Rapid increase in plasma tenascin‐C concentration after isolated limb perfusion with high‐dose tumor necrosis factor (TNF), interferon gamma (IFNγ) and melphalan for regionally advanced tumors

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Abstract
The matrix protein tenascin‐C (TN‐C) is present in the blood of healthy individuals at concentrations around 1 mg/1. Elevated serum levels have been reported in cancer patients. In this study we have measured the concentration of circulating TN‐C in 40 patients with melanoma, soft‐tissue sarcoma (STS) or squamous‐cell carcinoma (SCC) of the limbs, and have found a minor increase in the mean concentration compared with healthy subjects. Only 10 patients had TN‐C levels above the normal range. No correlation was observed between TN‐C levels and tumor burden. Nineteen patients were treated by isolation limb perfusion (ILP) with TNF, IFNγ, melphalan (11 melanoma, 2 SCC and 1 STS), melphalan alone (3 melanoma) or hyperthermia at 41.5°C (2 melanoma). ILP with TNF, IFNγ and melphalan induced a rapid increase in plasma TN‐C levels, peaking in most patients between 24 to 48 hr after ILP. Two patients treated with hyperthermia only had a slow increase in TN‐C concentration peaking at day 4, while the patients treated with melphalan alone had no significant change. In some cases elevated TN‐C levels persisted for over 8 weeks after ILP. The early rise in TN‐C concentration correlates with the increase in circulating C‐reactive protein. Our findings suggest that circulating TN‐C behaves, at least in part, as an acute‐phase protein and that it may play a role in the inflammatory response. © 1995 Wiley‐Liss, Inc.