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

Abstract

The beneficial effects of cyclo-oxygenase (COX) inhibitors in both colon cancer and adenomatous polyps suggest a role for the prostanoid pathway in epithelial malignancy. Although variable prostanoid synthesis in non-small cell 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-1) and inducible COX (COX-2) by means of in situ hybridization and immunohistochemistry. COX-1 mRNA expression was absent or below the level of detection via in situ hybridization. COX-1 immunohistochemistry demonstrated uniform faint cytoplasmic staining in tumour cells and stromal inflammatory cells. Semiquantitative 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 with large cell and squamous cell carcinoma), intermediate and variable expression in large cell carcinoma (n=11) and low or absent expression in squamous cell tumours (n=13). Levels of COX-2 expression in infiltrating inflammatory 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-small cell lung cancer, and primary lung adenocarcinoma expresses the highest levels of cyclooxygenase-2. Assessment of cyclo-oxygenase-2 expression ex vivo should be performed in studies examining the potential therapeutic effects of cyclo-oxygenase inhibitors in non-small cell lung cancer.

• Authors: D N Watkins, J C Lenzo, A Segal, M J Garlepp, P J Thompson
• Journal: The European respiratory journal (Eur Respir J) Vol. 14 Issue 2 Pg. 412-8 (Aug 1999) ISSN: 0903-1936 [Print] England
• PMID: 10515422 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isoenzymes
• Membrane Proteins
• RNA, Messenger
• Cyclooxygenase 1
• Cyclooxygenase 2
• PTGS1 protein, human
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases

Topics

• Carcinoma, Non-Small-Cell Lung (enzymology, genetics, pathology)
• Cyclooxygenase 1
• Cyclooxygenase 2
• Gene Expression Regulation, Enzymologic (physiology)
• Humans
• Isoenzymes (genetics)
• Lung (enzymology, pathology)
• Lung Neoplasms (enzymology, genetics, pathology)
• Membrane Proteins
• Prognosis
• Prostaglandin-Endoperoxide Synthases (genetics)
• RNA, Messenger (genetics)