The Sialyl Lewis X expression in hepatocarcinogenesis: potential predictor for the emergence of hepatocellular carcinoma.
OBJECTIVE
Sialyl Lewis X (sLeX), one of the cancer-associated glycoproteins, has been reported to be expressed in both liver tissue from various types of liver disease and hepatocellular carcinoma. In order to clarify sLeX expression during the early stage of hepatocarcinogenesis, we examined sLeX expressions in either liver tissue specimens without any nodular lesions, dysplastic nodules or hepatocellular carcinomas.


METHODS
Immunohistochemical observations were performed using a monoclonal antibody for sLeX. As for the liver tissue specimens, 8 livers without any chronic liver disease and 42 diseased livers were examined, while for the nodular lesions, 5 dysplastic nodules (borderline lesions) and 47 hepatocellular carcinomas were examined in this study.


RESULTS
sLeX was not expressed in all 8 normal livers. sLeX was expressed membraneously in 8 of 15 (53%) chronic hepatitic liver tissue specimens, in 8 of 9 (89%) precirrhotic liver tissue specimens and in 16 of 18 (89%) cirrhotic liver tissue specimens. The incidence of sLeX expression on hepatocytes in both pre-cirrhotic and cirrhotic liver tissue was higher than that in chronic hepatitic liver tissue (P < 0.05). The sLeX expression in liver tissue was positive in all 14 liver tissue specimens containing multiple hepatocellular carcinomas, in which at least one of the nodules was a well-differentiated hepatocellular carcinoma regarded as multicentric hepatocellular carcinomas. In 18 of 28 (64%) liver tissue specimens without multicentric hepatocellular carcinomas, sLeX was positive and the difference was statistically significant (P < 0.05). In nodular lesions, sLeX was negative in 5 dysplastic nodules (borderline lesions). In hepatocellular carcinoma, 14 of 47 (30%) hepatocellular carcinoma nodules showed a positive expression. Six of 14 (43%) well-differentiated hepatocellular carcinomas were positive on the cell membrane. Four of 23 (17%) moderately differentiated hepatocellular carcinomas were positive on the cell membrane, while one of 23 (4%) moderately differentiated hepatocellular carcinoma was positive in the cytoplasm. In addition, 3 of 10 (30%) poorly differentiated hepatocellular carcinomas were positive in the cytoplasm.


CONCLUSIONS
These results suggested that the sLeX-positive liver tissue specimens possessed a high degree of carcinogenicity and therefore sLeX expression in the diseased liver might be a good predictor for hepatocellular carcinoma emergence. At the same time, the suppression of sLeX occurred at a very early stage of hepatocarcinogenesis. In addition, the phenotype of sLeX was also considered to change during the progression of hepatocarcinogenesis.
Fujiwara
Yuh
Y
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Shimada
Mitsuo
M
Takenaka
Kenji
K
Kajiyama
Kiyoshi
K
Shirabe
Ken
K
Sugimachi
Keizo
K
D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002908:Chronic Disease; D006801:Humans; D007150:Immunohistochemistry; D016256:Lewis X Antigen / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D009844:Oligosaccharides / Q000378:metabolism*; D011237:Predictive Value of Tests; D000080506:Sialyl Lewis X Antigen
D016256:Lewis X Antigen; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen