IADR Abstract Archives
Nrf2 Expression in Oral Mucosa is Associated with Cellular Differentiation
Objectives: Overexpression of the oxidative stress (OS) response transcription factor Nrf2 is associated with poor responses to therapy in head and neck squamous cell carcinomas (HNSCC). Despite its potential role as a predictor of response to therapy, reported descriptions of the immunohistochemical (IHC) staining patterns in both normal and cancer cells are inadequate. Generally only the expression level of Nrf2 in the cell, rather than its level and localization is reported. The objective of this project is to utilize IHC staining of HNSCC formalin fixed paraffin embedded derived tissue to further define the levels and localization of Nrf2 expression in HNSCC.
Methods: Five patient tumors were IHC stained using the Abcam anti-human-Nrf2-antibody (ab31163). Each tumor contained multiple regions of histologically normal and well-, moderately-, and/or poorly-differentiated malignant tumor cells for evaluation. A semi-quantitative scale (0-3) was used to quantify the nuclear and cytoplasmic expression levels of Nrf2.
Results: The resulting staining patterns were varied and interesting. Normal oral mucosa showed intense staining in the nucleus of basal cells that lessened as cells moved towards the mucosal surface. Well-differentiated tumors exhibited primarily cytoplasmic staining while poor-moderately differentiated tumors showed more intense staining in both the cytoplasm and the nucleus.
Conclusions: The association of both Nrf2 staining intensity and Nrf2 nuclear localization to tumor grade is important. Under low OS conditions, Nrf2 is tightly regulated in the cytoplasm. Upon high OS conditions, Nrf2 translocates to the nucleus where its activity drives the OS response. In normal cells, Nrf2 activity can prevent tumorigenesis as free radicals are adequately neutralized. After malignant transformation, high Nrf2 activity in tumors blunts the effectiveness of therapies and promotes drug resistance. Nrf2 has potential value as a prognostic molecule as well as a therapeutic target so it is critical to understand its patterns of expression in normal and diseased oral mucosa.
Methods: Five patient tumors were IHC stained using the Abcam anti-human-Nrf2-antibody (ab31163). Each tumor contained multiple regions of histologically normal and well-, moderately-, and/or poorly-differentiated malignant tumor cells for evaluation. A semi-quantitative scale (0-3) was used to quantify the nuclear and cytoplasmic expression levels of Nrf2.
Results: The resulting staining patterns were varied and interesting. Normal oral mucosa showed intense staining in the nucleus of basal cells that lessened as cells moved towards the mucosal surface. Well-differentiated tumors exhibited primarily cytoplasmic staining while poor-moderately differentiated tumors showed more intense staining in both the cytoplasm and the nucleus.
Conclusions: The association of both Nrf2 staining intensity and Nrf2 nuclear localization to tumor grade is important. Under low OS conditions, Nrf2 is tightly regulated in the cytoplasm. Upon high OS conditions, Nrf2 translocates to the nucleus where its activity drives the OS response. In normal cells, Nrf2 activity can prevent tumorigenesis as free radicals are adequately neutralized. After malignant transformation, high Nrf2 activity in tumors blunts the effectiveness of therapies and promotes drug resistance. Nrf2 has potential value as a prognostic molecule as well as a therapeutic target so it is critical to understand its patterns of expression in normal and diseased oral mucosa.
