[1779] DNA Mismatch Repair Deficiency in Acinar Cell Carcinoma of the Pancreas: Frequency and Significance

Weiguo Liu, Jinru Shia, Eileen M O'Reilly, Maeve A Lowery, Peter J Allen, David S Klimstra. Memorial Sloan-Kettering Cancer Center, New York, NY

Background: Acinar cell carcinoma (ACC) is a rare pancreatic exocrine malignancy, accounting for about 1%-2% of all pancreatic cancer diagnoses. The molecular features of ACC remain to be fully characterized. Two recent reports from our institution have indicated the occurrence of ACC in the context of Lynch syndrome (LS). The frequency and clinical implication of DNA mismatch repair (MMR) deficiency in ACC, however, have not been systematically analyzed. The aim of this study was to evaluate the frequency and biological implications of MMR deficiency in ACCs treated at our institution.
Design: Patients diagnosed of ACCs who were surgically treated at our institution and whose tumor blocks were available for study were analyzed. Tumors with a minor secondary component (ductal or neuroendocrine) were included. Pancreatoblastomas were excluded. MMR protein expression was evaluated by IHC using antibodies against MLH1, MSH2, MSH6, and PSM2; the results were correlated with clinicopathologic features.
Results: Twenty-two patients fulfilled the inclusion criteria, 4 females and 18 males, ranging in age from 47 to 80 years (median, 64 years). Tumor location was the head of pancreas in 50% of the cases, and tumor size ranged from 1.8 to 27cm (mean, 6.9cm). Most patients (13/18, 72%) presented with stage II disease. With a median follow up of 31.5 months, the median recurrence-free survival was 13.5 months. IHC detected loss of MMR protein in 4 cases (18%): 2 lost both MLH1 and PMS2, and 2 lost both MSH2 and MSH6. The 2 MLH1/PMS2 deficient cases occurred in males, age 55 and 75 years respectively with no known history suggestive of LS. Of the 2 MSH2/MSH6 deficient cases, one was a 49-yr-old male from a known LS family that carried a germline mutation in MSH2. The second was a 74-yr-old female whose paternal grandfather also had pancreas cancer; no LS work-up was done in this patient. All 4 MMR abnormal tumors occurred in the body/tail of the pancreas with a mean tumor size of 9.6 cm. All 4 patients presented with stage II disease; 2 patients recurred at 14 and 27 months after resection.
Conclusions: MMR abnormality is not uncommon in ACCs, occurring in 18% of this consecutive series. In addition to reaffirming previous observations that ACC can occur in LS individuals and manifest the patient's underlying genetic defect, our findings suggest that MMR deficiency may also occur as a sporadic event in ACCs similar to colorectal and other types of tumors, thus providing directions for further research efforts.
Category: Pancreas

Tuesday, March 5, 2013 9:30 AM

Poster Session III # 215, Tuesday Morning


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