Universität zu Köln

Steinke, Verena, Holzapfel, Stefanie, Loeffler, Markus, Holinski-Feder, Elke, Morak, Monika, Schackert, Hans K., Goergens, Heike, Pox, Christian, Royer-Pokora, Brigitte, von Knebel-Doeberitz, Magnus, Buettner, Reinhard, Propping, Peter and Engel, Christoph ORCID: 0000-0002-7247-282X (2014). Evaluating the performance of clinical criteria for predicting mismatch repair gene mutations in Lynch syndrome: A comprehensive analysis of 3,671 families. Int. J. Cancer, 135 (1). S. 69 - 78. HOBOKEN: WILEY. ISSN 1097-0215

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Abstract

Carriers of mismatch repair (MMR) gene mutations have a high lifetime risk for colorectal and endometrial cancers, as well as other malignancies. As mutation analysis to detect these patients is expensive and time-consuming, clinical criteria and tumor-tissue analysis are widely used as pre-screening methods. The aim of our study was to evaluate the performance of commonly applied clinical criteria (the Amsterdam I and II Criteria, and the original and revised Bethesda Guidelines) and the results of tumor-tissue analysis in predicting MMR gene mutations. We analyzed 3,671 families from the German HNPCC Registry and divided them into nine mutually exclusive groups with different clinical criteria. A total of 680 families (18.5%) were found to have a pathogenic MMR gene mutation. Among all 1,284 families with microsatellite instability-high (MSI-H) colorectal cancer, the overall mutation detection rate was 53.0%. Mutation frequencies and their distribution between the four MMR genes differed significantly between clinical groups (p < 0.001). The highest frequencies were found in families fulfilling the Amsterdam Criteria (46.4%). Families with loss of MSH2 expression had higher mutation detection rates (69.5%) than families with loss of MLH1 expression (43.1%). MMR mutations were found significantly more often in families with at least one MSI-H small-bowel cancer (p < 0.001). No MMR mutations were found among patients under 40-years-old with only colorectal adenoma. Familial clustering of Lynch syndrome-related tumors, early age of onset, and familial occurrence of small-bowel cancer were clinically relevant predictors for Lynch syndrome.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Steinke, Verena UNSPECIFIED UNSPECIFIED UNSPECIFIED Holzapfel, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Loeffler, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Holinski-Feder, Elke UNSPECIFIED UNSPECIFIED UNSPECIFIED Morak, Monika UNSPECIFIED UNSPECIFIED UNSPECIFIED Schackert, Hans K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Goergens, Heike UNSPECIFIED UNSPECIFIED UNSPECIFIED Pox, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Royer-Pokora, Brigitte UNSPECIFIED UNSPECIFIED UNSPECIFIED von Knebel-Doeberitz, Magnus UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Propping, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Engel, Christoph UNSPECIFIED orcid.org/0000-0002-7247-282X UNSPECIFIED
URN:	urn:nbn:de:hbz:38-435301
DOI:	10.1002/ijc.28650
Journal or Publication Title:	Int. J. Cancer
Volume:	135
Number:	1
Page Range:	S. 69 - 78
Date:	2014
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1097-0215
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NONPOLYPOSIS COLORECTAL-CANCER; REVISED BETHESDA GUIDELINES; MICROSATELLITE INSTABILITY; MSH2; IMMUNOHISTOCHEMISTRY; IDENTIFICATION; DIAGNOSIS; CARRIERS; HNPCC Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43530