Aberrant expression of cytokeratin 7 as a histological marker of progression in primary biliary cirrhosis.
OBJECTIVE
We evaluated the aberrant expression of cytokeratin 7 (CK-7) in hepatocytes as a marker of cholestasis and progression in primary biliary cirrhosis (PBC).


METHODS
The expression of CK-7 was studied by immunohistochemistry in 83 cases of PBC. This expression was compared with biochemical data, the deposition of copper-associated protein, and previous histological classifications.


RESULTS
In normal liver, CK-7 was expressed exclusively in bile duct epithelial cells (BDE). In PBC, the expression was also observed in hepatocytes. The expression pattern was classified as follows: Grade 0, BDE as in normal; Grade 1, proliferated bile ductules; Grade 2, periportal hepatocytes in addition to proliferated bile ductules; Grade 3, intralobular hepatocytes; Grade 4, the majority of hepatocytes. The grades correlated with serum bilirubin levels but not with serum levels of biliary enzymes. A discrepancy between the CK-7 grading and Ludwig's classification was noted in cases with Stage 1 of the CK-7 grading who were considered Stage 2 or 3 in Ludwig's classification, suggesting that cholestasis and inflammatory activity might be independent events.


CONCLUSIONS
These results suggest that the aberrant expression of CK-7 in hepatocytes may be a marker of chronic cholestasis and progression in PBC.
Yabushita
K
K
First Department of Internal Medicine, Okayama University Medical School, Japan.
Yamamoto
K
K
Ibuki
N
N
Okano
N
N
Matsumura
S
S
Okamoto
R
R
Shimada
N
N
Tsuji
T
T
D000469:Alkaline Phosphatase / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000276:immunology; D001646:Bile / Q000201:enzymology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers; D001706:Biopsy; D002780:Cholestasis, Intrahepatic / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D019085:Fluorescent Antibody Technique, Direct; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053552:Keratin-7; D007633:Keratins / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000175:diagnosis* / Q000378:metabolism; D015203:Reproducibility of Results; D005723:gamma-Glutamyltransferase / Q000032:analysis
D000911:Antibodies, Monoclonal; D015415:Biomarkers; C507497:KRT7 protein, human; D053552:Keratin-7; D007633:Keratins; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase; D001663:Bilirubin