Original ArticleReduced Expression of Cytokeratin 20 in Colorectal Carcinomas With High Levels of Microsatellite InstabilityMcGregor, David K MD; Wu, Tsung-Teh MD, PHD; Rashid, Asif MD, PHD; Luthra, Rajyalakshmi PHD; Hamilton, Stanley R MDAuthor Information From the Departments of Pathology and Hematopathology, Division of Pathology and Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX. Reprints: Stanley R. Hamilton, MD, Division of Pathology and Laboratory Medicine, Unit 085, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030 (e-mail: firstname.lastname@example.org). The American Journal of Surgical Pathology: June 2004 - Volume 28 - Issue 6 - p 712-718 doi: 10.1097/01.pas.0000126757.58474.12 Buy SDC Metrics 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. © 2004 Lippincott Williams & Wilkins, Inc.