Purpose: Pre-operative chemoradiation therapy (CRT) is standard treatment in clinical stage T3/4 or node positive rectal cancer, however, there are no established biomarker that can predict pathological response and clinical outcome to CRT. The aim of this study was to evaluate the correlation between expression of molecular markers and pathological response and clinical outcomes in patients with rectal cancer who received 5-FU based chemoradiotherapy. Experiment design: Immunohistochemical stain was performed in tissue arrays constructed from core tissue specimens taken before treatment and from operative specimens from 120 patients who received 5-FU based pre-operative CRT and surgery between June 2003 and Dec. 2008. Expression of Ki67, TS, BAX, EpCAM, p53, p21, EGFR, CD44, CD133, CD166, HIF1a and ALDH1 were assessed and correlated with tumor regression grades and disease free survival. Results Of 120 patients (M/F 77/43, median age:63), 23 (19.2%) patients achieved pathologic complete remission; Dworak grade 1: 18 (15%), grade 2: 51 (42.5%); Grade 3: 28 (23.3%), and Grade 4: 23 (19.2%). In the analysis of association between marker expressions and tumor regression grades, low p21 expression at pretreatment biopsy was significantly associated with grade 4 (total regression) (p=0.039) and better disease free survival (5yr DFS rate - low vs high p21: 89% vs 54%, p=0.001). In the multivariate analysis, low p21 expression level in pre-treatment biopsy was significantly associated with better DFS (p=0.003, HR 0.20; 95% CI 0.72, 0.57) and the score difference of p21 expression between pre- and post treatment tissue was also significant (p=0.002, HR 0.09; 95% CI 0.02, 0.39). Low CD166 expression level at pretreatment biopsy was associated with better DFS (p=0.003; HR 0.19; 95% CI 0.07, 0.58). Low ypN stage and high tumor regression grade also have significantly a good effect on DFS as well (p= 0.001, 0.018 respectively). Conclusion Our results showed low p21 and CD166 expression at pretreatment biopsy was associated with tumor regression and good prognosis in patients treated with 5-FU based chemoradioatherapy. Larger, prospective trials and functional studies are warranted to determine the role of p21 and CD166 as predictive biomarker of response to chemoradiotherapy.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4525. doi:1538-7445.AM2012-4525