Phenotypic heterogeneity in hereditary nonpolyposis colorectal cancer: identical germline mutations associated with variable tumor morphology and immunohistochemical expression.

Research output: Contribution to journalArticle


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. Aims and METHODS: 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.


Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
  • Surgery


  • HNPCC, histopathology, hereditary non-polyposis colorectal cancer, heterogeneity, MMR, mismatch-repair
Original languageEnglish
Pages (from-to)781-786
JournalJournal of Clinical Pathology
Issue number7
Publication statusPublished - 2007
Publication categoryResearch

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Oncology, MV (013035000), Surgery (013242200), Pathology, (Lund) (013030000), Surgery (Lund) (013009000), Department of Immunotechnology (011029300), Surgery Research Unit (013242220), Matrix biology (013212025)