Molecular Predictors of Response to Neoadjuvant Chemoradiation for Rectal Cancer

Objectives: To determine whether the expression of specific molecular markers in the rectal cancer biopsies prior to treatment, can correlate with complete tumor response to chemoradiotherapy (CRT) as determined by the pathology of the surgical specimen. Methods: We retrospectively examined pretreatment rectal biopsies of patients aged 18 years or older with locally advanced rectal cancer who had been treated with neoadjuvant CRT and surgical resection in our tertiary-care, university-affiliated medical center, between January 2001 and December 2011. Samples were analyzed for expression of B-cell lymphoma 2, P53, Ki67, epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor, and the tumor regression grade after CRT and radical surgery. Results: Forty-seven patients were included in the final analysis. Main outcome measures were the correlation between the expression of the molecular markers tested in the pretreatment biopsy, and complete tumor response. Complete pathologic response after CRT was attained m 27% of the patients. Percentage of cells expressing EGFR in the pretreated biopsies of patients having complete pathologic response after CRT and surgery was 33.08 +/- 7.87% compared to 19 +/- 15.36% (P = 0.38), 6.66 +/- 2.83% (P < 0.003), and 12.5 +/- 4.93% (P = 0.033) in patients with partial response and tumor regression grades of 2, 3, and 4, respectively. The other molecular markers tested in the pretreatment biopsy did not corresponded with complete pathologic response. Conclusions: EGFR expression pattern in the pretreatment biopsies of rectal tumors can assist in identifying patients who will benefit from neoadjuvant CRT.