Molecular markers for recurrence and sensitivity to preoperative chemoradiotherapy in locally advanced rectal tumours

Abstract

Background: The objective of our study is to provide predictive markers of locally advanced rectal tumour sensitivity to preoperative chemoradiotherapy in order to identify tumours that present a high risk of recurrence after standard total mesorectal excision surgery and preoperative chemoradiotherapy, according to histological response and microsatellite allelic imbalance (AI).

Methods: Twenty-nine locally advanced tumours were included in the study and the genomic alterations and the tumour regression grade of paired rectal biopsies (before chemoradiotherapy) and carcinomas (after surgery) were assessed. Clinical and allelotyping data were analysed for local and distant recurrence.

Results: The global AI frequency significantly decreased from 47.4 to 20.3% (p < 0.01) after preoperative treatment. Preoperative chemoradiotherapy significantly induced the loss of cells bearing AI at 8 microsatellites: D18S61, D8S264, D1S305, D10S191, D4S394, D14S65, D17S790 and D10S192. Among these, AI at the D8S264 locus was significantly associated with recurrence in our rectal tumour cohort (p = 0.039).

Conclusion: Loss of AI at D8S264 is predictive of sensitivity to neoadjuvant treatment; thus, we concluded that the persistence of AI at D8S264 in rectal tumours after preoperative chemoradiotherapy could be considered a molecular marker of recurrence.