The Use of Molecular Markers as a Method of Predicting Response to Combined Modality Therapy for Advanced Stage Rectal Cancers
ME Berho, SD Wexner. Cleveland Clinic Florida, Weston, FL
Background: Response to combined modality therapy (CMT) of advanced stage rectal cancers is predictive of outcome. In addition to clinical and pathologic features, expression of a variety of molecules may provide another method of identifying tumor responsiveness to CMT. Our study aim was to evaluate several markers in the apoptotic pathway as well as expression of COX-2 and VGEF to determine their ability to predict response to CMT.
Design: 152 patients with advanced rectal cancer treated with CMT followed by radical resection were included in the analysis. Paraffin-embedded sections obtained before and after therapy were assessed by immunohistochemical staining for COX-2, VGEF, p53, p21, p27, Bax, BCL2 and Apoptosis Protease-Activating Factor 1 (APAF-1) and correlated with tumor regression grade, complete pathological response and T-downstaging. Clinical and pathologic data was also collected. Data was analyzed using Chi-square and Spearman correlation.
Results: Pathological complete response was seen in 24.5% of patients. Amongst the apoptosis associated markers, only APAF-1 expression was found to be significantly associated with tumor regression grade (p<0.001), complete pathologic response (p<0.031), and T-downstaging (p<0.004). On multivariate analysis, APAF-1 expression was found to be independently associated with tumor regression grade. In contrast, overexpression of COX2 and VGEF in pre-treatment biopsies was related to less tumor regression (p<0.003) and less likelyhood of T-downstaging (p<0.03)
Conclusions: Immunohistochemical evaluation of initial biopsy specimens of rectal cancer with APAF-1, COX2 and VGEF may predict tumor response to CMT in patients with advanced rectal cancer Those with an expected limited response may be considered for other investigational neoadjuvant protocols.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 81, Tuesday Afternoon