Microsatellite instability & survival in patients with stage II/III colorectal carcinoma
Markovic Srdjan1, Antic Jadranka2, Dimitrijevic Ivan3, Zogovic Branimir4, Bojic Daniela1, Svorcan Petar1, Markovic Velimir5, Krivokapic Zoran6
1 Center for Gastroenterology and Hepatology, Zvezdara University Clinical Center; School of Medicine, University of Belgrade, Belgrade, Serbia
2 Genetic Laboratory, Institute for Endocrinology, Clinical Center of Serbia, Belgrade, Serbia
3 Center for Colorectal Surgery, Clinical Center of Serbia, Belgrade, Serbia
4 School of Medicine, University of Western Sydney, Campbelltown; New South Wales, Australia
5 Center for Colorectal Surgery, Clinical Center of Serbia; School of Medicine, University of Belgrade, Belgrade, Serbia
6 Genetic Laboratory, Institute for Endocrinology, Clinical Center of Serbia; School of Medicine, University of Belgrade, Belgrade, Serbia
Dimitrija Tucovica 161, 11000, Belgrade
Source of Support: None, Conflict of Interest: None
Background & objectives: The two key aspects associated with the microsatellite instability (MSI) as genetic phenomenon in colorectal cancer (CRC) are better survival prognosis, and the varying response to 5-fluorouracil (5-FU)-based chemotherapy. This study was undertaken to measure the survival of surgically treated patients with stages II and III CRC based on the MSI status, the postoperative 5-FU treatment as well as clinical and histological data.
Methods: A total of 125 consecutive patients with stages II and III (American Joint Committee on Cancer, AJCC staging) primary CRCs, were followed prospectively for a median time of 31 months (January 2006 to December 2009). All patients were assessed, operated and clinically followed. Tumour samples were obtained for cytopathological verification and MSI grading.
Results: Of the 125 patients, 21 (20%) had high MSI (MSI-H), and 101 patients (80%) had MSI-L or MSS (low frequency MSI or stable MSI). Patients with MSS CRC were more likely to have recurrent disease (P=0.03; OR=3.2; CI 95% 1-10.2) compared to those with MSI-H CRC. Multi- and univariate Cox regression analysis failed to show a difference between MSI-H and MSS groups with respect to disease-free, disease-specific and overall survival. However, the disease-free survival was significantly lower in patients with MSI-H CRC treated by adjuvant 5-FU therapy (P=0.03).
Interpretation & conclusions: MSI-H CRCs had a lower recurrence rate, but the prognosis was worse following adjuvant 5-FU therapy.