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


METHODS
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.
Kakolyris
S
S
Department of Clinical Oncology, University General Hospital of Heraklion, Heraklion 71110, Crete, Greece. georgsec@med.uch.gr
Giatromanolaki
A
A
Koukourakis
M
M
Powis
G
G
Souglakos
J
J
Sivridis
E
E
Georgoulias
V
V
Gatter
K C
KC
Harris
A L
AL
D000368:Aged; D019757:Carbon-Oxygen Lyases / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008168:Lung / Q000737:chemistry / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008198:Lymph Nodes / Q000737:chemistry / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016019:Survival Analysis; D013879:Thioredoxins / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D013879:Thioredoxins; D043223:Deoxyribonuclease IV (Phage T4-Induced); D019757:Carbon-Oxygen Lyases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase