Predictive value of APAF-1 and COX-2 expression in pathologic complete response to neoadjuvant chemoradiotherapy for patients with locally advanced rectal adenocarcinoma

Oncotarget. 2016 Jun 7;7(23):35233-40. doi: 10.18632/oncotarget.9125.

Abstract

Purpose: To investigate predictive value of APAF-1 and COX-2 expression in pathologic complete response (pCR) for patients with rectal adenocarcinoma (RAC) who were treated with neoadjuvant chemoradiotherapy (neo-CRT) followed by total mesorectal excision (TME).

Materials and methods: Immunohistochemistry assay was used to detect expression of APAF-1 and COX-2 in paraffin-wax embedded tissues obtained before neo-CRT for patients with RAC. A 5-point tumor-regression grade (TRG) based on the ratio of residual tumor to fibrosis according to Dworak's scoring system was used to assess neo-CRT response. The relationship between expression of APAF-1 and COX-2 genes and pCR was explored.

Results: pCR (TRG4) was observed in 23 patients (28.0%). pCR were more likely to be achieved for those with APAF-1 over-expression or lower expression of COX-2. pCR rate in patients with combination of high APAF-1 and low COX-2 expression was 56.0%, significantly higher than those with other combination of APAF1 and COX-2 expression. Multivariate analysis showed that over-expression of APAF-1 and suppressed expression of COX-2 were independent predictive factors for pCR.

Conclusion: Immunohistochemical evaluation of APAF-1 and COX-2 expression on pretreatment specimen may be used to predict pCR to neo-CRT in patients with RAC. The potential of the markers in monitoring pCR patient merits further investigation.

Keywords: APAF-1; COX-2; complete pathological response; neoadjuvant chemoradiotherapy; rectal adenocarcinoma.

MeSH terms

  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / therapy
  • Adolescent
  • Adult
  • Aged
  • Apoptotic Protease-Activating Factor 1 / analysis
  • Apoptotic Protease-Activating Factor 1 / biosynthesis*
  • Biomarkers, Tumor / analysis*
  • Chemotherapy, Adjuvant
  • Cyclooxygenase 2 / analysis
  • Cyclooxygenase 2 / biosynthesis*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Predictive Value of Tests
  • Rectal Neoplasms / mortality
  • Rectal Neoplasms / pathology*
  • Rectal Neoplasms / therapy
  • Young Adult

Substances

  • APAF1 protein, human
  • Apoptotic Protease-Activating Factor 1
  • Biomarkers, Tumor
  • Cyclooxygenase 2
  • PTGS2 protein, human