Prevalence and prognostic role of microsatellite instability in patients with rectal carcinoma

Background: Association between microsatellite instability (MSI) and favourable postoperative survival in patients with colorectal cancer receiving adjuvant chemotherapy has been indicated. To evaluate whether an analogous positive prognostic role of MSI could be present in rectal carcinoma (RC; most of RC patients received adjuvant radiotherapy), PCR-based microsatellite analysis of archival RCs and statistical correlation with clinico-pathological parameters were performed. Patients and Methods: DNA from paraffin-embedded paired samples of tumors and corresponding normal tissues from 91 RC patients was analyzed for MSI using five microsatellite markers (tumors were classified as MSI+ when > 2 markers were unstable). Results: Seventeen (19%) RC patients exhibited a MSI+ phenotype. Prevalence of instability was found in patients with earlier RC onset (28% in cases with diagnosis age <55 years vs. 15% in cases >55 years), whereas similar MSI frequencies were observed in patients with different disease stage or receiving different adjuvant therapies. While MSI was detected in 7 (64%) out of 11 familial patients, a remarkable lower MSI incidence was observed in sporadic cases (10/80; 12.5%). A significant association with better disease-free survival (DFS) and overall survival (OS) was found for MSI+ patients (median DFS/OS, 30/32 months) in comparison to MSI- ones (median DFS/OS, 18/21 months) (P <0.001). Conclusions: MSI was demonstrated to be a strong molecular prognostic marker in rectal carcinoma, independent on the administered treatment (radiotherapy, chemotherapy, or both).