The use of molecular markers as a method to predict the response to neoadjuvant therapy for advanced stage rectal adenocarcinoma.

AIM: The response to combined neoadjuvant therapy for advanced stage rectal adenocarcinoma is predictive of outcome. In addition to both clinical and pathological features, the expression of a variety of molecules may provide another method of identifying tumour responsiveness to pre-operative therapy. The aim of this study was to evaluate several markers in the apoptotic pathway as well as expression of Cox-2 and vascular endothelial growth factor (VEGF) to determine their ability to predict response to neoadjuvant therapy.

METHOD: In total, 152 patients with advanced rectal adenocarcinoma were treated with neoadjuvant therapy followed by resection. Paraffin-embedded sections obtained before and after therapy were assessed by immunohistochemical staining for Cox-2, VEGF, p53, p21, p27, Bax, BCL-2 and apoptosis protease-activating factor 1 (APAF-1). These stains were correlated with tumour regression grade, complete pathological response and T-downstaging of the surgical specimen. Clinical and pathological data were also collected. Data were analysed using the χ2 and Spearman's correlation tests.

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 tumour regression grade (P<0.001), complete pathological response (P<0.031) and T-downstaging (P<0.004). On multivariate analysis, APAF-1 expression was found to be independently associated with good tumour regression grade. In contrast, overexpression of Cox-2 and VEGF in pretreatment biopsies was related to less tumour regression (P<0.003) and less likelihood of T-downstaging (P<0.03).

CONCLUSION: Immunohistochemical evaluation of initial biopsy specimens of rectal cancer with APAF-1, Cox-2 and VEGF may predict tumour response to neoadjuvant therapy in patients with advanced rectal adenocarcinoma. Those with an expected limited response may be considered for other investigational neoadjuvant protocols.