title: Distinct secreted Frizzled receptor protein 1 staining pattern in patients with hyperplastic polyposis coli syndrome.
abstract: BACKGROUND
  Patients with hyperplastic polyposis coli syndrome are thought to harbor precursor lesions of a proposed hyperplasia-carcinoma pathway in colorectal cancer, but morphologic recognition of such lesions remains difficult. Hypermethylation of the secreted Frizzled receptor protein 1 gene on chromosome 8p12 is one of the earliest molecular alterations in colorectal carcinogenesis, potentially disrupting the Wnt signaling cascade of cellular growth control.
  
  
  OBJECTIVE
  To determine if hyperplastic polyps from patients with hyperplastic polyposis coli syndrome show a distinct immunohistochemical expression pattern for mismatch repair proteins and secreted Frizzled receptor protein 1 compared to their sporadic counterparts.
  
  
  METHODS
  Immunohistochemical studies (secreted Frizzled receptor protein 1, 3 mismatch repair proteins, and p53) were performed on 23 hyperplastic polyps, 6 synchronous colon cancers, and normal colonic mucosa from 6 patients with hyperplastic polyposis coli syndrome and were compared with studies of sporadic hyperplastic polyps obtained from 13 matched control subjects.
  
  
  RESULTS
  The staining pattern for the mismatch repair proteins MLH-1, MSH-2, and MSH-6 did not differ between sporadic and syndromic hyperplastic polyps. In contrast, 52% of syndromic hyperplastic polyps showed a reproducible and distinct staining pattern for secreted Frizzled receptor protein 1 that was not seen in control specimens and that was associated with larger polyp size (P =.002) and location in the proximal colon (P =.01).
  
  
  CONCLUSIONS
  Some hyperplastic polyps from patients with hyperplastic polyposis coli syndrome show a secreted Frizzled receptor protein 1 immunophenotype that could indicate alterations of cellular growth control. These findings may help identify precursor lesions in the proposed hyperplasia-carcinoma pathway of colorectal carcinogenesis.
authors.affiliation: Institute of Pathology, University of Regensburg, Germany.
authors.forename: Barbara I
authors.initials: BI
authors.lastname: Oberschmid
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dietmaier
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Edgar
authors.initials: E
authors.lastname: Dahl
authors.forename: Eva
authors.initials: E
authors.lastname: Klopocki
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Beatty
authors.forename: Neil H
authors.initials: NH
authors.lastname: Hyman
authors.forename: Hagen
authors.initials: H
authors.lastname: Blaszyk
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000737:chemistry; D000368:Aged; D002352:Carrier Proteins; D003111:Colonic Polyps / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000032:analysis; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis* / Q000502:physiology; D044483:Intestinal Polyposis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000032:analysis; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D051153:Wnt Proteins; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D051153:Wnt Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins; C497172:MSH2 protein, human