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Immunohistochemical Expression of Cyclooxygenase Isoenzymes and Downstream Enzymes in Human Lung Tumors

Department of Pathology, Justus-Liebig-University Giessen, 35385 Giessen, Germany

Purpose:Prostanoids are important mediators of pulmonary vaso- and bronchotone regulation and strongly influence inflammatory reactivity. The product of cyclooxygenase (Cox), prostaglandin H₂, is further metabolized via downstream enzymes into the different effective metabolites. The specific cellular equipment with certain downstream enzymes crucially determines the cellular reactivity by generation of functionally different prostanoid metabolites.

Experimental Design: To elucidate the role of arachidonic acid metabolism via the cyclooxygenase pathway in different human lung tumors, expression of cyclooxygenase isoenzymes (Cox-1 and Cox-2) and downstream enzymes of prostanoid metabolism was investigated in human non-small cell lung cancer and normal human lung tissue by immunohistochemical techniques.

Results: In comparison to strong Cox-1 reactivity in airways and endothelial cells of normal lung specimens, only 4 of 15 adenocarcinomas showed infrequent Cox-1 expression. All lung cancer specimens displayed an increased Cox-2 immunostaining pattern with strong reactivity in adenocarcinomas and lower reactivity in squamous cell carcinomas. Adenocarcinomas and squamous cell carcinomas were also positive for thromboxane A₂ synthase, prostaglandin D₂ synthase, and prostaglandin E₂ synthase, but not for prostacyclin synthase. Endothelial cells of vessels found within or near the tumor show extensive immunostaining of Cox-2 and thromboxane A₂ synthase, whereas endothelial cells of normal lung specimens, in contrast, expressed Cox-1 and prostacyclin synthase.

Conclusions: We conclude that non-small cell lung cancer shows a specific Cox-/downstream-enzyme expression pattern, which is specifically altered in lung tumor cells and tumor supplying vessels in contrast to normal lung tissue. This may have major impact on tumor progression and tumor-associated inflammation via an altered prostanoid metabolism with consecutive tumor-associated blood flow distribution.

Commentary

Evaluation of the Whole Prostaglandin Biosynthetic Pathway in Lung Cancer

Raymond N. DuBois
Clin. Cancer Res. 2003 9: 1577-1578. [Full Text] [PDF]

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