VEGF-C Expression in Advanced and Metastatic Hepatocellular Carcinoma (HCC): An Autopsy Study in Cirrhotic Patients.
Aloisio Felipe-Silva, Adhemar Longatto-Filho, Alda Wakamatsu, Clarissa Cassol, Venancio Alves. School Of Medicine, University of Sao Paulo, Brazil
Background: Vascular endothelial growth factor-C (VEGF-C) immune-expression in HCC has been related to poor prognosis, tumor progression, vascular invasion and lymph node metastases. VEGF-C may be a target for anti-angiogenic therapy for HCC.
Design: This retrospective transversal study of autopsied cirrhotic patients with HCC correlates VEGF-C immune-expression to the following clinicopathological variables: gender, age, viral hepatitis, alcoholism, number and size of tumors, histological grade and pattern, extrahepatic metastases (EHM) and large venous invasion (LVI). Samples from 42 patients were cored in a tissue microarray paraffin block. Immunohistochemistry was performed using anti-VEGF-C rabbit antibody (cod182255, Invitrogen, 1:200), amplified by short peroxidase-polymer system (Novolink, Novocastra). VEGF-C immune-expression was estimated in intensity (0-3+) and distribution of HCC cells staining (0-100%). A score from 0 (no staining) to 300 (100% strong staining) was assigned. Scores were considered strongly positive (≥200), moderately positive (100 to 199), weakly positive (<100) and negative. Statistical significance was examined with Fisher's exact P-test and Student's t-test.
Results: Median age was 58 years (M:F rate 3.6:1). Viral hepatitis and alcoholism were present in 74% and 33% of cases. A single liver tumor was detected in 40.5%. The largest tumor measured up to 2cm in 26%. Low grade (1-2) and high grade (3-4) tumors were 31% and 69%. EHM were detected in 12% (7.1% to lung, 4.8% to lymph node and 2.4% to small bowel). LVI was detected in 7.1%. VEGF-C staining was strong, moderate, weak and negative in 21.4%, 47.6%, 14.3% and 16.7% of intrahepatic HCC. Strong staining was associated with high grade tumors (p=0.04) and trended to be associated with larger tumor size (p=0.06). Strong staining was observed in 83.3% of EHM (p<0.01) and 33.3% of LVI (p=0.14). Strong staining was observed in 3/3 lung, 1/2 lymph node and 1/1 small bowel metastases. Moderate and strong staining in intrahepatic HCC were associated with the finding of EHM (p=0.04). EHM and LVI had higher staining scores than intrahepatic tumors (p=0.02). HCC with EHM had higher staining scores than tumors without EHM (p=0.02). Correlations with number of tumors and other clinicopathological data were not significant.
Conclusions: In this autopsy series, higher VEGF-C expression scores were observed in high grade tumors, tumors that have metastasized and in EHM, particularly to the lung, thus suggesting VEGF-C as a potential surrogate marker for hematogenous spread.
Category: Liver & Pancreas
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 253, Tuesday Morning