Deficient DNA mismatch repair is common in Lynch syndrome-associated colorectal adenomas

Maria Simona Pino, Mari Mino-Kenudson, Bernadette Mandes Wildemore, Aniruddha Ganguly, Julie Batten, Isabella Sperduti, Anthony John Iafrate, Daniel C. Chung

Research output: Contribution to journalArticle

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Abstract

Lynch syndrome is caused by germline mutations in DNA mismatch repair (MMR) genes. Both microsatellite instability (MSI) testing and immunohistochemical analyses (IHC) of colon cancers are valuable diagnostic strategies for Lynch syndrome. We sought to determine whether these markers of MMR deficiency were also detectable in pre-cancerous colorectal adenomas. Fifteen subjects with a germline MMR gene mutation who had 44 adenomas removed during surveillance colonoscopy were identified. MSI testing and IHC for MLH1, MSH2, and MSH6 were performed. MSI was detected in 23 adenomas. There was a significant association between MSI and high-grade dysplasia (P = 0.006) and distal location (P = 0.0008). Loss of MMR protein by IHC was detected in 31 adenomas. A significant association was observed between loss of staining by IHC and high-grade dysplasia (P = 0.04). Among the 40 adenomas in which both MSI tests and IHC were performed, the presence of a germline mutation correlated with an abnormal MSI result in 58% of cases, an abnormal IHC result in 70% of cases, and either an abnormal MSI or IHC result in 73% of cases. The combination of MSI and IHC testing in colorectal adenomas is a sensitive screen for the detection of Lynch syndrome and may be particularly useful when Lynch syndrome is suspected and adenomatous polyps are the only tissues available for analysis.

Original languageEnglish
Pages (from-to)238-247
Number of pages10
JournalJournal of Molecular Diagnostics
Volume11
Issue number3
DOIs
Publication statusPublished - May 2009

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DNA Repair-Deficiency Disorders
Hereditary Nonpolyposis Colorectal Neoplasms
Microsatellite Instability
DNA Mismatch Repair
Adenoma
Germ-Line Mutation
Adenomatous Polyps
Colonoscopy
Colonic Neoplasms
Genes
Staining and Labeling
Mutation

ASJC Scopus subject areas

  • Molecular Medicine
  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

Pino, M. S., Mino-Kenudson, M., Wildemore, B. M., Ganguly, A., Batten, J., Sperduti, I., ... Chung, D. C. (2009). Deficient DNA mismatch repair is common in Lynch syndrome-associated colorectal adenomas. Journal of Molecular Diagnostics, 11(3), 238-247. https://doi.org/10.2353/jmoldx.2009.080142

Deficient DNA mismatch repair is common in Lynch syndrome-associated colorectal adenomas. / Pino, Maria Simona; Mino-Kenudson, Mari; Wildemore, Bernadette Mandes; Ganguly, Aniruddha; Batten, Julie; Sperduti, Isabella; Iafrate, Anthony John; Chung, Daniel C.

In: Journal of Molecular Diagnostics, Vol. 11, No. 3, 05.2009, p. 238-247.

Research output: Contribution to journalArticle

Pino, MS, Mino-Kenudson, M, Wildemore, BM, Ganguly, A, Batten, J, Sperduti, I, Iafrate, AJ & Chung, DC 2009, 'Deficient DNA mismatch repair is common in Lynch syndrome-associated colorectal adenomas', Journal of Molecular Diagnostics, vol. 11, no. 3, pp. 238-247. https://doi.org/10.2353/jmoldx.2009.080142
Pino, Maria Simona ; Mino-Kenudson, Mari ; Wildemore, Bernadette Mandes ; Ganguly, Aniruddha ; Batten, Julie ; Sperduti, Isabella ; Iafrate, Anthony John ; Chung, Daniel C. / Deficient DNA mismatch repair is common in Lynch syndrome-associated colorectal adenomas. In: Journal of Molecular Diagnostics. 2009 ; Vol. 11, No. 3. pp. 238-247.
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