Automated, multiplex assay for high-frequency microsatellite instability in colorectal cancer Journal Article


Authors: Nash, G. M.; Gimbel, M.; Shia, J.; Culliford, A. T.; Nathanson, D. R.; Ndubuisi, M.; Yamaguchi, Y.; Zeng, Z. S.; Barany, F.; Paty, P. B.
Article Title: Automated, multiplex assay for high-frequency microsatellite instability in colorectal cancer
Abstract: Purpose: In a series of hereditary nonpolyposis colorectal cancer (HNPCC) patients, we evaluated the sensitivities of the individual microsatellites recommended by the National Cancer Institute (NCI) consensus workshop for detection of high-frequency microsatellite instability (MSI-H). On the basis of this evaluation, we developed a three-marker assay that assigns microsatellite instability (MSI) in a multiplex polymerase chain reaction. Methods: Individual marker sensitivity was assessed in 18 HNPCC tumors. Multiplex and NCI assays were then assessed in a series of 120 patients with early-onset colon cancer. Results: The sensitivity of microsatellite markers BAT25, BAT26, D2S123, D5S346, and D17S250 for ASI in HNPCC cancers was 100%, 94%, 72%, 50%, and 50%, respectively. The three most accurate markers were combined and optimized in a multiplex assay that assigned MSI-H whenever at least two of three markers revealed ASI. In early-onset colon cancers, the prevalence of MSI-H determined by the multiplex assay and by the NCI assay was 16% and 23%, respectively. The additional MSI-H tumors and patients with MSI-H identified by the NCI assay lacked the traits characteristic of MSI-H seen in tumors and patients identified by the multiplex assay: retention of heterozygosity (NCI additional 22% v multiplex 84%; P = .003), characteristic tumor morphology (0% v 64%; P = .006), and 5-year cancer survival rate (44% v 100%; P = .0003). Conclusion: The multiplex assay identifies colon cancers with MSI-H by assessing three highly accurate microsatellite markers. This assay identifies a smaller MSI-H cohort with more homogeneous clinical features and is superior as a marker of favorable prognosis. It merits prospective evaluation as a marker of prognosis and as a screening test for HNPCC. © 2003 by American Society of Clinical Oncology.
Keywords: controlled study; disease-free survival; middle aged; major clinical study; genetics; disease free survival; methodology; diagnostic accuracy; polymerase chain reaction; colorectal cancer; adenocarcinoma; prevalence; cancer screening; microsatellite dna; colorectal neoplasms; chromosome aberration; evaluation; early cancer; heterozygosity; colorectal tumor; microsatellite instability; nucleotide sequence; microsatellite marker; dna mutational analysis; chromosome aberrations; microsatellite repeats; multiplex polymerase chain reaction; humans; prognosis; human; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 21
Issue: 16
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2003-08-15
Start Page: 3105
End Page: 3112
Language: English
DOI: 10.1200/jco.2003.11.133
PUBMED: 12915601
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
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MSK Authors
  1. Mark I Gimbel
    14 Gimbel
  2. Philip B Paty
    500 Paty
  3. Zhaoshi Zeng
    87 Zeng
  4. Jinru Shia
    720 Shia
  5. Garrett Nash
    264 Nash