3.P.45 SURVIVIN, DR4 AND DR5: POTENTIAL TARGETS IN FUTURE THERAPY STRATEGIES FOR CHORDOMAS?

Abstract

Chordomas are rare neoplasms originating from notochordal remnants. They usually affect the midline and the standard treatment consists of surgery and radiotherapy. The present study investigates the expression of survivin, DR4 and DR5 to evaluate potential molecular targets for future therapy-strategies.

The study-group included 33 chordomas obtained from 21 male and 9 female patients. At time of diagnosis the patients’ age ranged from 24 to 80 years (51.9 ys.). Tumours were located on the scull-base, in the sacral/coccygeal area and the column in 13, 10, and 7 cases, respectively. Tumour-volume, known in 16 cases, ranged from 3.6 to 668.2 cm3 (mean size 130.7cm3). Immunohistochemistry was performed with antibodies against survivin, DR4, DR5. The staining pattern (cytoplasmic and/or nuclear), percentage of positive tumour-cells and staining-intensity were evaluated.

Histologically the tumours were classified as classic, chondroid and dedifferentiated chordomas in 27, 2 and 1 case, respectively. Survivin expression was obtained in 87.5% of the cases. The staining pattern was cytoplasmic in all cases and an additional nuclear staining was detected in two. Staining-intensity was predominantly weak. In 87.9% of cases DR4 staining was investigated in more than 10% of the tumour-cells. The immunoreaction was cytoplasmic (87.9%) and a nuclear staining was additionally detected in two cases. The staining-intensity was predominantly weak. In 81.8% of the chordomas DR5 staining was obtained in more than 10% of the tumour-cells. The staining pattern was cytoplasmic (84.4%) and in one case cytoplasmic and nuclear. The staining-intensity was predominantly moderate.

We hypothesise, based on the availability of new chemo- or immunotherapeutic agents like Mapatumumab (agonistic human monoclonal antibody to DR4, tested in solid tumours) and YM155 (new small-molecular inhibitor of survivin, tested in solid tumours and lymphoma), that survivin, DR4 and DR5 may act as potential molecular targets in future therapy of chordomas.