[A study on cyclooxygenase-2 protein expression and vasculature during experimental rat lung carcinogenesis]

There is evidence that cyclooxygenase-2(COX-2) involved in the occurrence and development of neoplasms. Elevated expression of COX-2 in carcinomas and antitumor effects of nonsteroidal antiinflammatory drug(COX-2 inhibitors) have been reported, but COX-2 expression in precancerous lesions and its association with angiogenesis is not clearly defined. The aim of this study was to investigate the expression of COX-2 protein and its association with microvessel density (MVD) during the experimental rat lung carcinogenesis.

Eighty Wistar rats were intra-leftlobar-bronchial instilled with 3-methylcholanthrene and diethylinitrosamine to induce lung squamous cell carcinoma, and ten rats were instilled lipiodol as control group. To acquire every pathological phase during the carcinogenesis, rats were sacrificed at intervals from fifteen days to nine months. COX-2 expression and MVD count in the samples of every pathological phase during the carcinogenesis were examined by immunohistochemistry. The immunohistochemical score of COX-2 was calculated by combining an estimate of the percentage of immunoreactive cells with an estimate of the staining intensity. Inter tumor MVD was marked by anti-Von Willebrand factor monoantibody.

One hundred and forty seven specimens of every pathological phase during the carcinogenesis were obtained which including fourteen hyperplasia, twenty five squamous metaplasia, thirty three dysplasia, twelve carcinoma in situ, fifty four infiltration carcinoma, nine metastasis. The expression of COX-2 and MVD count increased during rat lung carcinogenesis. COX-2 immunohistochemical score was significantly higher in dysplasia, carcinoma in situ and metastasis(P < 0.01, P < 0.05, P < 0.05 respectively), and significant increased MVD were found in carcinoma in situ, infiltration carcinoma and metastasis (P < 0.01). During carcinogenesis, there was a significant correlation between COX-2 expression and MVD(r = 0.9521, P < 0.001, b = 11.51).

COX-2 may play an important role during the carcinogenesis in experimental rat lung squamous cell carcinoma as well as its metastasis, partly by stimulating angiogenesis.