Reduced expression of cytokeratin 20 in colorectal carcinomas with high levels of microsatellite instability

David K. McGregor, Tsung Teh Wu, Asif Rashid, Rajyalakshmi Luthra, Stanley R. Hamilton

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

High levels of microsatellite instability (MSI-H) result from abnormal nucleotide mismatch repair in a subset of sporadic colorectal carcinomas (CRC) and in most CRC of hereditary non-polyposis colorectal cancer syndrome. CRC with MSI-H have distinctive clinical-pathologic features, but the immunophenotype has not been studied extensively. We evaluated immunohistochemical expression of cytokeratin 7 (CK7), cytokeratin 20 (CK20), and pancytokeratin (panCK) in 44 CRC from 22 paired MSI-H and microsatellite-stable (MSS) cases matched for clinical-pathologic characteristics. The mean percentage of CK20+ tumor cells was 84 ± 6% in MSS CRC but only 37 ± 8% in MSI-H CRC (P = 0.0007). Thirty-two percent (7/22, 95% confidence interval 14-55%) of MSI-H CRC were CK20-, as contrasted with 9% (2/22, 95% CI 1-29%, P = 0.13) of MSS CRC. CK20 expression was inversely correlated with levels of MSI (rs = -0.45, P = 0.006). CK7+ was infrequent (16%, 7/44, 95% CI 7-30%) and panCK+ was universal, with no significant differences between MSI-H and MSS CRC. Our study shows that decreased or even absent CK20 expression is a phenotypic characteristic of MSI-H CRC and that MSI-H explains much of the subset of CRC that lack CK20 expression. Our results also indicate that regulation of CK20 gene expression involves molecular pathways that are altered by MSI-H.

Original languageEnglish (US)
Pages (from-to)712-718
Number of pages7
JournalAmerican Journal of Surgical Pathology
Volume28
Issue number6
DOIs
StatePublished - Jun 2004
Externally publishedYes

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Keratin-20
Microsatellite Instability
Colorectal Neoplasms
Microsatellite Repeats
Keratin-7
N-methylsuccinimide
DNA Mismatch Repair

Keywords

  • Colorectal carcinoma
  • Cytokeratin 20
  • Microsatellite instability
  • Pancytokeratin

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine

Cite this

Reduced expression of cytokeratin 20 in colorectal carcinomas with high levels of microsatellite instability. / McGregor, David K.; Wu, Tsung Teh; Rashid, Asif; Luthra, Rajyalakshmi; Hamilton, Stanley R.

In: American Journal of Surgical Pathology, Vol. 28, No. 6, 06.2004, p. 712-718.

Research output: Contribution to journalArticle

McGregor, David K. ; Wu, Tsung Teh ; Rashid, Asif ; Luthra, Rajyalakshmi ; Hamilton, Stanley R. / Reduced expression of cytokeratin 20 in colorectal carcinomas with high levels of microsatellite instability. In: American Journal of Surgical Pathology. 2004 ; Vol. 28, No. 6. pp. 712-718.
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abstract = "High levels of microsatellite instability (MSI-H) result from abnormal nucleotide mismatch repair in a subset of sporadic colorectal carcinomas (CRC) and in most CRC of hereditary non-polyposis colorectal cancer syndrome. CRC with MSI-H have distinctive clinical-pathologic features, but the immunophenotype has not been studied extensively. We evaluated immunohistochemical expression of cytokeratin 7 (CK7), cytokeratin 20 (CK20), and pancytokeratin (panCK) in 44 CRC from 22 paired MSI-H and microsatellite-stable (MSS) cases matched for clinical-pathologic characteristics. The mean percentage of CK20+ tumor cells was 84 ± 6{\%} in MSS CRC but only 37 ± 8{\%} in MSI-H CRC (P = 0.0007). Thirty-two percent (7/22, 95{\%} confidence interval 14-55{\%}) of MSI-H CRC were CK20-, as contrasted with 9{\%} (2/22, 95{\%} CI 1-29{\%}, P = 0.13) of MSS CRC. CK20 expression was inversely correlated with levels of MSI (rs = -0.45, P = 0.006). CK7+ was infrequent (16{\%}, 7/44, 95{\%} CI 7-30{\%}) and panCK+ was universal, with no significant differences between MSI-H and MSS CRC. Our study shows that decreased or even absent CK20 expression is a phenotypic characteristic of MSI-H CRC and that MSI-H explains much of the subset of CRC that lack CK20 expression. Our results also indicate that regulation of CK20 gene expression involves molecular pathways that are altered by MSI-H.",
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