Stromal Caix Expression In Oral Squamous Cell Carcinoma And Corresponding Lymph Node Metastases

Background: Hypoxia is an almost ubiquitous feature of human solid tumours. However, the direct measurement of oxygen concentration in head and neck squamous cell carcinoma (HNSCC) has been conducted almost exclusively in the metastatic lymph nodes, not the primary tumor. Hypoxia is associated with resistance to both radiotherapy (RT) and chemotherapy in squamous cell cancers (SCCs). However, endogenous markers of hypoxia (EMH) have not reproducibly predicted clinical outcome. However, historically, the method used to assign hypoxic status according to directly measured oxygen concentration (polarographic electrode) and EMH (typically immunohistochemistry) have fundamentally differed. Methods: Demographic data and clinical outcomes of 61 patients with oral squamous cell carcinoma (OSCC) treated with primary surgery +/- adjuvant radiation were collected. Tissue microarray9s with representative samples of patients9 tumors were constructed from paraffin-embedded blocks. Automated quantitative immunohistochemistry (AQUA) was performed to measure expression and distribution of carbonic anhydrase IX (CAIX). Kaplan-Meier survival analysis and the log-rank test was used to assess the impact of vimentin-defined stromal CAIX (in both primary tumor and nodal metastases) on survival. Results: High stromal CAIX expression in the primary tumor was associated with significantly worse 5-year disease-specific survival. There was a statistically significant but relatively weak correlation between stromal CAIX expression in the primary tumor and the corresponding lymph nodes (r 2 :0.359; p=0.013). Stromal CAIX expression in the lymph node metastases was not significantly associated with 5-year disease-specific survival. Conclusions: Previous literature presenting the prognostic impact of directly measured hypoxia, using a polarographic electrode, was based predominantly on measurements from lymph nodes, not the primary tumor. Furthermore, comparisons with EMH were based solely on percentage of tumor cells that were positively stained, not the intensity of staining. We present the results of a tumor comparment-specific, quantitative fluorescent IHC method and the survival associated with EMH in the tumor microenvironment in the primary tumor and lymph node metastases. Citation Format: Shamir Chandarana, Pinaki Bose, Alexander C. Klimowicz, Stephanie K. Petrillo, Mie Konno, Luke Rudmik, Steven C. Nakoneshny, Wayne T. Matthews, Anthony M. Magliocco, Joseph C. Dort, Nigel T. Brockton. Stromal CAIX expression in oral squamous cell carcinoma and corresponding lymph node metastases. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A10.