5-Lipoxygenase is Coexpressed with Cox-2 in Sporadic Colorectal Cancer: A Correlation with Advanced Stage Valeria Barresi, M.D., 1 Maddalena Grosso, M.D., 2 Enrica Vitarelli, Bbs., 2 Giovanni Tuccari, M.D., 2 Gaetano Barresi, M.D. 2 1 Dottorato di Ricerca in Oncologia Clinica, Sperimentale Applicata e Ricerca Translazionale sui Tumori, Universita ` di Messina, Messina, Italy 2 Dipartimento di Patologia Umana, Universita ` di Messina, Messina, Italy PURPOSE: It has been extensively documented that the cyclooxygenase inducible form and 15-lipoxygenase are implicated in colorectal carcinogenesis. Nonetheless, the role of other enzymes involved in the arachidonic acid metabolism, such as 5-lipoxygenase, in colorectal neo- plasms has not been fully ascertained. This study was designed to evaluate 5-lipoxygenase expression in sporadic colorectal adenocarcinomas by using immunohistochemis- try and to analyze its potential correlations with clinico- pathologic parameters and with cyclooxygenase-2 expression. METHODS: Expression of 5-lipoxygenase and cyclooxygenase-2 were evaluated by immunohistochem- istry in 50 surgically resected sporadic colorectal adeno- carcinomas (28 male and 22 female patients age range, 47–88 (mean age, 69T8) years). The chi-squared and Spearman correlation tests were used to analyze correla- tions with clinicopathologic characteristics and to evaluate any relationships between expression of the two enzymes. P values <0.05 were considered statistically significant. RESULTS: 5-Lipooxygenase and cyclooxygenase-2 immu- nostaining was found in the cytoplasm of neoplastic cells in 41 (82 percent) and in 43 cases (86 percent), respec- tively. Spearman correlation test demonstrated a positive correlation in the expression of the two enzymes. A statistically significant correlation also was observed be- tween 5-lipoxygenase expression and tumor stage and lymph node metastasis, whereas no significant correlations emerged regarding cyclooxygenase-2 expression and clin- icopathologic parameters. CONCLUSIONS: Our study demonstrates that 5-lipoxygenase is expressed in colorec- tal adenocarcinomas in association with cyclooxygenase-2 expression. Moreover, an elevated expression of this enzyme seems to be significantly correlated with tumor aggressive- ness. Further studies would clarify the need for target therapies inhibiting both metabolic pathways in such tumors. [Key words: 5-lipoxygenase; Cyclooxygenase-2; Colorectal carcinoma; Immunohistochemistry] A rachidonic acid, a fatty acid mainly derived from dietary sources, is metabolized by three major pathways: 1) cyclooxygenase (COX) pathway, which leads to the formation of prostaglandins (PGs); 2) lipoxygenase (LO) pathway, which forms hydro- peroxyeicosatetraenoic acids (HPETEs), hydroxy- eicosatetraenoic acids (HETEs), and leukotrienes, and 3) cytochrome P-450 monooxygenase pathway, which leads to the formation of epoxydes. 1,2 To date, three COX isoforms (COX-1, COX-2, and COX-3) have been identified. 3 COX-1 is expressed in most tissues and is involved in functions of cytopro- tection, vasodilatation, and control of platelet aggre- gation. COX-2 expression is induced by various stimuli, such as hormones, cytokines, growth factors, and tumor promoters, and it significantly increases in association with inflammatory processes and carcino- Supported by the grants from the University of Messina, Messina, Italy. Presented at the meeting of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology (SIAPEC), Venice, Italy, October 4 to 5, 2006. Correspondence to: Gaetano Barresi, M.D., Dipartimento di Patologia Umana, Policlinico Universitario G. Martino, Pad. D, Via Consolare Valeria, 98125, Messina, Italy, e-mail: barresi@unime.it Dis Colon Rectum 2007; 50: 1576–1584 DOI: 10.1007/s10350-007-0311-9 * The American Society of Colon and Rectal Surgeons Published online: 16 August 2007 1576