Home Neoplasma 2004 Neoplasma Vol.51, p.275-284, 2004

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ISSN 0028-2685
ISSN 1338-4317 (online)

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Neoplasma Vol.51, p.275-284, 2004

Title: Immunohistochemical detection of the hMLH1 and hMSH2 proteins in hereditary non-polyposis colon cancer and sporadic colon cancer
Author: P., PLEVOVA ; A., KREPELOVA ; M., PAPEZOVA ; E., SEDLAKOVA ; R., CURIK ; L., FORETOVA ; M., NAVRATILOVA ; J., NOVOTNY ; J., ZAPLETALOVA ; J., PALAS ; J., NIESLANIK ; J., HORACEK

Abstract: We analyzed 81 samples (74 colon cancers (CC), 1 colon dysplasia and 6 extracolonic cancers) for hMLH1 and hMSH2 protein expression, microsatellite instability (MSI) and/or mutational analysis. A metaanalysis of the published data on immunohistochemistry of hMLH1/hMSH2 proteins was performed. Sensitivity and specificity of the method was calculated. Twenty four of 29 tumors from hMLH1/hMSH2 mutation carriers and 10 of 13 sporadic high frequency MSI tumors lost one of the proteins. None of the 42 tumors with stable microsatellites or low frequency MSI lost the proteins. Based on literature review of 49 publications on colorectal cancer, hMLH1 immunohistochemistry was able to detect 136 of 154 tumors from hMLH1 germline mutation carriers (the sensitivity of 88.3% [95%CI, 85.8--90.8%]), hMSH2 immunohistochemistry detected 99 of 109 tumors from hMSH2 mutation carriers (the sensitivity of 90.8% [95%CI, 88.5--93.1%]), and hMLH1/hMSH2 immunohistochemistry identified 1262 of 1382 tumors with high-frequency microsatellite instability not correlated with mutational analysis (the sensitivity of 91.3% [95%CI, 90.4--92.2%]). The specificity of the method was 99.4% (95%CI, 99.2--99.6%). In conclusion, immunohistochemistry of hMLH1 and hMSH2 proteins is a useful method to predict the presence of mismatch repair deficiency, although its sensitivity is lower than that of MSI analysis.

Keywords: hereditary nonpolyposis, hMLH1 gene -- mutations, hMSH2 gene -- mutations, hMLH1/hMSH2 protein -- detection, microsatellite instability
Year: 2004, Volume: 51, Issue: Page From: 275, Page To: 284

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