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Thioredoxin Expression Is Associated with Lymph Node Status and Prognosis in Early Operable Non-Small Cell Lung Cancer¹

Department of Clinical Oncology, University General Hospital of Heraklion, Heraklion 71110, Crete, Greece [S. K., J. S., V. G.]; Department of Pathology, Democritus University of Thrace, Alexandroupolis G8100, Greece [A. G., E. S.]; Department of Radiotherapy and Oncology, University General Hospital of Larissa, Larissa 41222, Greece [M. K.]; Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724-5024 [G. P.]; and Department of Cellular Science [K. C. G.] and Imperial Cancer Research Fund Molecular Oncology Laboratory [A. L. H.], John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom

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.

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