Utility of p16 Immunohistochemistry for the Identification of Lynch Syndrome
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Title: | Utility of p16 Immunohistochemistry for the Identification of Lynch Syndrome |
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Authors: | Payá, Artemio | Alenda, Cristina | Pérez-Carbonell, Lucía | Rojas, Estefanía | Soto, José Luis | Guillén-Ponce, Carmen | Castillejo, Adela | Barberá, Víctor Manuel | Carrato, Alfredo | Castells, Antoni | Llor, Xavier | Andreu, Montserrat | Koh, Jim | Enders, Greg H. | Benlloch, Susana | Jover, Rodrigo |
Research Group/s: | Transducción de Señales en Bacterias |
Center, Department or Service: | Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología |
Keywords: | Immunohistochemistry | p16 | Lynch Syndrome |
Knowledge Area: | Genética |
Issue Date: | 1-May-2009 |
Publisher: | American Association for Cancer Research |
Citation: | PAYÁ, Artemio, et al. "Utility of p16 Immunohistochemistry for the Identification of Lynch Syndrome". Clinical Cancer Research. Vol. 15, No. 9 (May 2009). ISSN 1078-0432, pp. 3156-3162 |
Abstract: | Purpose: Immunohistochemistry for mismatch repair proteins has shown utility in the identification of Lynch syndrome, but majority of tumors with loss of MLH1 expression are due to sporadic hypermethylation of the MLH1 promoter. These tumors can also show epigenetic silencing of other genes, such as p16. The aim of our study is to evaluate the utility of p16 immunohistochemistry in the prediction of MLH1germline mutations. Experimental Design: p16 immunohistochemistry was appropriately evaluated in 79 colorectal cancers with loss ofMLH1expression.Methylation of MLH1 and p16 were quantitatively studied using real-time PCR assay Methylight. BRAF V600E mutation in tumor tissue was also investigated. Genetic testing for germline mutation of MLH1was made on 52 patients. Results: Loss of p16 expression was seen in 21 of 79 samples (26.6%). There was found statistically significant association between p16 expression and p16 methylation (P < 0.001), MLH1 methylation (P < 0.001), and BRAF mutation (P < 0.005). All tumors with loss of p16 expression showed hypermethylation of p16 (21of 21), 95.2% (20 of 21) showed MLH1 methylation, and 71.4% (15 of 21) were mutated for BRAF V600E. Mutational analysis showed pathogenic germline mutations in 8 of the patients, harboring 10 tumors. All 10 of these tumors showed normal staining of p16 in the immunochemical analysis. Conclusions: p16 immunohistochemistry is a good surrogate marker for p16 and MLH1 epigenetic silencing due to hypermethylation, and is useful as screening tool in the selection of patients for genetic testing in Lynch syndrome. |
Sponsor: | Generalitat Valenciana Conselleria de Sanitat (AP 021/07), Fundación de la CV para la Investigación en el Hospital General Universitario de Alicante (2008). Beca predoctoral Instituto de Salud Carlos III (FI07/00303, Lucía Perez-Carbonell). |
URI: | http://hdl.handle.net/10045/20242 |
ISSN: | 1078-0432 (Print) | 1557-3265 (Online) |
DOI: | 10.1158/1078-0432.CCR-08-3116 |
Language: | eng |
Type: | info:eu-repo/semantics/article |
Rights: | Copyright © 2009 American Association for Cancer Research |
Peer Review: | si |
Publisher version: | http://dx.doi.org/10.1158/1078-0432.CCR-08-3116 |
Appears in Collections: | INV - TSB - Artículos de Revistas INV - GIDBT - Artículos de Revistas |
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File | Description | Size | Format | |
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Clinical Cancer Research 2009.pdf | Versión final (acceso restringido) | 352,33 kB | Adobe PDF | Open Request a copy |
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