigma, 76% for p53R2, 75% for ERCC1, 32% for Gli-1, and 54% for Nrf2. In terms of histological response, tumor grade of the 59 patients was 48.8% for grade 1 as the non-responder, 29.2% for grade 2, and 22.0% for grade 3 as the responder. CRT was significantly effective in p53(-), p53R2(-), ERCC1(-), and Nrf2(-) tumors, while p53(-), p53R2(-), and ERCC1(-) were factors independently correlated with effective histological response. Their combined expression of two or three negative expressions had 100% effective response and was a significant prognostic factor.

Conclusion: Our results suggest that two or three negative expressions of p53, p53R2, and ERCC1 in biopsy specimens of primary tumors were associated with a favorable response to CRT for ESCC. Assessment of tumor suppressor and DNA repair protein expressions in biopsy specimens may be useful for the potential utility of CRT therapy for patients with ESCC prior to treatment.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / secondary*
  • Carcinoma, Squamous Cell / therapy
  • Chemoradiotherapy*
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology*
  • Esophageal Neoplasms / therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoadjuvant Therapy*
  • Neoplasm Invasiveness
  • Prognosis
  • Retrospective Studies
  • Survival Rate

Substances

  • Biomarkers, Tumor