The concept of “field defect” or “field cancerization” in carcinogenesis originates from a report about the frequent multiplicity of oral squamous cell carcinoma in 1953.
1 Simultaneous occurrence of multiple adenomas or sequential recurrence of adenomas after curative removal of the primary tumor suggests the presence of field defects; it might contribute to tumor development in colon carcinogenesis.
2,3 Several studies have found differences in the molecular characteristics of cancerous tissues and matched normal colonic tissues. According to these studies, CEA, O6-methylguanine-DNA methyltransferase (MGMT) gene promoter, and cyclooxygenase-2 (COX-2) have been suggested as field defect markers in colon carcinogenesis.
4,5,6 Of these, COX-2 is overexpressed in human colon cancer, and it contributes to the carcinogenesis by producing prostaglandin E
2 (PGE
2).
7,8,9,10,11 In addition to COX-2, 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and microsomal prostaglandin E synthase-1 (mPGEs-1) play important roles in colon carcinogenesis. The expression of 15-PGDH, which converts biologically active PGE
2 to inactive keto-PGE
2, is markedly reduced in colonic neoplasia;
12,13,14 it has been also shown to be a tumor suppressor in human gastrointestinal carcinogenesis.
12,15,16,17 On the other hand, mPGEs-1, which converts prostaglandin H
2 (PGH
2) to PGE
2, was found to be overexpressed in human colorectal adenoma and adenocarcinoma, compared to the matched normal tissues.
18 Therefore, as a continuum of PGE
2 production in colorectal carcinogenesis, suppression of 15-PGDH and overexpression of COX-2 and mPGEs-1 are anticipated in colorectal neoplasm. We previous suggested that 15-PGDH in the normal colorectal mucosa is a potential biomarker of the field effect in carcinogenesis.
14 However, the potential usefulness of COX-2, 15-PGDH, and mPGEs-1 as a set of diagnostic or phenotypic markers for field defect in colon carcinogenesis has not been evaluated. If the expression gradient of COX-2 and 15-PGDH in the normal colonic mucosa is present and is related to the distance from the neoplastic tissue, these molecules can be suggested to be field defect markers. Moreover, if COX-2, mPGEs-1, 15-PGDH, and PGE
2 are markers of field defects in colon carcinogenesis, the expression or level of these molecules may differ between the normal tissues matched with adenoma and the normal tissues matched with adenocarcinoma. We evaluated the expression of COX-2, mPGEs-1, and 15-PGDH in human colonic neoplasms and matched normal tissues to assess the potential of these enzymes as field defect markers in colon carcinogenesis.