e18507 Background: NFkB pathways have become objects of detailed research in the last years, although, little is known of the possible role of BCL3 in lung carcinogenesis. The aim of this study was to define the relation of the BCL3 single nucleotide polymorphism rs8100239 with NSCLC and its association with BCL3 protein expression. Methods: Using Tagger and Sysnps programs, we chose the rs8100239 polymorphism of BCL3.We used 294 blood and FFPE normal tissue specimens from patients with NSCLC and 280 blood specimens from healthy donors. DNA isolation was performed using the Qiagen DNA blood and the QIAamp DNΑ FFPE Tissue kits. Samples were genotyped using real-time PCR. Immunohistochemical analysis for BCL3 was performed on 90 FFPE specimens (80 tumors and 10 tumor-adjacent normal tissues) from NSCLC patients. Results: Approximately half of the healthy donors (45.5%) were AT heterozygotes, 36.6% were TT and 17.9% were AA homozygotes. The respective frequencies in patients were 43.8%, 33.1% and 23.1%. There was no statistically significant difference in allele frequencies between healthy controls and patients (p=0.297). However, patients of stage II carrying a T allele displayed two and five-year survival benefit compared to patients with AA genotype (p<0.001). Immunohistochemical analysis for BCL3 protein revealed a statistically significant difference between malignant and normal lung tissue (p<0.001). More specifically, BCL3 was detected in both the cytoplasm and nucleus in neoplastic tissues with strong intensity, whereas in non neoplastic tissue no immunostaining was noticed. BCL3 protein levels were not associated with the polymorphism. However, cytoplasmic expression of BCL3 was correlated with age (p=0.009), histological subtype (p=0.031) and disease stage (0.038). Furthermore, tumors with smaller diameter had higher BCL3 nuclear expression levels than larger tumors (p=0.009). Conclusions: Patients of stage II carrying a T allele had improved two and five-year survival. BCL3 expression is not correlated with rs8100239 status. However, it is related to histological subtype, stage and maximum diameter while it differs between malignant and normal lung tissue. This research has been co-financed by the EU and Greek national funds (Heracleitus II Program).