Posters— Medical Oncology

EXPRESSION OF FAS LIGAND AND FAS IN HUMAN SOFT TISSUE SARCOMAS BEFORE AND AFTER HYPERTHERMIC ISOLATED LIMB PERFUSION WITH TNF” AND MELPHALAN

Komdeur R, Molenaar WM, de Jong S, Hoekstra HJ, Plaat BEC, Van den Berg E, Van der Graaf WTA (University Hospital Groningen, 9700 RB, the Netherlands)

Introduction: Hyperthermic isolated limb perfusion with TNF” and melphalan (HILP-TM) has improved the limb salvage rate for primarily irresectable soft tissue sarcomas (STS) of the extremity to > 75%. Apart from the effect of TNF-” on the tumor-associated vasculature, it may also act as a cytotoxic agent either directly or indirectly. TNF” can upregulate the expression of Fas Ligand (FasL) and Fas; FasL is a member of the TNF family and rapidly induces apoptosis after binding to its receptor Fas. TNF” and cytostatics may (partially) exert their anticancer effect via the Fas-FasL pathway.

Objectives: (1.) To determine whether the expression of FasL and Fas is changed after HILP-TM. (2.) To evaluate the relationship between FasL and Fas expression, tumor response and apoptotic index. Patients, methods: 35 patients with a primarily irresectable extremity STS underwent HILP with TNF” (3-4 mg) and melphalan (10-13 mg/L limb volume). The median period between HILP and resection of the tumor remnant was 60 days (range 12-103). Tumor-samples were collected from the diagnostic pre-HILP specimen and from the post-HILP resection specimen. For assessment of tumor response and immunohistochemical analysis of FasL and Fas, see Tables 1 and 2. Using the TUNEL-method, the apoptotic index was quantified as the percentage of apoptotic tumor cells.

Results: 6 patients had CR (17%), leaving no viable tumor tissue for immunohistochemistry; 25 patients revealed a PR (71%); 4 patients had NC (11%). Before HILP, 15/33 (45%) and 15/19 (79%) samples scored positive for FasL and Fas, respectively (Fig.1 and 3). After HILP, the samples for FasL and Fas stained positively in 11/28 (39%) and 13/15 (87%), respectively (Fig. 2 and 4). For evaluable paired samples taken before and after HILP, no significant changes in FasL or Fas were seen. The mean percentage of apoptotic cells increased from 0.91 to 2.09% after HILP (p<0.05). Statistical analysis revealed no correlation between FasL/Fas expression and tumor response or apoptotic index.

Conclusions: No significant changes were found in FasL and Fas expression after HILP-TM. FasL and Fas expression did not predict the tumor response to HILP-TM or apoptosis. However, these results may be influenced by the protracted period between HILP and tumor resection and absence of evaluable tumor tissue after HILP-TM in patients with CR.