title: DNA mismatch repair abnormalities in acinar cell carcinoma of the pancreas: frequency and clinical significance.
abstract: OBJECTIVE
  Acinar cell carcinoma (ACC), including its mixed variants, is a rare pancreatic malignancy. Recent reports have documented its occurrence in Lynch syndrome. Our aim was to evaluate the frequency and clinicopathologic significance of DNA mismatch repair (MMR) deficiency in ACCs in general.
  
  
  METHODS
  Mismatch repair protein expression was evaluated by immunohistochemistry in a series of 36 ACC cases that were treated at our institution and had sufficient clinical information and pathologic material.
  
  
  RESULTS
  Loss of MMR protein was observed in 5 ACCs (5/36, 14%): 2 lost MLH1/PMS2, 2 lost MSH2/MSH6, and 1 lost MSH6 alone. The 1 MSH6-deficient case and 1 of the 2 MSH2/MSH6-deficient cases had a known history of Lynch syndrome, carrying a germline mutation in MSH6 and MSH2, respectively. None of the 5 tumors showed distinctive morphology. Two of the 5 patients died of disease 6 and 21 months after diagnosis. In contrast, in the MMR-normal group, only 1 of 30 patients died of disease (median follow-up, 32.5 months).
  
  
  CONCLUSIONS
  Mismatch repair protein deficiency is not uncommon in ACCs, occurring in 14% of the cases in this series. The MMR-deficient ACCs did not show distinctive morphologic features and were clinically no less aggressive than MMR-normal ACCs.
authors: From the Departments of *Pathology, †Biostatistics, and ‡Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors: Weiguo
authors: W
authors: Liu
authors: Jinru
authors: J
authors: Shia
authors: Mithat
authors: M
authors: Gönen
authors: Maeve A
authors: MA
authors: Lowery
authors: Eileen M
authors: EM
authors: O'Reilly
authors: David S
authors: DS
authors: Klimstra
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000032:analysis / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018267:Carcinoma, Acinar Cell / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000556:secondary; D002648:Child; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D053843:DNA Mismatch Repair; D045643:DNA Repair Enzymes / Q000032:analysis / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics; D005192:Family Health; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000032:analysis / Q000235:genetics; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000556:secondary; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes