title: Genetic markers of malignant transformation in intraductal papillary mucinous neoplasm of the pancreas: a meta-analysis.
abstract: OBJECTIVE
  The objective of this study was to determine the relationship between specific genetic alterations and malignant transformation in intraductal papillary mucinous neoplasm (IPMN) of the pancreas.
  
  
  METHODS
  Quantitative meta-analysis was conducted of studies through October 2010 that adhered to the 1996 World Health Organization guidelines for distinguishing adenoma and borderline IPMN versus carcinoma in surgically resected specimens using a random-effects model. We developed a 6-point scoring system to assess study quality.
  
  
  RESULTS
  Thirty-nine studies (1235 IPMN samples) satisfied the inclusion criteria, and we conducted pooled analysis of 8 genetic markers: MUC1, MUC2, MUC5AC, kRas, p53, hTERT (human telomerase reverse transcriptase), cyclooxygenase 2, and Shh (Sonic hedgehog). Markers having the strongest association with malignant IPMN were hTERT (odds ratio [OR], 11.4; 95% confidence interval [CI], 3.5-36.7) and Shh (OR, 6.9; 95% CI, 2.4-20.2), whereas MUC5AC (OR, 1.0; 95% CI, 0.1-13.9) and kRas (OR, 2.0; 95% CI, 1.0-4.3) showed weak association with IPMN histologic progression.
  
  
  CONCLUSIONS
  Expression of hTERT is strongly associated with malignant transformation in IPMN, consistent with up-regulation of hTERT as a key step in progression of IPMN to cancer. Expression of kRas and MUC5AC is common but not strongly associated with IPMN histologic progression. The quality criteria used here may guide future reporting of genetic markers related to malignant transformation of IPMN.
authors: Division of Gastroenterology and Hepatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors: Sahar
authors: S
authors: Nissim
authors: Gregory E
authors: GE
authors: Idos
authors: Bechien
authors: B
authors: Wu
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000175:diagnosis / Q000235:genetics*; D000236:Adenoma / Q000175:diagnosis; D014408:Biomarkers, Tumor / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000175:diagnosis / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005819:Genetic Markers; D053823:Hedgehog Proteins; D006801:Humans; D055271:Mucin 5AC / Q000235:genetics; D018396:Mucin-1 / Q000235:genetics; D055262:Mucin-2 / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D019098:Telomerase / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers; D053823:Hedgehog Proteins; C117307:KRAS protein, human; C060192:MUC1 protein, human; C524625:MUC2 protein, human; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D018396:Mucin-1; D055262:Mucin-2; D011518:Proto-Oncogene Proteins; C509239:SHH protein, human; D016159:Tumor Suppressor Protein p53; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C509186:TERT protein, human; D019098:Telomerase; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins