Nuclear expression of aryl hydrocarbon receptor and prognosis for non-small lung cancer.

Abstract

10595 Background: Lung cancer is the leading cause of cancer death in many countries including Taiwan. Aryl hydrocarbon receptor (AhR) is a ligand activated transcription factor, which translocates from the cytoplasm to the nucleus after activation. Our previous studies showed the positive association between cytoplasmic AhR expression and the expression of cytochrome P450 1B1 (CYP1B1) and p53 in non-small cell carcinomas. In this study, we further investigated the association between nuclear expression (nuclear translocation) of AhR and the expression of p53 and/or CYP1B1 when the presence of nuclear translocation of AhR. We also studied the prognostic value of AhR, CYP1B1 and p53. Methods: Immunohistochemistry for AhR, CYP1B1, and p53 expression was performed on tissue microarrays containing 138 non-small cell carcinoma specimens. Results: Nuclear AhR immunohistochemical expression was detected in 29% of non-small cell carcinomas. Expression of nuclear, but not cytoplasmic, AhR, CYP1B1, and p53 was associated with advanced stage diseases. Nuclear AhR expression was associated with expression of CYP1B1 or p53 in adenocarcinomas. Univariate analysis showed that nuclear AhR- expressing tumors, p53-expressing tumors, smoking and advanced stage diseases had a negative effect on survival. Patients with nuclear AhR-positive tumors had the shortest median survival time (266 days), as compared to patients with both cytoplasmic and nuclear AhR-negative tumors who had the longest (532 days, p < 0.001). Nuclear AhR expression was also associated with poor prognosis in adenocarcinomas. When adjusted for covariates, nuclear AhR expression was independently associated with cancer death in stage III diseases. Conclusions: Nuclear AhR expression not only was associated with the expression of CYP1B1 and p53 in adenocarcinomas, but also was a negative factor for survival in adenocarcinoma patients. No significant financial relationships to disclose.