Gross appearance of hepatocellular carcinoma reflects E‐cadherin expression and risk of early recurrence after surgical treatment

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Abstract
Background and Aims: Correlation between the gross classification of hepatocellular carcinoma (HCC) and its vascular invasion or intrahepatic metastasis has been reported previously. Because E‐cadherin‐mediated epithelial cell‐to‐cell adhesion is thought to suppress cancer cell invasion, the present study was performed to analyze the correlation between E‐cadherin expression and the gross classification of HCC. Methods: Thirty‐six resected solitary HCC <6 cm in diameter were each classified as single nodular type (type 1), single nodular with extranodular growth type (type 2) or contiguous multinodular type (type 3), and the clinicopathological and prognostic differences between type 1 HCC and the other types were analyzed. The expression of E‐cadherin in each tumor was examined by immunoblotting and immunohistochemical analysis. Results: Vascular invasion and microscopic intrahepatic metastasis were observed more frequently in types 2 and 3 (61%) than in type 1 (13%) HCC. Immunoblot analysis indicated that the relative level of E‐cadherin expression in cancerous tissue was significantly lower in type 2 and 3 (0.75 ± 0.49) than in type 1 (1.46 ± 0.79) HCC. Immunohistochemical examination revealed decreased and partially absent E‐cadherin expression in the tumorous area of type 2 and 3 HCC. The recurrence‐free survival rate was higher for patients with type 1 HCC than for those with the other types. Conclusions: Types 2 and 3 HCC have marked metastatic and invasive potential and reduced expression of E‐cadherin, predicting a high risk of recurrence after surgical treatment.