Cyclooxygenase-2 Overexpression Is Linked to Increased VEGFR-3 Levels in Lung Adenocarcinoma but Its Association with Survival Is of Borderline Significance
S Sethi, F Lonardo. Karmanos Cancer Center, Wayne State University and The Detroit Medical Center, Detroit, MI
Background: Cyclooxygenase-2 (Cox-2) regulates important pathways in carcinogenesis, including angiogenesis, and has been a target of molecular therapy in clinical trials, in Non Small Lung Cancer (NSCLC).Yet, it remains unclear whether its expression has a prognostic role in NSCLC and what its relation to the other molecules involved in angiogenesis is.
Design: In order to define the prognostic role of Cox-2 in NSCLC we studied whether its expression predicts prognosis, in resected adenocarcinoma (Aca) and Squamous Cell carcinoma (SqCC) and whether its expression is linked with that of Vascular Endothelial Growth Factor Receptor 3 (VEGFR3), in Aca. 59 Aca (34 stage I, 9 stage II and 16 stages III-IV; mean follow-up 131 months) and 27 SqCC (16 stage I, 6 stage II, 5 stages III-IV, mean follow-up 67 months)were evaluated for Cox-2 expression, using immunohistochemical analysis. Expression of Cox-2 and VEGFR3 were scored based on staining intensity (0;1=low to 3=highest) and percentage of positive cells (1≤10%; 2=11-50%; 3=>50%). A final score was obtained multiplying the two scores (0 to 9) and cases were classified as low (0-4) or high (6-9) expressors. Survival data were obtained through the charts and the Detroit Metropolitan Cancer Surveillance System.
Results: Kaplan-Meier survival analysis showed that high Cox-2 expression has a trend in predicting better survival in Aca, when all stages were analyzed (p=0.056), whereas it showed no statistical association with survival when only stage I were studied. In SqCC, Cox-2 levels were not predictive of survival, at any stage. In Aca, Cox-2 high expression significantly correlated with high VEGFR3 expression (p=0.037).
Conclusions: 1- The trend we found for an association with survival of Cox-2 levels, in Aca confirms most published data, supporting the hypothesis that Cox-2 does not have a major influence on the prognosis of NSCLC. 2-Cox-2 may have a different impact on the biology of Aca and SqCC, including its prognosis. This may be due to the inherently different pathobiology of these cancers. 3-The correlation of high Cox-2 expression with high VEGFR3 expression we found confirms the reported role of Cox-2 in tumor angiogenesis. However, further studies on the interaction of Cox-2 with the other growth factors, inhibitors and receptors of this pathway are needed to understand the molecular details of this interaction and its ultimate impact on vessel formation in NSCLC.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 250, Tuesday Morning