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Value of detection of DNA mismatch repair proteins deficiency by immunohistochemistry in predicting tumor microsatellite status / 中华病理学杂志
Chinese Journal of Pathology ; (12): 704-708, 2015.
Article in Chinese | WPRIM | ID: wpr-359035
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the sensitivity and specificity of immunohistochemical (IHC) staining of DNA mismatch repair (MMR) protein for the screening of microsatellite instability (MSI) colorectal cancer (CRC).</p><p><b>METHODS</b>A total of 255 CRC cases were studied, including 140 cases of routine paraffin-embedded tissue samples and 115 cases constructed on tissue microarray. Expressions of 4 MMR proteins including MHL1, MSH2, MSH6 and PMS2 were investigated by IHC. Negative protein expression was defined as complete absence of nuclear staining within tumor cells in the presence of positively labeled internal non-neoplastic cells. Focal staining was defined as the presence of staining in < 5% of the tumor cells. CRCs showing negative staining for any MMR proteins were interpreted as MMR deficient tumors. PCR-genescan MSI analysis was performed in each case by a five marker panel including Bat26, Bat25, NR-21, NR-24 and MONO-27.</p><p><b>RESULTS</b>Among the 140 CRCs with routine formalin-fixed paraffin embedded tissue sections, concordance rate between IHC and PCR-genescan was 98.6% (138/140), the sensitivity and specificity of IHC in detecting MSI tumors were 94.9% (37/39) and 100.0% (101/101), respectively. The 2 disconcordant cases showed focal staining in at least one of the MMR proteins but were confirmed to be MSI-H CRCs by PCR-genescan assay. On tissue microarray, 91.3% (105/115) of the cases had informative results. The concordance rate between IHC and PCR-genescan was 100.0% (105/105). Both the specificity and sensitivity of IHC in detecting MSI tumors on available tissue microarray samples were 100.0%. Ten cases were inclusive due to the presence of negative stains of MMR proteins in both the tumor and internal control cells.</p><p><b>CONCLUSIONS</b>Detection of 4 MMR proteins expression by IHC is reliable for identifying MSI CRCs and is recommended for routine practice. Tumors with focal MMR protein staining are highly suspected for the presence of MSI-H and PCR-genescan based MSI analysis should be performed to confirm.</p>
Subject(s)
Full text: Available Index: WPRIM (Western Pacific) Main subject: Immunohistochemistry / Colorectal Neoplasms / Polymerase Chain Reaction / Sensitivity and Specificity / DNA-Binding Proteins / Microsatellite Instability / DNA Mismatch Repair / Genetics Type of study: Diagnostic study / Prognostic study Limits: Humans Language: Chinese Journal: Chinese Journal of Pathology Year: 2015 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Immunohistochemistry / Colorectal Neoplasms / Polymerase Chain Reaction / Sensitivity and Specificity / DNA-Binding Proteins / Microsatellite Instability / DNA Mismatch Repair / Genetics Type of study: Diagnostic study / Prognostic study Limits: Humans Language: Chinese Journal: Chinese Journal of Pathology Year: 2015 Type: Article