title: Evaluation of Ki67, p53 and angiogenesis in patients enrolled in a randomized study of neoadjuvant chemotherapy with or without cystectomy: a Southwest Oncology Group Study.
abstract: In this prospective biomarker study, we evaluated the prognostic significance of Ki67, p53 and angiogenesis in patients with locally advanced bladder cancer. The patients were volunteers from a Southwest Oncology Group trial of locally advanced bladder cancer who were randomized to treatment with neoadjuvant chemotherapy plus cystectomy or cystectomy alone. Tissue specimens were obtained prior to neoadjuvant chemotherapy from 42 patients randomized to receive the combination-treatment arm and 52 randomized to cystectomy alone. The statistical power of the study was quite limited by the small sample size. The biomarkers were assayed by immunohistochemistry. Angiogenesis was determined using anti-CD34 immunostaining. Patients whose tumors had increased Ki67 expression had better progression-free survival that was marginally significant, p=0.063. The median survival in those with higher Ki67 expression was 73 months, and in those with lower expression was 38 months. However, this did not achieve statistical significance, p=0.25. There was a suggestion of worse survival among patients whose tumors exhibited altered p53 staining [hazard ratio (HR) = 1.48; p=0.15], but there was no difference in progression-free survival (HR=1.02; p=0.93). The enumeration of tumor microvessels did not provide prognostic information.
authors.affiliation: The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA. hbgrossman@mdanderson.org
authors.forename: H Barton
authors.initials: HB
authors.lastname: Grossman
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Tangen
authors.forename: Carlos
authors.initials: C
authors.lastname: Cordon-Cardo
authors.forename: Richard
authors.initials: R
authors.lastname: Cote
authors.forename: Frederic M
authors.initials: FM
authors.lastname: Waldman
authors.forename: Ralph W
authors.initials: RW
authors.lastname: De Vere White
authors.forename: Anand B
authors.initials: AB
authors.lastname: Karnad
authors.forename: Michael
authors.initials: M
authors.lastname: Glode
authors.forename: E David
authors.initials: ED
authors.lastname: Crawford
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000096:biosynthesis; D014408:Biomarkers, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009389:Neovascularization, Pathologic; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53