Expression of inflammatory modulator COX-2 in pancreatic ductal adenocarcinoma and its relationship to pathologic and clinical parameters

Despite the exceedingly poor prognosis of pancreatic cancer, it is often hi stologically well to moderately differentiated. The apparent resistance to conventional therapeutic modalities is poorly understood and may be related to the molecules involved in its progression or its propensity for perineu rial invasion, Cyclooxygenase-2 (COX-2) is an inducible enzyme homologous t o COX-1 that is responsible for production of prostaglandins at sites of in flammation, It is activated by a variety of growth factors and tumor promot ers, and it has been implicated in cancer progression. It may also have a r ole in the resistance to therapy. Anti-COX-2 agents have been documented to have antitumor activity, and some are now being tested in the therapy for various cancers, including those of the pancreas. Experience regarding the rate of COX-2 expression in pancreatic cancer and its relationship to the c linical and biologic parameters is very limited. In this study, immunohisto chemical stains for COX-2 have been performed on 120 cases of pancreatic du ctal adenocarcinoma. The stains were scored according to the percentage (0: no staining, 1: < 10%, 2: 10-50%, and 3: > 50% of the cells staining) and intensity (0 for no staining, 1 for mild staining, and 2 for dark staining) of staining. Based on the combined score for each case, they were divided into low expressors (percentage and intensity less than or equal to1) and h igh expressors (percentage or intensity >1). In addition to global scoring for each case, the glandular and solid (poorly differentiated) components, when present, were scored separately. The global scores were correlated wit h clinical and biologic parameters. Seventy-four percent of the cases exhib ited expression of COX-2 and 53% were high expressors. No significant assoc iation was observed when comparing the global COX-2 expression to survival, tumor size, stage and vascular invasion. Increased perineural invasion was found to be significantly associated with COX-2 expression (p < 0.05). Inc reased expression was also more common in the glandular component as compar ed with the solid component of the tumors (68% versus 35%, p < 0.05). Of th e 34 patients who received radiotherapy, 9 were low expressor (median survi val 19.5 months) and 25 were high expressors (median survival 14 months). T he difference in survival was not statistically significant.