Fatty Acid Hydrolase Is Preferentially Expressed in Pulmonary Carcinoid Tumors
Konstantin Shilo, Janani Ravi, Mohd Nasser, David Cohen, Weiqiang Zhao, Miguel Villalona, Jun Fukuoka, Jin Jen, Teri Franks, William Travis, Ramesh Ganju. Ohio State University, Columbus, OH; Toyama University, Toyama, Japan; Mayo Clinic, Rochester, MN; JPC, Silver Spring, MD; Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Synthetic cannabinoids and the endocannabinoid system have been shown to play a role in inhibiting cancer cell proliferation and metastases in some solid tumor malignancies including non-small cell lung carcinoma. Endocannabinoids are degraded by various enzymes, including fatty acid amide hydrolase (FAAH) and thus enzymes catalyzing endocannabinoid hydrolysis represent potential new targets for cancer pharmacotherapies. The goals of this study were to investigate FAAH expression in a large cohort of pulmonary neuroendocrine tumors (NET) and to assess its possible association with clinicopathological variables.
Design: Clinicopathological features of 178 patients with NET including 48 typical carcinoids (TC), 31 atypical carcinoids (AC), 27 large cell neuroendocrine carcinomas (LCNEC), and 72 small cell lung carcinomas (SCLC) were analyzed with regard to FAAH expression utilizing tissue microarray based samples. Immunohistochemical staining (1:200, rabbit polyclonal antibody, Alpha Diagnostics, San Antonio, TX) was assessed in comparison to normal pulmonary parenchyma and recorded as: 0 (negative), 1+ (low) or, 2+ (higher than in normal bronchiolar epithelium or positive). Correlation of FAAH expression with clinical-pathological variables was performed utilizing SYSTAT13.0 (SPSS Inc., Chicago, IL).
Results: FAAH expression was seen in tumor cells as diffuse cytoplasmic staining of variable intensity. Low levels of FAAH were present in normal bronchiolar epithelium but not in alveolar parenchyma. High levels of FAAH expression was identified in 48/126 (38.1%) of pulmonary NET, including 18/34 (53.0%) of TC, 14/27 (51.9%) of AC, 5/20 (25.0%) of LCNEC and 11/45 (24.4%) of SCLC. FAAH was more frequently detected in carcinoid tumors (52.5%) than in high grade NET (24.6%), p=0.001 and its expression correlated with tumor grade, p=0.02. No correlation between FAAH and patients' age, gender, tumor size, stage or outcome was identified.
Conclusions: FAAH expression is observed in a significant percentage of pulmonary NET and shows correlation with the tumor grade. FAAH is preferentially expressed in carcinoid tumors, suggesting that FAAH may lead to the degradation of endocannabinoids, thereby preventing the anti-tumorigenic effects of these compounds. Further investigation of FAAH and other endocannabinoid molecules as potential targets for therapy of NET is warranted.
Monday, March 4, 2013 1:00 PM
Poster Session II # 300, Monday Afternoon