Thioredoxin expression is associated with lymph node status and prognosis in early operable non-small cell lung cancer

Purpose: Thioredoxin (TRX), a low molecular weight protein, exerts reductio n- oxidation control over a number of transcription factors involved in cel l activation and proliferation. High TRX mRNA levels have been found in lun g carcinomas, a trait associated with a growth and survival advantage. Experimental Design: In this study, we examined the immunohistochemical exp ression of human TRX in normal lung and in 102 primary non-small cell lung carcinomas. Results: In normal lung, the staining for TRX was cytoplasmic in the respir atory bronchial epithelium, alveolar epithelium, and alveolar macrophages. Bronchial glandular cells demonstrated a mixed nuclear and cytoplasmic stai ning. In lung carcinomas, the pattern of expression for TRX was predominant ly cytoplasmic and only occasionally nuclear. A strong association between absence of TRX expression and regional lymph node negativity was observe (P = 0.004). High proliferation index, as detected with Ki-67 antibody, was a ssociated with high TRX expression (P = 0.02). A significant correlation be tween high cytoplasmic p53 reactivity and low TRX expression was observed ( P = 0.04). No association with grade, tumor stage, histology, or bcl-2 was noted. A significant coexpression of TRX with human activator protein endon uclease I was recorded (P = 0.04). Absence of TRX expression was associated with a better outcome (P < 0.05). Conclusions: We conclude that overexpression of TRX in non-small cell lung carcinomas is indicative of a more aggressive tumor phenotype and is associ ated with bad prognostic features and possibly with a poorer outcome.