Expression and localization of cyclo-oxygenase isoforms in non-small cell lung cancer

The beneficial effects of cyclo-oxgenase (COX) inhibitors in both colon can cer and adenomatous polyps suggest a role for the prostanoid pathway Tn epi thelial malignancy. Although variable prostanoid synthesis in non-small cel l lung cancer (NSCLC) has been demonstrated in freshly obtained tissue, COX messenger ribonucleic acid (mRNA) and protein localization in such tumours had not been investigated ex vivo. Thirty-four cases of primary NSCLC were examined for both constitutive (COX -I) and inducible COX (COX-2) by means of in situ hybridization and immunoh istochemistry. COX-I mRNA expression was absent or below the level of detection via in sit u hybridization. COX-I immunohistochemistry demonstrated uniform hint cytop lasmic staining in tumour cells and stromal inflammatory cells. Semiquantit ative analysis of COX-2 expression in NSCLC demonstrated the highest levels of both mRNA and protein in adenocarcinoma cells (n=10, p<0.005 compared w ith large cell and squamous cell carcinoma), intermediate and variable expr ession in large cell carcinoma (n=11) and low or absent expression in squam ous cell tumours (n=13). Levels of COX-2 expression in infiltrating inflamm atory cells was the same in all tumour types. In conclusion, tumour cell cyclo-oxygenase-2 rather than cyclo-oxygenase-1 expression may account for the variable prostanoid production seen in non-s mall cell lung cancer, and primary lung adenocarcinoma expresses the highes t levels of cyclo-oxygenase-2. Assessment of cyclo-oxygenase-2 expression e x vivo should be performed in studies examining the potential therapeutic e ffects of cyclo-oxygenase inhibitors in non-small cell lung cancer.