Monday, 10 September 2012, 14.15 -16. Objective: Intratumoral disorganized neo-vasculature induces oxygen fluctuations which contribute to tumour growth and metastatic potential. Although the activation by hypoxia of the carbonic anhydrases CAIX and CAXII is well known, responses of these proteins under reoxygenation remain to be elucidated. Method: In this study we evaluated the effects of hypoxiareoxygenation on CAIX and CAXII expression and cell proliferation in A549 and H1975 lung adenocarcinoma cell lines. We further investigated by immunohistochemistry on tissue microarray the value of the combined expression of these proteins to predict outcome in 552 NSCLC patients. Results: CAIX expression was maintained at high level after reoxygenation in contrast of the rapid CAXII downregulation, whereas the cell proliferation rate was significantly increased. Survival analyses showed that high CAIX/ low CAXII was associated with high cumulative incidence of relapse and with poor overall survival of NSCLC patients (P<0.05). Conclusion: Our results provide insight into understanding dynamic responses of CAIX and CAXII expression under tumour cells reoxygenation and demonstrate a critical role for reoxygenation on CAIX and CAXII levels that may select for aggressive lung cancer phenotype. These findings suggest that CAIX and CAXII play selective roles in tumour progression and emphasize their significant prognostic and potential therapeutic value.