Tissue microarray constructs to predict a response to chemoradiation in rectal cancer

Dig Liver Dis. 2010 Oct;42(10):679-84. doi: 10.1016/j.dld.2010.02.003. Epub 2010 Mar 15.

Abstract

Purpose: To identify, using tissue microarray (TMA), an immunohistochemical panel predictive of response to ionizing radiation (IR) in rectal cancer.

Methods: TMA constructs were prepared from archived stage II/III rectal tumors and matching adjacent mucosa (n=38) from patients treated with pre-operative chemoradiation. Immunohistochemistry (IHC) was performed for MIB, Cyclin E, p21, p27, p53, survivin, Bcl-2, and BAX. Immunoreactivity along with clinical variables was subjected to univariate and forward stepwise logistic regression analyses.

Results: Pathological complete response (pCR) was 23.9%. The number of positive lymph nodes obtained in the resected specimen was associated with pCR. Immunoreactivity for MIB (Sn 15%, Sp 65%, OR 0.33), p53 (Sn 3%, Sp 84%, OR 0.16), Bcl-2 (Sn 11%, Sp 74%, OR 0.35), and BAX (Sn 92%, Sp 80%, OR 46) was associated with pathological response (all p's<0.001). Forward stepwise logistic regression analysis demonstrated that MIB was an independent predictor of a response to chemoradiation (p=0.001).

Conclusions: A combined panel of mediators of apoptosis alone or combined with clinical factors is a feasible approach that can be applied to rectal tumor biopsies to predict a response to chemoradiation. The most sensitive factor was BAX; while MIB independently predicted a response to chemoradiation.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Diagnosis, Differential
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology*
  • Intestinal Mucosa / radiation effects
  • Male
  • Microarray Analysis / methods*
  • Middle Aged
  • Neoplasm Staging / methods*
  • Predictive Value of Tests
  • Radiotherapy, Adjuvant
  • Rectal Neoplasms / drug therapy
  • Rectal Neoplasms / genetics*
  • Rectal Neoplasms / radiotherapy
  • Treatment Outcome

Substances

  • Antineoplastic Agents