Immunohistochemical expression of nuclear factor kappa-B/p65 and cyclooxygenase-2 in non-small cell lung cancer patients: Prognostic value and impact on survival

Nuclear factor kappa B/p65 [NF-KB/p65] regulates the expression of various molecules important in tumorigenesis as cyclooxygenase-2 [COX-2]. To study the immunohistochemical expression of NF-KB/p65 and COX-2 in NSCLC, investigate the relationship between their expression and the clinicopathological parameters, evaluate their prognostic value and clarify their impact on survival. Fifty NSCLC patients were enrolled in this study and subjected to: full medical history and physical examination, routinelaboratory tests and CT chest. Fiberoptic bronchos-copy was done and biopsies were taken from visible masses and 20 mucosal biopsies of the same patients [as control]; sent for histopathological and immunohistochemical examination using anti-COX2 and anti-NF-KB/p65 antibodies. The median follow up of patients was 13 [range 4-22 months]. Results: Thirty six [72%] showed positive NF-icB/p65 expression, it was higher in squamous cell carcinoma and adenocarcinoma than in normal biopsies. Adenocarcinoma showed higher NF-KB/ p65 positivity compared to squamous and large cell carcinomas. A significant relationship was found between NF-KB/p65 expression and overall survival. Forty five [90%] showed positive COX-2 expression, no expression was detected in normal biopsies. COX-2 expression was significantly higher in adenocarcinoma compared to squamous and large cell carcinomas. NF-KB/p65 and COX-2 expression was significantly correlated with advanced tumor stage, lymph node metastasis and grade. A significant positive relationship was found between NF-KB/p65 and COX-2 expression. NF-KB/P65 and COX-2 expression has a prognostic value in NSCLC, they are suitable targets for development of new lung cancer therapies; inhibition of NF-KB and COX-2 will augment the efficacy of anticancer therapy

utility of survivin mRNA as a diagnostic biomarker in lung cancer with malignant pleural effusion

The sensitivity of conventional cytology for the detection of malignant cells in pleural effusion is insufficient. Since survivin is frequently overexpressed in lung cancer, it might play a role in oncogenesis and progression of the tumor. To evaluate diagnostic value of survivin mRNA expression in lung cancer with pleural effusion. Sixty-five pleural fluid specimens were collected from lung cancer patients [group I]. Twenty benign pleural fluid specimens were also collected [group II], considered to be control group, and this group was classified into transudate and exudate according to Light's criteria. Real time Polymerase chain reaction [RT-PCR] was performed to detect the survivin mRNA expression in the pleural fluid specimens. The sensitivity, specificity and accuracy were calculated by using receiver operating characteristic [ROC] analysis. Sixty-five pleural fluid specimens from lung cancer patients were tested by RT-PCR, only 30/65 [46%] had positive cytology. The positive rate of survivin mRNA expression in maligant pleural effusion [63/65; 95.38%] was much higher than that in the pleural effusion with benign disease [4/20; 20%, P < 0.01]. Twenty-seven cancer patients were negative for cytology and 24/27 were positive for survivin mRNA expression. The sensitivity, specificity and accuracy of survivin were 89.5%, 50%, 73.1% for diagnosing malignant pleural effusion. The detection of survivin by RT-PCR seems to be a promising assay to diagnose malignant pleural effusions, using the appropriate cut-off point, survivin mRNA has a significant role in differentiating benign from malignant pleural effusion