Predictive immunohistochemical features for tumour response to chemoradiotherapy in rectal cancer

BACKGROUND: Reduced expression of cluster of differentiation (CD) 133 and cyclo-oxygenase (COX) 2, and increased density of CD8+ tumour-infiltrating lymphocytes, are associated with a favourable tumour response to preoperative chemoradiotherapy (CRT). This study aimed to evaluate these markers in relation to tumour response after preoperative CRT in two rectal cancer cohorts. METHODS: Patients with low rectal cancer who underwent radical resection and preoperative short-term CRT in 2001-2007 (retrospective cohort) and long-term CRT in 2011-2017 (prospective cohort) were analysed. Pretreatment biopsies were stained immunohistochemically using antibodies to determine CD133 and COX-2 expression, and increased CD8+ density. Outcome measures were tumour regression grade (TRG), tumour downstaging and survival. RESULTS: For 95 patients in the retrospective cohort, the incidence of TRG 3-4 was 67 per cent when two or three immunohistochemistry (IHC) features were present, but only 20 per cent when there were fewer features (P < 0.001). The incidence of tumour downstaging was higher in patients with at least two IHC features (43 versus 22 per cent with fewer features; P = 0.029). The 49 patients in the prospective cohort had similar rates to those in the retrospective cohort (TRG 3-4: 76 per cent for two or more IHC features versus 25 per cent with fewer features, P < 0.001; tumour downstaging: 57 versus 25 per cent respectively, P = 0.022). Local recurrence-free survival rates in patients with more or fewer IHC features were similar in the retrospective and prospective cohort (P = 0.058 and P = 0.387 respectively). CONCLUSION: Assessment of CD133, COX-2 and CD8 could be useful in predicting a good response to preoperative CRT in patients with lower rectal cancer undergoing neoadjuvant therapy. Further studies are needed to validate the results in larger cohorts and investigate a survival benefit.