Posters— Oncology Research

A CASE OF GASTROINTESINAL SARCOMA TUMOR (GIST) REVEALED BY A HYPOXIA IN HUMAN SOFT TISSUE SARCOMAS: ADVERSE IMPACT ON SURVIVAL AND NO ASSOCIATION WITH p53 MUTATIONS

M. Nordsmark^1,2, J. Alsner¹ , J. Keller³, O.S. Nielsen², O.M. Jensen⁴ and J. Overgaard¹. ¹Danish Cancer Society, Departments of Experimental Clinical Oncology, ²Oncology, ³Orthopaedic Surgery and ⁴Pathology, Aarhus University Hospital. Nörrebrogade 44, bldg 5 (DK-8000 Aarhus C, Denmark)

Preclinical studies have suggested that cells with mutations in the tumour suppressor gene, p53 have a reduced apoptotic potential under hypoxic conditions and that this may lead to progression of neoplastic cells into a more malignant phenotype. The present study correlated tumour oxygenation and p53 status in human soft tissue sarcomas (STS) and compared oxygenation status with treatment outcome after five years follow-up. Pretreatment tumour oxygenation measurements were done in 33 patients with STS using polarographic needle electrodes (Eppendorf, Germany) and status of the p53 gene was determined in 32 of those by PCR using DNA extracted from paraffin-embedded (n=2) sections or frozen biopsies (n=30). Overall median of the tumour median pO2 was 15 mmHg (range 1-58 mmHg). Only 6 tumours had p53 mutations and no association was found between mutant p53 and hypoxia. Twenty-eight cases could be evaluated by actuarial survival estimates. At a median follow-up of 74 months 12 patients had died. When stratifying into welloxygenated and hypoxic tumours by overall median pO2 patients with hypoxic tumours had a poorer disease specific survival probability (Log rank, p=0.05) and a poorer overall survival (Log rank, p= 0.01) at five years. In conclusion we demonstrated that hypoxia was a marker for metastatic disease and poorer overall survival in human STS. Moreover, tumour oxygenation and p53 status were not associated.

Supported by grant form the Danish Cancer Society.