Unique histopathologic features of brain metastases from hepatocellular carcinoma.

Abstract

169 Background: In the era of anti-angiogenic therapy as treatment for advanced hepatocellular carcinoma (HCC), the incidence and importance of brain metastases are increasing. We aimed to study their histopathologic features. Methods: We searched for all patients who were diagnosed to have HCC with brain metastasis from 1999 to 2010 at National Taiwan University Hospital, Taipei, Taiwan. Patients who had HCC with lung metastasis were also included for comparison. Patients with available tissues of both primary and metastatic tumors were enrolled in this study. Tumor slides from paired primary and metastatic HCCs were stained by H and E, and immunohistochemically stained for CK7, p53, Ki67, vimentin, Hes1, and c-Met. The expressions of CK7, p53, and vimentin were graded according to percentages of positive staining, but those of Hes1 and c-Met were recorded as an H score, which was defined as intensity (0, 1, 2, or 3) × percentages of positive staining. Results: A total of 14 patients had available tumor tissues of both primary and metastatic brain tumors. Another 21 patients had tumor tissues of both primary and metastatic lung tumors. The metastatic brain tumors, comparing to the metastatic lung tumors, had significantly more bizarre dilated vessels (86% vs. 14%, p < 0.001), hyaline globules (50% vs. 5%, p = 0.003), higher Hes1 H scores (mean, 245 vs. 131, p = 0.001), and lower c-Met H scores (mean, 15.4 vs. 38.1, p = 0.046). Tumor necrosis also tended to be more common among metastatic brain tumors (93% vs. 62%, p = 0.056). On the contrary, the above differences were not identified between the primary tumors which later developed brain metastasis and those which later developed lung metastasis. When disease progressed from primary liver to brain metastasis, mitosis counts (p = 0.034) and bizarre dilated vessels (p = 0.020) significantly increased, and necrosis (p = 0.059) tended to be more common. Conclusions: Metastatic brain tumors from HCC had unique histopathologic features compared to primary liver tumors or lung metastases. The increased Hes1 expression and decreased c-Met expression in HCC brain metastasis should be further explored. (This study was supported by the grant of NSC101-2314-B-002 -141, 100CAP1020-2 & NTUH.101-N1965.)