Microscopic vascular invasion detected by anti-CD34 immunohistochemistry as a predictor of recurrence of hepatocellular carcinoma after liver transplantation

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Abstract
Background. Vascular invasion (VI) is the strongest risk factor for recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT). However, unlike macroscopic VI, microscopic VI has not been acknowledged as a predictor of recurrence in individual patients. This study aimed to determine whether immunohistochemical staining of the vessels could change the judgment on microscopic VI in such a way as to confer clinical relevance to the feature. Methods. Antibodies against the CD34 antigen (endothelial cell marker of hepatocarcinogenesis) were applied to sections from all the HCC nodules found in 136 patients who underwent LT for HCC arising from cirrhosis between 1990 and 2000. Microscopic VI at the periphery of the nodules was searched blindly by the same pathologist who had already examined hematoxylin-eosin slides. Several characteristics of the patients and of the cancers were analyzed to define their respective influence on recurrence. Results. Recurrent HCC was diagnosed in nine patients. Although 6 of the 22 patients in whom microscopic VI had been detected by hematoxylin-eosin staining developed recurrence, 8 of the 16 in whom microscopic VI was detected by anti-CD34 immunohistochemistry developed recurrence, accounting for 5-year cumulative incidences of recurrence of 34% and 70%, respectively. At multivariate analysis, relative risk for recurrence was the highest for microscopic VI found with anti-CD34 antibodies. Conclusions. Microscopic VI detected by anti-CD34 immunohistochemistry implies an extremely high risk for HCC to recur after LT. Trials focusing on patients with evidence of microscopic VI are needed to test the efficacy of adjuvant therapies to prevent recurrence.