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Originally published as Ann Surg Oncol Early Release 10.1245/ASO.2004.03.585 on November 12, 2004

Annals of Surgical Oncology 11:977-982 (2004)
© 2004 Society of Surgical Oncology
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ORIGINAL ARTICLES

Microsatellite Instability as a Prognostic Factor in Resected Colorectal Cancer Liver Metastases

Riad Haddad, MD, Robert T. Ogilvie, MD, FRCPC, Marina Croitoru, BSc, Victoria Muniz, MD, Robert Gryfe, MD, PhD, FRCSC, Aaron Pollet, MD, Preshanthini Shanmugathasan, BSc, Timothy Fitzgerald, MD, FRCSC, Calvin H. L. Law, MD, MPH, FRCSC, Sherif S. Hanna, MD, FRCSC, FACS, Serge Jothy, MD, PhD, FRCPC, Mark Redston, MD, FRCPC, Steven Gallinger, MD, MSc, FRCSC and Andrew J. Smith, MD, MSc, FRCSC, FACS

From the Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada (RH, MC, VM, RG, SG); University of Toronto, Toronto, Ontario, Canada (RH, RG, AP, TF, CHLL, SSH, MR, SG, AJS); Sunnybrook and Women’s Health Sciences Centre, Toronto, Ontario, Canada (RTO, PS, TF, CHLL, SSH, SJ, AJS); and Laboratory Medicine and Pathobiology, Mount Sinai Hospital, Toronto, Ontario, Canada (RTO, AP, MR).

Correspondence: Address correspondence and reprint requests to: Andrew J. Smith, MD, MSc, FRCSC, FACS, Sunnybrook and Women’s Health Sciences Centre, T-Wing, Room T2-057, 2075 Bayview Ave., Toronto, Ontario, Canada, M4N 3M5; Fax: 416-217-1338; E-mail: andy.smith{at}sw.on.ca

Background: Two distinct genetic mutational pathways characterized by either chromosomal instability or high-frequency microsatellite instability (MSI-H) are currently recognized in the pathogenesis of colorectal cancer (CRC). Recently, it has been shown that patients with primary CRC that displays MSI-H have a significant, stage-independent, multivariate survival advantage. Untreated CRC hepatic metastases are incurable and are associated with a median survival of 4 to 12 months. Conversely, surgical resection in selected patients results in a 20% to 50% cure rate. The aim of this study was to investigate the prognostic importance of MSI-H in patients undergoing resection of hepatic CRC metastases.

Methods: DNA was extracted from paraffin-embedded, resected metastatic CRC liver lesions and corresponding normal liver parenchyma from 190 patients. MSI-H status was determined by polymerase chain reaction–based evaluation of the noncoding mononucleotide repeats BAT-25 and BAT-26.

Results: MSI was detected in tumors from 5 (2.7%) of the 190 CRC patients. All MSI-H tumors were in patients with node-positive CRC primary tumors. The median survival after hepatic resection of MSI-H and non–MSI-H tumors was 67 and 61 months, respectively (P = .9).

Conclusions: These data suggest that MSI-H is not a common feature in resected CRC liver metastases and do not suggest a role for MSI in stratifying good versus poor prognosis in these patients.

Key Words: Microsatellite instability • Colorectal cancer • Hepatic metastases • Molecular markers




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