Pathological complete response after
neoadjuvant chemoradiotherapy in locally advanced
rectal cancer patients is related to a favorable prognosis. The identification of early
biomarkers predictive of pathological complete response would help optimize the multimodality management of the patients. A panel of 11
tumor-related
proteins was investigated by immunohistochemistry in the pretreatment biopsy of a group of locally advanced
rectal cancer patients to identify early
biomarkers of pathological complete response to
neoadjuvant chemoradiotherapy. A mono-institutional retrospective cohort of 95 stage II/III locally advanced
rectal cancer patients treated with
neoadjuvant chemoradiotherapy and surgery was selected based on clinicalpathological characteristics and the availability of a pretreatment
tumor biopsy. Eleven selected
protein marker expression (MLH1, GLUT1, Ki67, CA-IX, CXCR4, COX2, CXCL12, HIF1,
VEGF, CD44, and RAD51) was investigated. The optimal cutoff values were calculated by receiver operating characteristic curve analysis. Classification and regression tree analysis was performed to investigate the
biomarker interaction. Patients presenting either Ki-67 or HIF1 or RAD51 below the cutoff value, or CXCR4 or COX2 above the cutoff value, were more likely to get a pathological complete response. Classification and regression tree analysis identified three groups of patients resulting from the combination of Ki-67 and CXCR4 expression. Patients with high expression of Ki-67 had the lowest chance to get a pathological complete response (18%), as compared to patients with low expression of both Ki-67 and CXCR4 (29%), and patients with low Ki-67 and high CXCR4 expression (70%). Pretreatment Ki-67, CXCR4, COX2, HIF1, and RAD51 in
tumor biopsies are associated with pathological complete response after
neoadjuvant chemoradiotherapy in locally advanced
rectal cancer. A combined evaluation of Ki-67 and CXCR4 would increase their predictive potential. If validated, their optimal cutoff could be used to select patients for a tailored multimodality treatment.