Hypoxia in human soft tissue sarcomas: adverse impact on survival and no association with p53 mutations.
Clinical and experimental studies have suggested that tumour hypoxia is associated with poor treatment outcome and that loss of apoptotic potential may play a role in malignant progression of neoplastic cells. The tumour suppressor gene p53 induces apoptosis under certain conditions and microenvironmental tumour hypoxia may select for mutant tumour cells with diminished apoptotic potential due to lack of p53 function. The aim of this study was to evaluate the prognostic relevance of oxygenation status for treatment outcome and to compare pre-treatment tumour oxygenation measurements were done in 31 of those by PCR using DNA extracted from paraffin-embaedded sections (n = 2) or frozen biopsies (n = 29). The overall median of the tumour median pO(2)was 19 mmHg (range 1-58 mmHg). Only 6 tumours had functional p53 mutations and no association was found between mutant p53 and tumour hypoxia. Five out of 6 STS with lower histopathological grade were well-oxygenated whereas high-grade STS were both hypoxic and well-oxygenated. At a median follow-up of 74 months, 16 patients were still alive among 28 available for survival analysis. When stratifying into hypoxic and well-oxygenated tumours patients with the most hypoxic tumours has a statistically poorer disease-specific and overall survival at 5 years. In conclusion hypoxia was an indicator for both a poorer disease specific and overall survival in human STS but hypoxic tumours were not characterized by mutations in the p53 gene.
Nordsmark
M
M
Danish Cancer Society Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark.
Alsner
J
J
Keller
J
J
Nielsen
O S
OS
Jensen
O M
OM
Horsman
M R
MR
Overgaard
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D015687:Cell Hypoxia; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D011379:Prognosis; D012509:Sarcoma / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D015415:Biomarkers; D016159:Tumor Suppressor Protein p53; D010100:Oxygen