BACKGROUND:Lung cancer is the leading cause of cancer death in the world. The objective of this study was to investigate the expression of vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) in patients with nonsmall cell lung cancer (NSCLC) and its correlation with the prognosis for patients with lung cancer.METHODS:The expression status of VEGFs and VEGFRs was examined in 48 nonconsecutive specimens of primary lung cancer by immunohistochemistry. Correlations between the expression of VEGFs and VEGFRs and clinicopathologic parameters were analyzed.RESULTS:Nineteen of 48 samples (39.6%) were moderately/highly immunoreactive for VEGF‐A, 6 samples (12.5%) were reactive for VEGF‐B, 14 samples (29.2%) were reactive for VEGF‐C, 11 samples (22.9%) were reactive for VEGF‐D, 20 samples (41.7%) were reactive for VEGFR1, 26 samples (54.2%) were reactive for VEGFR2, 20 samples (41.7%) were reactive for VEGFR3, and 19 samples (39.6%) were reactive for nuclear expression of VEGFR3. Patients with moderate/high VEGF‐C, VEGFR1, and VEGFR2 expression had worse survival, whereas patients with moderate/high VEGF‐D and nuclear VEGFR3 expression had better survival. After adjusting according to tumor stage, VEGF‐B and VEGF‐D expression had a significant correlation with worse survival in patients with stage I and II disease. Patients with stage III and IV disease who had VEGFR1 and VEGFR2 expression had worse survival, whereas the expression of VEGF‐D was correlated significantly with better survival. Finally, stage, VEGF‐D expression, and VEGFR1 expression were significantly independent prognostic predictors.CONCLUSIONS:The results of the current study indicated that the over‐expression of VEGFs and VEGFRs plays an important role in the survival of patients with NSCLC. The inclusion of angiogenic factors in the standard pathologic study of lung cancer may improve the clinical evaluation of patients with NSCLC. Cancer 2009. © 2009 American Cancer Society.

15616 Background: Bladder cancer predominates in males. Loss of androgen receptor (AR) has been associated with invasive and undifferentiated tumors but little is known about the role of hormonal receptors in this type of cancer. Methods: We evaluated samples from 41 nonconsecutive patients treated for bladder transitional cell carcinoma between 2001–2003. Immunohistochemistry was performed using anti-AR and anti-ER a,b antibodies on paraffin-embedded tumors from transurethral resections, nuclear expression was assessed. Western blotting for AR and pAKT were performed in 22 transurethral resections from nonconsecutive bladder cancer patients treated between 2004–2006. Chi-square and U Mann-Witney tests were performed. Results: Immunohistochemistry study: the male/female ratio was 9/1; 61% were noninvasive tumors (pTa, is,1) and 32% were invasive (pT2,3); 22% were G1 and 75% were G2,3. 95% were AR(+), 40% ERa(+) and 94% ERb(+). Significant differences in AR expression were observed between G1 78% and G2,3 tumors 100%, with a high grade tumor prevalence in the AR(+) tumors 81.6% p=0.046. No differences between ERa,b and differentiation were found. G2,3 tumors were predominantly ERb(+). AR was found in 92% noninvasive and in 100% invasive tumors p=0.53. No significant differences were found between invasiveness and ERa,b. Noninvasive tumors showed higher ERa,b expresión (54%, 95% respectively) than invasive tumors (20%, 91% respectively). Western blotting group: 54.5% were primary tumors and 45.5% were recidives. The noninvasive/invasive rate was 59/32%, the G1/G2,3 rate was 4.5/95.5%. 112, 250 and 160 kDa bands were found. AR/pAKT rate was 86.4/100%. 100% of invasive tumors and 86% G2,3 tumors were AR(+). No differences between pAKT, invasiveness, differentiation or AR expression were observed but recidivated tumors had a slight higher median expression level. Conclusions: AR is positively related to tumor grade and might be involved in bladder cancer progression. The profile of AR bands suggest covalent modifications, due to ubiquitin-mediated degradation or to activation mechanisms mediated by SUMO. Nuclear AR and the absence of bands under 90kDa suggest that activated protein is present in bladder cancer. pAKT/AR inhibitors could play a role for bladder cancer therapy. No significant financial relationships to disclose.

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21135 Background: The mechanism through wich zoledronic acid exerts its activity is poorly understood. Low density lipoprotein receptor (LDLR) and scavenger receptor class B type 1 (SRBI) overproduction is an important mechanism in cancer cells for obtaining more essential fatty acids and cell growth. The effects of in vitro zoledronate treatment on the lipid metabolism of prostate cancer cell lines were studied. Methods: Three prostatic cancer cell lines, androgen insensitive PC3, androgen dependent low-passage (LP) LNCaP and androgen independent high-passage (HP) LNCaP cells were studied. Cells were plated either in RPMI with 5% foetal calf serum and lipoprotein depleted serum (LPDS) and were treated with zoledronate at different concentrations. The lipid transporters profile was analyzed by western blotting for LDLR and SRB1. Results: The same LDLR bands profile was observed in all cell lines, 160 and 105 kDa. The basal levels of LDLR were higher in the PC3 cells. Zoledronate therapy induced LDLR expression in all cell lines but PC3 were less sensitive to this effect. Cells cultured with LPDS showed an enhanced expression of LDLR and PC3 cells were less sensitive to this effect. HP LNCaP cells were the most affected by lipoprotein deprivation however this effect diminished 72 hours after treatment. The bands profile for SRBI consisted of a 65 kDa predominant band and a 40 kDa band in both LP/HP LNCaP cells. In PC3 cells main band was located in 65 kDa and accessory band in 30kDa. The basal levels of the 65kDa band were higher in HP than in LP LNCaP or PC3 cells and zoledronate therapy caused a dose- dependent induction in HP LNCaP and dose-dependent reduction in PC3 cells, LP LNCaP cells were resistant to the treatment. LPDS induced SRBI levels in all cell lines inverting the effect caused by zoledronate in HP LNCaP cells in complete culture medium and at high doses (100μM) a complete inhibition of SRBI protein was found. Low molecular weight bands changed in the same way as the 65 kDa band. Conclusions: LDL-R and SRBI have been isolated in prostate cancer cell lines. Based on previous cell growth studies, the lipid transporters profile might be significantly involved in the resistance to zoledronate therapy. Lipoprotein regulation pathways should be considered in the therapy of metastatic prostate cancer. No significant financial relationships to disclose.

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