Engel, C. and Forberg, J and Holinski-Feder, E and Pagenstecher, C and Plaschke, J and Kloor, M and Poremba, C and Pox, CP and Ruschoff, J and Keller, G and Dietmaier, Wolfgang and Ruemmele, Petra and Friedrichs, N and Mangold, E and Buettner, R and Schackert, HK and Kienle, P and Stemmler, S and Moeslein, G and Loeffler, M (2006) Novel strategy for optimal sequential application of clinical criteria, immunohistochemistry and microsatellite analysis in the diagnosis of hereditary nonpolyposis colorectal cancer. INTERNATIONAL JOURNAL OF CANCER, 118 (1). pp. 115-122. ISSN 0020-7136,
Full text not available from this repository. (Request a copy)Abstract
Clinical criteria, microsatellite analysis (MSA) and immunohistochemistry (IHC) are important diagnostic tools for identification of hereditary nonpolyposis colorectal cancer (HNPCC) patients who are likely to carry pathogenic germline mutations in mismatch repair genes. Based on MSA and IHC results and subsequent mutation analyses of 1,119 unrelated index patients meeting the Amsterdam II criteria or the classical Bethesda guidelines, we analyzed the value of these tools to predict MLH1 and MSH2 mutations with the aim of establishing optimal strategies for their most efficient sequential use. The overall prevalence of pathogenic germline mutations in our cohort was 20.6% (95% CI = 18.3-23.0%) and 61.8% (95% CI = 56.8-66.6%), respectively, after MSA/IHC-based preselection. IHC was highly predictive (99.1%) and specific (99.6%) with regard to MSA. However, 14 out of 230 mutations (6%) escaped detection by IHC. Thus, IHC cannot be recommended to substitute MSA fully. Nonetheless, IHC is important to indicate the gene that is likely to be affected. To combine both methods efficiently, we propose a novel screening strategy that provides 2 alternative ways of sequential IHC and MSA application, either using IHC or MSA in the first place. A logistic regression model based on the age of the index patient at first tumor diagnosis and the number of fulfilled HNPCC criteria is used to allocate individual patients to that alternative pathway that is expected to be least expensive. A cost analysis reveals that about 25% of the costs can be saved using this strategy. (c) 2005 Wiley-Liss, Inc.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MISMATCH-REPAIR-GENE; MSH6 GERMLINE MUTATIONS; COLON-CANCER; BETHESDA GUIDELINES; EXPRESSION ANALYSIS; INSTABILITY; FAMILIES; HNPCC; HOMOLOG; MLH1; hereditary nonpolyposis colorectal cancer; Amsterdam criteria; Bethesda guidelines; immunohistochemistry; microsatellite analysis; mutation analysis; tumor screening; diagnostic strategy; cost analysis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Mar 2021 09:03 |
| Last Modified: | 02 Mar 2021 09:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/35181 |
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