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From the Departments of Pathology,*
Microbiology and
Immunology,
and
Surgery,
University of Texas Medical Branch,
Galveston, Texas; and the Department of
Pathology,
University of Chicago Hospitals,
Chicago, Illinois
The histological diagnosis of hepatocellular carcinoma (HCC) can be
complicated by difficulty in differentiation from cholangiocarcinoma
and metastatic carcinoma. Immunohistochemical stains currently in use
are suboptimal in terms of specificity and sensitivity. Using cDNA
array analysis for differential gene expression, we
demonstrated a significant increase in mRNA expression level of
CD10/CALLA, a type 2 cell-surface metalloproteinase, in
HCC, which was subsequently confirmed by reverse
transcriptase-polymerase chain reaction and Western blotting analysis.
To test the possibility of using CD10/CALLA as a diagnostic marker for
HCC, various intrahepatic tumors were studied
immunohistochemically using a monoclonal antibody for CD10. A
characteristic canalicular-staining pattern was observed in normal
hepatocytes and at the apical surface of bile duct epithelial cells.
The canalicular expression of CD10 was identified in 9 of 15 HCCs
examined (60%), whereas 10 cholangiocarcinomas and 8 of 9
metastatic carcinomas lacked this staining. In three of the six HCCs
negative for CD10, the surrounding nonneoplastic liver tissue
was also negative, suggesting fixation-associated loss of
immunoreactivity. Six HCCs had stronger CD10 staining in tumor cells
when compared to the surrounding nonneoplastic tissue. Three cases of
benign bile duct adenomas also expressed CD10 at the luminal aspect.
One of the MCs showed a diffuse, cytoplasmic staining for
CD10, a pattern readily distinguishable from that of HCC. A
panel of other immunohistochemical markers were also studied for
comparison, including polyclonal anti-carcinoembryonic
antigen, cytokeratin (CK) 7, CK20, and
-fetoprotein. Our results demonstrate that cDNA arrays can be
effectively used to identify new diagnostic markers, and that
CD10 is a reliable marker for identifying HCC, particularly
when used in conjunction with a panel of immunohistochemical markers
(polyclonal anti-carcinoembryonic antigen, CK7,
CK20, and -fetoprotein) and in the distinction from
cholangiocarcinoma.
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