title: Cell cycle inhibitors and outcome after radiotherapy in bladder cancer patients.
abstract: The aim of this study was to correlate the expression of cell cycle inhibitors with outcome of patients with muscle-invasive bladder cancer treated with preoperative radiotherapy (46 Gy/4-5 weeks or 20 Gy/1 week) and cystectomy. Patients with pT3b (n = 42) or pT0 (n = 17) were included in the study. Expression of p16INK4a and p27KIP1 was assessed immunohistochemically in pre-radiotherapy biopsies and cystectomy specimens. Previously reported results of p21CP1 expression were also included. No difference in pretreatment protein expression was found between patients with pT0 and pT3b. Expression of p21CIP1 and p27KIP1 was lower in cystectomy specimens than in pretreatment biopsies. None of the proteins showed significant impact on survival when analysed separately. However, patients with tumours showing > 50% expression of p16INK4a, p21CIP1, or p27KIP1 displayed poorer cancer-specific survival rates compared with the remaining patients (p = 0.025). This effect was more pronounced in patients receiving 46 Gy than in those receiving 20 Gy. In conclusion, low expression of cell cycle inhibitors is related to favourable survival after pre-cystectomy radiotherapy.
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo. ranveiro@ulrik.uio.no
authors.forename: Ranveig
authors.initials: R
authors.lastname: Røtterud
authors.forename: Erik O
authors.initials: EO
authors.lastname: Pettersen
authors.forename: Aasmund
authors.initials: A
authors.lastname: Berner
authors.forename: Ruth
authors.initials: R
authors.lastname: Holm
authors.forename: Dag Rune
authors.initials: DR
authors.lastname: Olsen
authors.forename: Sophie D
authors.initials: SD
authors.lastname: Fosså
mesh_terms: D002295:Carcinoma, Transitional Cell / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000032:analysis*; D003404:Creatinine / Q000097:blood; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000032:analysis*; D015653:Cystectomy; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D015993:Life Tables; D009130:Muscle, Smooth / Q000473:pathology; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis*; D011836:Radiation Tolerance; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000032:analysis*; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery
chemical_list: C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D006454:Hemoglobins; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003404:Creatinine