Role of Tumor Suppressor and Angiogenesis Markers in Prediction of Recurrence of Non Muscle Invasive Bladder Cancer

Abstract

Non muscle invasive bladder cancers recur frequently and identification of biomarkers for predicting recurrence are necessary. The present study evaluated the individual and synergistic effects of tumor suppressor (p53/p21waf1) and angiogenesis [vascular endothelial growth factor (VEGF)/endoglin (CD105)] markers. The study included 90 cases of non muscle invasive bladder cancer. Cell spots were stained with primary antibodies and Flourescein isothiocyanate (FITC). Slides were observed under confocal laser scanning microscope for protein expression. The association between the markers individually and synergistically with recurrence were assessed by a χ2 and Fisher's Exact test. Survival analysis was performed to predict recurrence and test for significant difference in recurrence free survival probability. Recurrence [overall:39(43.3%) and low grade(LG):26(54.2%)] was significant with p53 and VEGF expression and the profiles p53/VEGF, p53/CD105, VEGF/CD105, p53/p21/CD105, p53/VEGF/CD105 and all four were significantly associated with recurrence in both groups. In the multivariable model the [HR(95%CI),p: overall and LG] profiles p21/VEGF [2.195(1.052-4.582),0.036; 3.425(1.332-8.811),0.011], VEGF/CD105[2.624(1.274-5.403),0.009 and 3.380(1.348-8.472),0.009], p53/p21/CD105 [2.000(0.993-4.027),0.052 and 2.539(1.047-6.157),0.039], p53/VEGF/CD105 [2.360(1.148-4.849),0.020 and 2.738(1.104-6.788),0.030], p21/VEGF/CD105 [2.611(1.189-5.731),0.017 and 3.946(1.530-10.182),0.005] and all four [2.382(1.021-5.556),0.045 and 3.572(1.287-9.911),0.014] significantly predicted the recurrence along with significant log rank. In the pTa subset (n = 33) the profiles p53/p21, p53/CD105, p21/VEGF, VEGF/CD105, p53/VEGF/CD105, p53/p21/CD105 and p21/VEGF/CD105, significantly predicted hazard for recurrence. The present study emphasizes an underlying association between tumor suppressor (p21waf1) and angiogenesis (VEGF/CD105) biomarkers. In addition combination profiles appeared to indicate an aggressive nature with high propensity for recurrence in LG and pTa tumours.

TSP-1-1223 A/G Polymorphism as a Potential Predictor of the Recurrence Risk of Bladder Cancer in a Chinese Population

“…The expression level of TSP-1 mRNA was the lowest in individuals with homozygous G allele. As such, the shorter time-to-recurrence in patients with bladder cancer exhibiting a G allele may be attributed to a decreased TSP-1 expression, which has been associated with an increased risk of disease recurrence and a decreased overall survival by promoting tumour neovascularization [17, 18, 34]. Our results partly supported our hypothesis; however, further functional experiments should be conducted to validate the specific mechanism.…”

“…Angiogenesis is associated with an increased recurrence risk of bladder cancer [34]. The downregulation of TSP-1 in bladder cancer is considered as a primary factor contributing to specific changes, for instance, from an antiangiogenic to an angiogenic phenotype during cancer development and recurrence [17, 18, 33].…”

BASIC SCIENCE HIF-1, GLUT1, endoglin, and BIRC5 expression in urine samples obtained from patients with bladder malignancies – after photodynamic diagnosis (PDD)

“…Endoglin is an independent prognostic factor and it correlates with metastatic disease and poor survival. These results were presented by Santos et al [20] and Agrawal et al [21]. Also, an elevated level of endoglin in blood serum, as well as in urine, can be typical of gastric (Salvensen et al [22]) and endometrial cancers (Nikiteas et al [23]).…”

Endoglin expression in upper urinary tract urothelial carcinoma is associated with intravesical recurrence after radical nephroureterectomy

“…The expression of endoglin has been previously studied in bladder cancer. 17,18 Santos et al reported that the presence of angiogenesis in tumor urothelium, which was evaluated as the immunoexpression of endoglin, was significantly associated with disease recurrence in patients with pTa and pT1 bladder cancer who underwent transurethral resection of the bladder tumor. Agrawal et al reported that the ratio of p53/endoglin expression was associated with bladder recurrence in pTa and pT1 bladder cancer, but that endoglin alone was not associated with bladder recurrence.…”

“…Agrawal et al reported that the ratio of p53/endoglin expression was associated with bladder recurrence in pTa and pT1 bladder cancer, but that endoglin alone was not associated with bladder recurrence. 17 MVD in UTUC was also studied through the immunoexpression of CD34, but the results were controversial. 19 MVD assessed by immunoexpression of CD34 was associated with CSS in 55 patients with UTUC.…”