title: Activation of pro-oncogenic pathways in colorectal hyperplastic polyps.
abstract: BACKGROUND
  In contrast to sessile serrated adenomas and traditional serrated adenomas which are associated with a significant cancer risk, the role of hyperplastic polyps (HP) in colorectal carcinogenesis as well as the molecular mechanisms underlying their development remain controversial and still need to be clarified. Several reports suggest that a subset of HP may represent precursor lesions of some colorectal cancers. However, biomarkers are needed to identify the subset of HP that may have a malignant potential. The hormone precursor, progastrin (PG) has been involved in colon carcinogenesis and is known to activate pro-oncogenic pathways such as the ERK or the STAT3 pathway. We therefore analyzed PG expression and the activation of these signaling factors in HP.
  
  
  METHODS
  We retrospectively analyzed PG expression as well as the phosphorylation of ERK and STAT3 by immunohistochemistry in HP from 48 patients.
  
  
  RESULTS
  Mean percentages of epithelial cells positive for PG or phospho-ERK were respectively, 31% and 33% in HP and were significantly higher in these lesions compared to normal colon (3%, p=0.0021 and 7%, p=0.0008, respectively). We found a significant correlation between PG and phospho-ERK expression in HP with ERK activation significantly stronger in lesions with high progastrin expression (p=0.015). In contrast, STAT3 was not significantly activated in HP compared to normal colon and we did not observe a significant correlation with PG expression.
  
  
  CONCLUSIONS
  HP overexpressing PG that have the highest activation of the ERK pathway might reflect less latent lesions that might have a malignant potential.
authors.forename: Catherine
authors.initials: C
authors.lastname: Do
authors.forename: Claudine
authors.initials: C
authors.lastname: Bertrand
authors.forename: Julien
authors.initials: J
authors.lastname: Palasse
authors.forename: Marie-Bernadette
authors.initials: MB
authors.lastname: Delisle
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cohen-Jonathan-Moyal
authors.affiliation: INSERM UMR,1037-Cancer Research Center of Toulouse (CRCT), Université Paul Sabatier, 31052 Toulouse cedex III, Toulouse, France. cathy.seva@inserm.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Seva
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003111:Colonic Polyps / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D005755:Gastrins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D005755:Gastrins; D015513:Oncogene Proteins; D011498:Protein Precursors; D050796:STAT3 Transcription Factor; C013706:big gastrin; D048049:Extracellular Signal-Regulated MAP Kinases