Abstract 4121: Immunohistochemical characterization of xenobiotic detoxification enzymes in normal mucosal epithelium, benign tumors and carcinomas of the nasal and nasopharyngeal regions

Abstract

Abstract In a cDNA microarray analysis in nasopharyngeal cancer (NPC) patients, we found abundant RNA expression of a variety of phase I and II xenobiotic detoxification enzyme genes (CYP4B1, GSTA1, GSTA2, GSTA3, MAOB, ALDH1A1 & NQO1) in the normal nasopharyngeal (NP) biopsy tissues but a lack of expression in the tumor tissues. Phase I and II detoxification enzyme systems are responsible for catabolism & excretion of different types of hydrocarbon types of carcinogens (e.g. benzopyrene, benzoanthracene & benzochrysane) present in burnt meat and tobacco smoke plus nitrosamine types of carcinogens (e.g. N-nitrosodibutylamine) present in Chinese styled salted fish, which are associated with NPC development. To further investigate the protein expression of these carcinogen detoxification enzymes, we performed immunohistochemical staining of the detoxification enzymes in tissue microarray (TMA) slides from nasopharynx and nasal regions containing 80 malignant carcinomas, 17 metatastic carcinomas, 42 benign tumors (papilloma and polyps), 12 hyperplasia and chronic inflammation and 45 normal NP or nasal tissues. GSTA3 was the enzyme with the strongest staining in the normal epithelium in 37 TMA cores but negative or weak staining was found in 63 cores of squamous cell carcinomas (SCC) (grades I, II or III) as well as undifferentiated carcinomas. Seventeen cores of metastatic NPC in lymph nodes also had weak/negative GSTA3 staining. This weak to negative staining of GSTA3 also occurred in limited numbers of rare malignant tumors in NP or nasal regions such as basal cell carcinomas, adenoid cystic carcinomas & adenocarcinomas. In great contrast, 42 cores of benign tumors (30 cores of papillomas & 12 cases of polyps) and 12 cores of hyperplasia and chronic inflammation all had significantly stronger staining of GSTA3 than malignant carcinomas although they were still weaker than that in normal mucosal epithelium. Expression of GSTA3 mainly resides in the outer epithelial layer facing the lumen of the nasopharynx (which is in direct contact with carcinogens) with the basal proliferative layer being negative. The differential expression of the detoxification enzymes in the normal epithelium versus malignant cancers enables us to hypothesize a role of these enzymes in protecting NP or nasal region from cancer development. High expression of the enzymes in benign tumors indicates another mechanism of tumor development which could be unrelated to carcinogen insults. Further cell functional analysis is ongoing to further investigate this point. Citation Format: Victor W.S. Ma, Yuen Ping Leung, Roger K.C. Ngan, Dora L.W. Kwong, Loretta Tse, Stephen C.K. Law, Timothy T.C. Yip. Immunohistochemical characterization of xenobiotic detoxification enzymes in normal mucosal epithelium, benign tumors and carcinomas of the nasal and nasopharyngeal regions. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4121. doi:10.1158/1538-7445.AM2014-4121