A Double-Blind Placebo-Controlled Assessment of Endoscopic Change and Duodenal Cox-2 Expression in Patients with Familial Adenomatous Polyposis After Treatment With a Cox-2 Inhibitor (Rofecoxib)

Introduction

Familial adenomatous polyposis (FAP) is a well-known entity, featuring widespread neoplastic growth in the gastrointestinal tract. In the colon, 1000 of polyps develop, of which some invariably develop into carcinomas. Prophylactic colectomy at a young age is generally advised.

ABSTRACT

BACKGROUND AND AIMS

Cox-2 inhibitors have been shown to counter adenoma growth and development of malignancy of the colorectum in animals and humans. The purpose of the present study was to assess the effect of a specific Cox-2 inhibitor on duodenal adenomas in patients with familial adenomatous polyposis (FAP).

MATERIALS AND METHODS

Familial adenomatous polyposis patients (N =38) with duodenal adenomas were randomly assigned to rofecoxib (Vioxx) 25 mg or placebo in a double-blind fashion for 1 year. Endoscopy with biopsies of lesions and flat mucosa were performed before and after the treatment. Macroscopic and microscopic evaluation, immunohistochemical assessment of Cox-2 protein expression, and real-time polymerase chain reaction (PCR) analyses of COX-2 gene expression were performed. In addition, the expression of COX-2 was measured by real-time PCR in leucocytes.

RESULTS

Thirty-two patients followed the scheduled treatment for at least 9 months. The macroscopic lesions appeared unchanged after intervention, both in the treatment and placebo group. Adenomatous and normal tissue showed unchanged Cox-2 expression after treatment with rofecoxib, whereas increased staining of both adenomatous tissue and normal mucosa was shown in the placebo group. A higher concentration of Cox-2 was shown in the normal compared to adenomatous mucosa, both at baseline and after treatment. This was supported by an increased COX-2 gene expression by real-time PCR in macroscopically normal mucosa.

CONCLUSION

The reduced expression of Cox-2 in duodenal adenomatous tissue compared to normal mucosa adds to the recent findings of a great individual variation in Cox-2 expression of colorectal cancers. It may also indicate a low potential for malignancy in the duodenum of FAP patients in the Norwegian population.

Keywords

cox-2 expression, cox-2 inhibition, duodenal lesions, familial adenomatous polyposis, intervention