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New findings may help to confirm how malignant mesothelioma develops, as cyclooxygenase-2 (COX-2) expression has been shown as a strong indicator of poor survival independently of other molecular markers previously thought to be involved.
Only expression of COX-2 (hazard ratio 1.143), not of cell cycle inhibitors p21 and p27, was significantly associated with survival of patients with mesothelioma in multivariate analysis. Univariate analysis showed that high expression of COX-2 and low expression of p21 and p27 significantly reduced survival (from median 12–14 weeks to 5 weeks). Expression of p53 tumour suppressor protein was not significant in survival, possibly because the tumours were positive for SV40 sequences. COX-2 expression was not apparently related to tumour type—whether epithelioid, sarcomucoid, or of mixed histological type—all of which were represented.
The study cohort comprised 29 selected patients from 35 original patients available for follow up, all of whom were from one region in Italy and had mesotheliomas positive for SV40 virus sequences and p53 and p21 as determined previously. All patients had had surgery and 13 later had radiotherapy or chemotherapy. Expression of COX-2 and p27 was determined by histochemical staining of thin sections of biopsy specimens of the tumour with specific antibody. Patient survival was calculated from operation date.
The study confirms the role of COX-2 expression in determining survival in mesothelioma but is the first to investigate in vivo a potential relation with p53 and p21 and p27, which an earlier in vitro study had suggested might have an influence.