title: Phenotypic heterogeneity in hereditary non-polyposis colorectal cancer: identical germline mutations associated with variable tumour morphology and immunohistochemical expression.
abstract: BACKGROUND
  Hereditary non-polyposis colorectal cancer (HNPCC) is associated with high risks for colorectal and endometrial cancer, young age at onset and an increased risk of multiple primary tumours. Colorectal cancer in HNPCC is characterised by poor tumour differentiation, an expanding growth pattern, and a pronounced lymphocytic reaction with tumour-infiltrating lymphocytes.
  
  
  OBJECTIVE
  The mutation spectrum in HNPCC is diverse and in order to clarify whether the HNPCC tumour phenotype is influenced by the underlying genetic alteration, 29 colorectal cancers and 12 adenomas from 24 individuals in two HNPCC families were morphologically and immunohistochemically characterised.
  
  
  RESULTS
  The tumour morphology as well as the immunohistochemical expression of beta-catenin varied extensively within the families as well as between synchronous/metachronous colorectal cancers from the same individual. Poor tumour differentiation, an expanding growth pattern, and tumour-infiltrating lymphocytes occurred at higher frequencies in proximal tumours, whereas distal colorectal cancers often lacked distinct HNPCC-associated morphological features.
  
  
  CONCLUSIONS
  The clinical, morphological and immunohistochemical variability observed within these families indicates that other mechanisms than the underlying germline mutation influence the HNPCC phenotype. Since morphological features linked to HNPCC are less frequent in distal cancers, it may be particularly relevant to obtain family history and age of onset in these tumours in order to identify individuals with HNPCC.
authors.affiliation: Department of Pathology, Lund University Hospital, Lund, Sweden. britta.halvarsson@med.lu.se
authors.forename: Britta
authors.initials: B
authors.lastname: Halvarsson
authors.forename: Wolfram
authors.initials: W
authors.lastname: Müller
authors.forename: Maria
authors.initials: M
authors.lastname: Planck
authors.forename: Anna Clara
authors.initials: AC
authors.lastname: Benoni
authors.forename: Peter
authors.initials: P
authors.lastname: Mangell
authors.forename: Johan
authors.initials: J
authors.lastname: Ottosson
authors.forename: Magnus
authors.initials: M
authors.lastname: Hallén
authors.forename: Anna
authors.initials: A
authors.lastname: Isinger
authors.forename: Mef
authors.initials: M
authors.lastname: Nilbert
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D002454:Cell Differentiation; D002455:Cell Division; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D007124:Immunoenzyme Techniques; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D010641:Phenotype; D051176:beta Catenin / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D051176:beta Catenin