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

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Halvarsson, BrittaLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine (author)

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

Article/chapterEnglish2007

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2006-06-30
BMJ,2007

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LIBRIS-ID:oai:lup.lub.lu.se:b2a7d7b5-375c-47fd-8f22-db41679d96d3
https://lup.lub.lu.se/record/160139URI
https://doi.org/10.1136/jcp.2006.040402DOI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype

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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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Kirurgi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Surgery hsv//eng
HNPCC
histopathology
hereditary non-polyposis colorectal cancer
heterogeneity
MMR
mismatch-repair

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Müller, Wolfram (author)
Planck, MariaLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onk-mpl (author)
Benoni, Anna-ClaraLund University,Lunds universitet,Matrixbiologi,Forskargrupper vid Lunds universitet,Matrix Biology,Lund University Research Groups(Swepub:lu)med-a-b (author)
Mangell, PeterLund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups(Swepub:lu)kir-pma (author)
Ottosson, Johan (author)
Hallén, MagnusLund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)kir-mha (author)
Isinger Ekstrand, AnnaLund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH(Swepub:lu)onk-ais (author)
Nilbert, MefLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onk-mni (author)
TumörmikromiljöSektion I (creator_code:org_t)

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In:Journal of Clinical Pathology: BMJ60:7, s. 781-7861472-41460021-9746

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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