Reduced expression of cytokeratin 20 in colorectal carcinomas with high levels of microsatellite instability.
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.
McGregor
David K
DK
Departments of Pathology and Hematopathology, Division of Pathology and Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Wu
Tsung-Teh
TT
Rashid
Asif
A
Luthra
Rajyalakshmi
R
Hamilton
Stanley R
SR
D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000235:genetics*; D005260:Female; D042822:Genomic Instability; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000032:analysis*; D053554:Keratin-20; D053552:Keratin-7; D007633:Keratins / Q000032:analysis; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies
D007381:Intermediate Filament Proteins; C507499:KRT20 protein, human; C507497:KRT7 protein, human; D053554:Keratin-20; D053552:Keratin-7; D007633:Keratins