Tumour
necrosis factor-alpha (TNF) has been used in the clinic for more than 10 years in an isolated limb perfusion (ILP). However, intra-tumoural expression of TNF receptor-1 (TNF-R1) and TNF-R1 upregulating factors are unknown. We determined the expression of TNF-R1, proEMAP and
endothelial monocyte-activating polypeptide-II (
EMAP-II) before and after ILP and evaluated this against clinical response. Tumour biopsies were taken before and after ILP of patients (n = 27) with advanced
sarcoma or metastatic
melanoma. Biopsies were randomly analysed by western blotting for proEMAP/
EMAP-II and TNF-R1 expression. Appropriate
melanoma biopsies were stained for
EMAP-II, TNF-R1, CD31 and CD68. For
melanomas we found that an up-regulation of
EMAP-II, in contrast to proEMAP or TNF-R1, directly after ILP significantly correlated with a complete tumour response. No correlation was found for
sarcoma patients. In a comparative analysis we found that the overall proEMAP and
EMAP-II expression was higher in
melanoma as compared to
sarcoma cases and measurements in cell lines revealed high proEMAP expression by
melanoma cells. We report high
EMAP-II expression by endothelial cells and association with macrophages. In addition, macrophages are recruited to vessel-remnants after ILP. An upregulation of
EMAP-II directly after ILP of
melanoma patients correlates with and might predict a complete response to TNF-based ILP. The association of macrophages with
EMAP-II expression and vascular damage suggests a role for
EMAP-II in regulating the TNF-based anti-tumour effects observed with an ILP. Analysis of
EMAP-II expression in
melanoma biopsies should be implemented in the ILP procedure.