Cyclooxygenase-2 Expression in the Hereditary Mixed Polyposis Syndrome

Abstract

Hereditary mixed polyposis syndrome (HMPS), characterized by hyperplastic, juvenile, admixed, serrated adenomas and eventually colorectal cancer, is managed by repeated polypectomy and surgery. We determined if HMPS polyps express cyclooxygenase-2 (COX-2). Nineteen recent HMPS polyps, from five family members, were stained for COX-2. Polyps' epithelium and stroma and comparison tissues (normal colonic mucosa [9], sporadic juvenile polyps [18], colorectal cancers [3]) were quantified for COX-2 by: area of staining (0-3) x intensity (0-3). Epithelial, stromal, and total scores were evaluated in relationship to histology and dysplasia. HMPS polyps COX-2 mean epithelial (5.0+/-3.0), stromal (6.9+/-1.9), and total (11.8+/-4.6) scores were significantly higher (P < 0.01) than sporadic juvenile polyps (0.6+/-0.7, 3.1+/-2.2, and 3.6+/- 2.2 respectively), while colorectal cancer scored 9, 9, and 18. There was a positive association (P < 0.01) among histology, degree of dysplasia, and COX-2 expression. COX-2 expression in HMPS polyps and its association with dysplasia suggest that chemoprevention might be a useful adjunct therapy.

Hamartomatous Polyposis Syndromes

“…If the family is large enough, linkage studies using markers from chromosome 15q13-21 should be considered. Although some evidence suggests that medical management with aspirin or COX-2 inhibitors significantly inhibit sporadic colorectal adenoma recurrences and reduce the risk for CRC8, careful screening via colonoscopy, either annually or every two years, and surveillance of all polyps found via polypectomy is the most effective method to date to prevent advanced cancers from developing. When CRC has been identified more aggressive surgical management is indicated, and either a subtotal or total colectomy should be the procedure of choice.…”

Cyclooxygenase-2 overexpression is common in serrated and non-serrated colorectal adenoma, but uncommon in hyperplastic polyp and sessile serrated polyp/adenoma

“…COX-2 has been shown to be frequently overexpressed in serrated adenomas [ 29 , 30 ], but infrequently in hyperplastic polyps [ 2 , 29 - 31 ]. COX-2 overexpression has been demonstrated in polyps in hereditary mixed polyposis syndrome [ 32 ] and familial juvenile polyposis [ 33 ], but not in fibroblastic polyps [ 34 ]. However, to our knowledge, no study has comprehensively examined COX-2 expression levels in various serrated and non-serrated colorectal neoplasias.…”

Management of Juvenile Polyposis Syndrome in Children and Adolescents

“…Cyclooxygenase-2 (COX-2) inhibitors have been considered in polyposis syndromes given the broad expression of COX-2 in adenomas in familial adenomatous polyposis (FAP) (49) and in Peutz-Jeghers polyps and in hereditary mixed polyposis syndrome (50,51). There are reports describing increased COX-2 expression in JPS related to both polyp size and presence of dysplasia (52,53).…”