Assessment of Molecular Biomarkers To Predict Response to Chemoradiation in Rectal Adenocarcinomas: A Tissue Microarray Based Study
P Kapur, D Saha, S Huerta. UT Southwestern Medical Center, Dallas, TX
Background: It is estimated that rectal cancer will affect 40,870 Americans in 2009. Preoperative chemoradiation has emerged as the standard treatment for patients with stage II and stage III rectal cancer. However, preoperative chemoradiation results in a wide spectrum of clinical response. Although standard pathologic features such as tumor grade and stage are important for the management of rectal cancer patients, they have limited ability to predict which patients will experience disease recurrence and/or progression. The purpose of this study was to identify an immunohistochemical panel predictive of response to ionizing radiation in rectal cancer.
Design: TMA constructs were prepared from surgically resected stage II/III rectal adenocarcinomas and matching adjacent mucosa from patients treated with preoperative chemoradiation (n = 46) between 2000 and 2008. Immunohistochemistry was performed, on residual viable tumors, for proteins associated with cell cycle (MIB-1, Cyclin E, p21, p27, and p53) and apoptosis (survivin, Bcl-2, and BAX). Immunoreactivity data were subjected to univariate and forward stepwise logistic regression analyses.
Results: Complete pathological response was seen in 8 patients (17.4%). These patients could not be assessed for immunoreactivity because there were no viable tumor cells. Good response (50%-99% reduction in tumor) was seen in 19 patients (41.3%). Poor response (<50% reduction in tumor) was seen in 19 patients (41.3%). Univariate analysis showed that the immunoreactivities for MIB-1 (OR 0.33, p < 0.001), p53 (OR 0.16, p < 0.001), Bcl-2 (OR 0.35, p < 0.001) were inversely associated with pathologic response; and the immunoreactivity for BAX (OR 46, p < 0.001) was directly associated with pathological response. Forward stepwise logistic regression analysis demonstrated that MIB-1 was an independent predictor of response to chemoradiation (p = 0.001).
Conclusions: The use of a panel of biomarkers associated with cell cycle (MIB-1, p53) and apoptosis (Bcl-2, BAX) may predict response to chemoradiation. Further prospective studies should be performed on preoperative biopsy samples of patients with rectal adenocarcinoma.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 86, Tuesday Afternoon