Transcription factor ERG is a specific and sensitive diagnostic marker for hepatic angiosarcoma

Aim: To investigate the expression of ERG, CD34, CD31 (PECAM-1, platelet/endothelial cell adhesion molecule 1) and factor VIII-related antigen (FVIIIRAg) in the diagnosis of hepatic angiosarcoma patients.

Methods: Patient samples were collected from January 1986 to December 2012 from the People's Liberation Army General Hospital in Beijing, China. We obtained twenty-four samples of hepatic angiosarcoma (HAS) that were confirmed by two pathologist. The samples were the result of three autopsy cases, eight biopsy cases and 13 patients who underwent surgical tumor removal. The HAS cases accounted for 2.23% (24/1075) of all hepatic vascular tumors at the hospital during the same time period. Patient histories including age, gender, clinical manifestations, medical treatments, laboratory tests, radiological images, histological observations and outcomes for each case were analyzed in detail. All samples were evaluated histologically with hematoxylin and eosin staining. Using immunohistochemistry, the expression and localization of ERG was examined in all HAS specimens and compared to the known endothelial markers CD34, CD31 and FVIIIRAg. The endothelial markers were also evaluated in a panel of non-HAS tumors.

Results: This cohort of 24 HAS cases is, to the best of our knowledge, currently the largest cohort in the world in the publicly available literature. Hepatic angiosarcoma tissue samples were obtained from 14 males and 10 females with a mean age of 50.6 years (range: 7-86 years). The patients presented with the following clinical manifestations: abdominal pain (16/24), back pain (3/24), heart palpitations (1/20), cough (1/24) or no clinical symptoms (3/24). Tumors were predominantly localized in the right hepatic lobe (15/24) or left hepatic lobe (6/24), or a diffuse growth on the right and left hepatic lobes (3/24). Eleven patients underwent surgical resection (45.8%), two patients received a liver transplant (8.3%), eight patients received interventional therapy (33.3%) and three patients received no treatment (lesions discovered at autopsy, 12.5%). Postoperative follow-up of patients revealed that 87.5% (21/24) of patients had died and three cases were not able to be tracked. In all cases, the mean survival time was 12.1 mo. While 100% of the HAS samples were positive for ERG expression, expression of the other markers was more variable. CD31 was expressed in 79.2% (19/24) of samples, CD34 was expressed in 87.5% (21/24) of samples and FVIIIRAg was expressed in 41.7% (10/24) of samples.

Conclusion: ERG is a more sensitive and specific diagnostic marker for hepatic angiosarcoma in comparison to CD31, CD34 and FVIIIRAg.

Angiosarcoma; Diagnosis; ERG; Immunohistochemistry; Liver.