Immunohistochemical staining of cancer stem cell markers in hepatocellular carcinoma.
BACKGROUND
Cancer stem cells (CSCs) are thought to be a critical subpopulation in tumor development, progression, metastasis and recurrence, and the identification of these cells is an initial step in understanding their role in oncogenesis and in seeking valuable markers for diagnosis or development of targeting therapeutics.


OBJECTIVE
To identify CSCs in hepatocellular carcinoma (HCC) specimens and define their tissue specificity.


METHODS
Immunohistochemical staining of CSC markers: CD44, CD90, CD133 and aldehyde dehydrogenase (ALDH) was performed in 25 HCC specimens, 4 hepatoblastomas, 8 peri-malignant tissues, and 19 cases of viral hepatitis.


RESULTS
The positivity of CD44 staining in HCC specimens was significantly lower than in viral hepatitis specimens. The positive rate of CD133 in HCC was similar to viral hepatitis specimens. CD133(+) cells were largely localized to ALDH-positive cells in HCC as revealed by confocal microscopy. In contrast, the co-expression of both markers was visualized within vessels or in the portal areas in viral hepatitis. Moreover, among 7 liver specimens adjacent to HCC tissue, 3-6 samples were positive for CD44, CD90, CD133 and ALDH, especially in dysplastic cells. One of 4 hepatoblastoma cases was positive for all these markers; whereas, the other three specimens were negative for all these CSC markers.


CONCLUSIONS
In HCC and dysplastic tissues, clusters of CD133(+)/ALDH(high) cells were identified. The use of cancer stem cell markers to screen tissues with chronic liver diseases provides limited guidance in the identification of malignant cells.
Department of Internal Medicine, Division of Gastroenterology & Hepatology, University of California, Davis Medical Center, Sacramento, CA 95817, USA.
Shilpa
S
Lingala
Yi-Yao
YY
Cui
Xiaoli
X
Chen
Boris H
BH
Ruebner
Xiao-Feng
XF
Qian
Mark A
MA
Zern
Jian
J
Wu
D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006525:Hepatitis, Viral, Human / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000378:metabolism; D018800:Thy-1 Antigens / Q000378:metabolism; D055815:Young Adult
D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D006023:Glycoproteins; D018960:Hyaluronan Receptors; C000606023:PROM1 protein, human; D010455:Peptides; D018800:Thy-1 Antigens; D000444:Aldehyde Dehydrogenase