Purpose: Thioredoxin (TRX), a low molecular weight protein, exerts reduction-oxidation control over a number of transcription factors involved in cell activation and proliferation. High TRX mRNA levels have been found in lung carcinomas, a trait associated with a growth and survival advantage.

Experimental Design: In this study, we examined the immunohistochemical expression 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 respiratory bronchial epithelium, alveolar epithelium, and alveolar macrophages. Bronchial glandular cells demonstrated a mixed nuclear and cytoplasmic staining. In lung carcinomas, the pattern of expression for TRX was predominantly cytoplasmic and only occasionally nuclear. A strong association between absence of TRX expression and regional lymph node negativity was observed (P = 0.004). High proliferation index, as detected with Ki-67 antibody, was associated with high TRX expression (P = 0.02). A significant correlation between 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 endonuclease 1 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 associated with bad prognostic features and possibly with a poorer outcome.