Expression of Aldo-Keto Reductase Family 1 Member C3 (AKR1C3) in Normal and Neoplastic Lung
Paari Murugan, Valerie Miller, Hsueh-Kung Lin, Kar-Ming Fung. University of Oklahoma Health Sciences Center, Oklahoma City, OK
Background: The polycyclic aromatic hydrocarbons (PAH) in tobacco smoke and air pollution require activation to electrophilic metabolites in order to exert their carcinogenic or mutagenic effects. Human aldo-keto reductase (AKR) isoenzymes, despite detoxifying harmful reactive oxygen species, may catalyze formation of deleterious PAH o-quinones and thus play an important role in PAH induced lung carcinogenesis. AKR1C3, or type 2 3α/type 5 17β-hydroxysteroid dehydrogenase, is a multifunctional isoenzyme of the AKR superfamily. It has been suggested that AKR1C3 modulates the risk of lung cancer arising from exposure to PAH-rich environments. We studied the expression of AKR1C3 in normal and neoplastic lung tissue.
Design: Immunohistochemistry for AKR1C3 was performed on formalin-fixed, paraffin embedded sections of 15 small cell carcinomas, 14 adenocarcinomas and 18 squamous cell carcinomas of the lung. The normal tissue sections were obtained from areas uninvolved by tumor in these cases. Immunoreactivity was scored as negative (<5%), 1+ (6-25%), 2+ (26-75%) and 3+ (76-100%). Appropriate controls were employed.
Results: Normal bronchial epithelium was strongly immunoreactive for AKR1C3. In the alveolar parenchyma, the type II pneumocytes were non-reactive but cytoplasmic immuoreactivity was noted in the alveolar macrophages. Out of the 18 cases of squamous cell carcinoma, 15 showed positive staining (83.3%, 3+:12, 2+:3) while 12 out of 14 adenocarcinomas stained positive (85.7%, 3+:4, 2+:7, 1+:1). In contrast, all 14 cases of small cell carcinoma were completely negative.
Conclusions: The presence of AKR1C3 in normal bronchial epithelium reflects its putative protective role against reactive oxygen species. However, the increased expression in non-small lung carcinomas demonstrates the carcinogenic potential of the enzyme, raising the possibility of a potential therapeutic target. Small cell lung carcinomas, although strongly associated with smoking, do not appear to share the same pathway. AKR1C3 could also be used as an adjunct marker to differentiate small cell from non-small cell lung carcinomas. The association between elevated AKR1C3 expression and carcinogenesis, as well as related progression of non-small cell lung cancers requires further study.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 311, Wednesday Morning