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Differences in Microsatellite Instability Profiles between Endometrioid and Colorectal Cancers: A Potential Cause for False-Negative Results?

Publication ,  Journal Article
Wang, Y; Shi, C; Eisenberg, R; Vnencak-Jones, CL
Published in: J Mol Diagn
January 2017

Colorectal (CRCs) and endometrioid (EMCs) cancers in patients with Lynch syndrome exhibit microsatellite instability (MSI) detected by PCR or immunohistochemistry (IHC). While both assays are equally sensitive for CRCs, some suggest that PCR has a higher false-negative rate than IHC in EMCs. We assessed the MSI profiles of 91 EMC and 311 CRC specimens using five mononucleotide repeat markers: BAT25, BAT26, NR21, NR24, and MONO27. EMCs with high MSI (MSI-H) showed a mean left shift of 3 nucleotides (nt), which was significantly different from 6 nt in CRCs. A shift of 1 nt was observed in multiple markers in 76% of MSI-H EMCs, whereas only 12% of MSI-H CRCs displayed a 1-nt shift in one of five markers. IHC against four mismatch repair proteins was performed in 78 EMCs. Loss of staining in one or more proteins was detected in 18 of 19 tumors that were MSI-H by PCR. When EMC tumor cell burden was diluted to <30%, MSI-H was no longer observed in two of three EMCs with a mean nucleotide shift of 1 nt. These results indicate that EMC and CRC MSI profiles are different and that caution should be exercised when interpreting the results, as subtle, 1-nt changes may be missed. These findings provide a potential cause of previously reported discordant MSI and IHC results in EMCs.

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Published In

J Mol Diagn

DOI

EISSN

1943-7811

Publication Date

January 2017

Volume

19

Issue

1

Start / End Page

57 / 64

Location

United States

Related Subject Headings

  • Young Adult
  • Retrospective Studies
  • Pathology
  • MutS DNA Mismatch-Binding Protein
  • Middle Aged
  • Microsatellite Repeats
  • Microsatellite Instability
  • Male
  • Humans
  • Female
 

Citation

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ICMJE
MLA
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Wang, Y., Shi, C., Eisenberg, R., & Vnencak-Jones, C. L. (2017). Differences in Microsatellite Instability Profiles between Endometrioid and Colorectal Cancers: A Potential Cause for False-Negative Results? J Mol Diagn, 19(1), 57–64. https://doi.org/10.1016/j.jmoldx.2016.07.008
Wang, Yang, Chanjuan Shi, Rosana Eisenberg, and Cindy L. Vnencak-Jones. “Differences in Microsatellite Instability Profiles between Endometrioid and Colorectal Cancers: A Potential Cause for False-Negative Results?J Mol Diagn 19, no. 1 (January 2017): 57–64. https://doi.org/10.1016/j.jmoldx.2016.07.008.
Wang, Yang, et al. “Differences in Microsatellite Instability Profiles between Endometrioid and Colorectal Cancers: A Potential Cause for False-Negative Results?J Mol Diagn, vol. 19, no. 1, Jan. 2017, pp. 57–64. Pubmed, doi:10.1016/j.jmoldx.2016.07.008.
Journal cover image

Published In

J Mol Diagn

DOI

EISSN

1943-7811

Publication Date

January 2017

Volume

19

Issue

1

Start / End Page

57 / 64

Location

United States

Related Subject Headings

  • Young Adult
  • Retrospective Studies
  • Pathology
  • MutS DNA Mismatch-Binding Protein
  • Middle Aged
  • Microsatellite Repeats
  • Microsatellite Instability
  • Male
  • Humans
  • Female