Increased expression of cyclooxygenase-2 and Ki-67 are associated with malignant transformation of pleomorphic adenoma.

OBJECTIVES

In the present study, we attempted to identify cyclooxygenase-2 (COX-2) expression and Ki-67 index in carcinoma ex-pleomorphic adenoma (Ca ex-PA) using quantitative immunohistochemical analysis and to compare the benign component of the neoplasia. We also aimed to relate the overexpression of COX-2 with the pathways of malignant transformation of Ca ex-PA as evidenced by distinct morphological features.

MATERIALS AND METHODS

Forty Ca ex-PA from patients treated at Department of Otolaryngology, Yokohama City University Medical Center, Yokohama, Japan, from 1999 to 2005, were selected. All Ca ex-PA showed only one malignant histological component: adenocarcinoma (23 cases), adenoid-cystic carcinoma (10), epithelial-myoepithelial carcinoma (7). The tissues were stained with monoclonal antibodies to COX-2 and Ki-67. The results were analyzed using quantitative immunohistochemical analysis. We also analyzed the association of the histological classification of the carcinomatous component.

RESULTS

In the immunohistochemical analysis of COX-2 and Ki-67 index, significant increase was observed in Ca ex-PA, especially with adenocarcinoma, compared to pleomorphic adenoma and sialadenitis. Quantitative assessment is more sensitive as a measure of cellular protein content as compared to standard optical density measurement.

CONCLUSIONS

The data support the hypothesis that increased COX-2 expression is associated with early events in malignant transformation of pleomorphic adenoma.