Defective DNA Mismatch Repair in Long-Term (≥3 Years) Survivors with Pancreatic CancerMaple J.T. · Smyrk T.C. · Boardman L.A. · Johnson R.A. · Thibodeau S.N. · Chari S.T.
aDepartment of Internal Medicine, bDivision of Gastroenterology, cDepartment of Laboratory Medicine and Pathology, dDivision of Anatomic Pathology, and eDivision of Experimental Pathology and Laboratory Medicine, Mayo Clinic and Foundation, Rochester, Minn., USA
Background/Aims: Defective DNA mismatch repair (MMR) in pancreatic cancer, reported in up to 13% of sporadic pancreatic cancers, may predict a good prognosis. To determine if long-term survival in pancreatic cancer could be attributed to defective DNA MMR, we ascertained its prevalence in 35 pancreatic cancer patients who survived ≧3 years after surgery. Methods: We performed immunohistochemistry (IHC) for MMR proteins hMLH1, hMSH2, and hMSH6 in all 35 tumors and microsatellite instability (MSI) studies in 34/35 tumors using 10 microsatellite markers in paired normal and tumor DNA. Defective DNA MMR was defined as absence of protein expression on IHC and/or MSI in ≧30% of markers studied. Results: On IHC, 3/35 (8.6%) tumors had defective DNA MMR. All 3 had absent expression of a DNA MMR protein (hMLH1 in 2 and hMSH2) and 2/3 also had MSI; the third could not be tested. Definitely 2, and probably all 3 patients had hereditary nonpolyposis colon cancer as determined by clinical and genetic profiles. Conclusion: Defective DNA MMR is uncommon in long-term survivors of pancreatic cancer and does not account for the survival benefit in those with sporadic pancreatic cancer.