title: 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.
authors.affiliation: Institute of Pathology, Indian Council of Medical Research, Post Box no. 4909, Safdarjung Hospital Campus, New Delhi 110029, India.
authors.forename: Usha
authors.initials: U
authors.lastname: Agrawal
authors.forename: Ashwani K
authors.initials: AK
authors.lastname: Mishra
authors.forename: Payal
authors.initials: P
authors.lastname: Salgia
authors.forename: Saurabh
authors.initials: S
authors.lastname: Verma
authors.forename: Nayan K
authors.initials: NK
authors.lastname: Mohanty
authors.forename: Sunita
authors.initials: S
authors.lastname: Saxena
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis / Q000096:biosynthesis; D000071063:Endoglin; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000032:analysis / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A