Phenotypic heterogeneity in hereditary non-polyposis colorectal cancer: identical germline mutations associated with variable tumour morphology and immunohistochemical expression
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 pa...
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Published in | Journal of clinical pathology Vol. 60; no. 7; pp. 781 - 786 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
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London
BMJ Publishing Group Ltd and Association of Clinical Pathologists
01.07.2007
BMJ BMJ Publishing Group LTD BMJ Group |
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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. 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 β-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. |
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AbstractList | BACKGROUNDHereditary 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 METHODSThe 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.RESULTSThe 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.CONCLUSIONSThe 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. 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 {szligbeta}-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. 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 β-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. 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 β-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. 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. 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. 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. 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. |
Author | Halvarsson, Britta Hallén, Magnus Nilbert, Mef Müller, Wolfram Planck, Maria Benoni, Anna Clara Isinger, Anna Ottosson, Johan Mangell, Peter |
AuthorAffiliation | B Halvarsson , M Planck , A C Benoni , A Isinger , M Nilbert , Department of Pathology, Lund University Hospital, Lund, Sweden M Hallén , Department of Surgery, Lund University Hospital, Lund, Sweden W Müller , Gemeinschaftspraxis Pathologie Starnberg, Germany J Ottosson , Department of Surgery, Kristianstad Hospital, Kristianstad, Sweden P Mangell , Department of Surgery, Malmö University Hospital, Malmö, Sweden |
AuthorAffiliation_xml | – name: J Ottosson , Department of Surgery, Kristianstad Hospital, Kristianstad, Sweden – name: M Hallén , Department of Surgery, Lund University Hospital, Lund, Sweden – name: W Müller , Gemeinschaftspraxis Pathologie Starnberg, Germany – name: P Mangell , Department of Surgery, Malmö University Hospital, Malmö, Sweden – name: B Halvarsson , M Planck , A C Benoni , A Isinger , M Nilbert , Department of Pathology, Lund University Hospital, Lund, Sweden |
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Keywords | Immunohistochemistry Variable Hereditary non-polyposis colorectal cancer Genetic disease Heterogeneity Anatomic pathology Phenotype Association Germ line Morphology Digestive diseases Intestinal disease Genetics Tumor Mutation Lynch syndrome |
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Notes | href:jclinpath-60-781.pdf local:0600781 Correspondence to: Dr Britta Halvarsson Department of Pathology, Helsingborg Hospital, 251 87 Helsingborg, Sweden; Britta.Halvarsson@med.lu.se ark:/67375/NVC-1D0FPBX9-S istex:AE7E67263F0AE896873B327B9BD91B06899D9490 PMID:16901974 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
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Snippet | Background: Hereditary non-polyposis colorectal cancer (HNPCC) is associated with high risks for colorectal and endometrial cancer, young age at onset and an... Hereditary non-polyposis colorectal cancer (HNPCC) is associated with high risks for colorectal and endometrial cancer, young age at onset and an increased... Background: Hereditary non-polyposis colorectal cancer (HNPCC) is associated with high risks for colorectal and endometrial cancer, young age at onset and an... BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is associated with high risks for colorectal and endometrial cancer, young age at onset and an... BACKGROUNDHereditary non-polyposis colorectal cancer (HNPCC) is associated with high risks for colorectal and endometrial cancer, young age at onset and an... |
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SubjectTerms | Adenoma - genetics Adenoma - metabolism Adenoma - pathology adenomatous polyposis coli Adult Age Aged APC beta Catenin - metabolism Biological and medical sciences Cell Differentiation Cell Division Cloning Colorectal cancer Colorectal Neoplasms, Hereditary Nonpolyposis - genetics Colorectal Neoplasms, Hereditary Nonpolyposis - metabolism Colorectal Neoplasms, Hereditary Nonpolyposis - pathology Endometrial cancer Female Gastroenterology. Liver. Pancreas. Abdomen Germ-Line Mutation hereditary non-polyposis colorectal cancer heterogeneity histopathology HNPCC Humans Immunoenzyme Techniques Investigative techniques, diagnostic techniques (general aspects) Laboratories Lymphocytes Lymphocytes, Tumor-Infiltrating - pathology Male Medical sciences Middle Aged mismatch repair MMR Morphology Mutation Neoplasm Proteins - metabolism Original Ovarian cancer Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Phenotype Statistical analysis Stomach. Duodenum. Small intestine. Colon. Rectum. Anus TIL Tumors tumour-infiltrating lymphocytes |
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Title | Phenotypic heterogeneity in hereditary non-polyposis colorectal cancer: identical germline mutations associated with variable tumour morphology and immunohistochemical expression |
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