title: Proliferative status is a risk index for recurrence in primary superficial (pTa/T1) low-grade urothelial bladder carcinoma.
abstract: The current clinicopathologic study for evaluation of superficial bladder cancer still has limitations in predicting the true behavior of recurrence. To determine the high-risk recurrence factors, we studied the influence of Ki-67, c-erbB-2, p53 and multidrug resistance-associated protein (MRP) expression. Samples were obtained from 33 pTa and 46pT1 diagnosed bladder cancer patients with a mean follow-up of 48.7 +/- 30.6 months. The contingency table method, Kaplan-Meier curve and multivariate analysis were used to evaluate the association among the immunohistochemical factors expression, clinicopathologic parameters with tumor recurrence. Stage pT1 tumors, sessile tumors and large tumors (> 3 cm) showed a significantly high recurrence rate (p = 0.0158, p = 0.0162, p = 0.0001 respectively). Tumors with overexpression of Ki-67, c-erbB-2 and p53 were more likely to recur (p = 0.0035, p = 0.0027, p = 0.0076 respectively), MRP expression was not associated with recurrence. Multivariate analysis showed that large tumors and high Ki-67 expression were independent indicators of recurrence. On the other hand, in tumors less than 1 cm, recurrence was significantly correlated with overexpression of Ki-67 and p53. High Ki-67 expression could discriminate higher recurrence cases in grade 2, pT1 and single tumors. The c-erbB-2 overexpression was more frequently associated with recurrence in sessile tumors, large tumors, multiple and grade 1 tumors. The p53 overexpression also predicted a higher risk of recurrence in pTa tumors. These data demonstrated that the use of proliferative related proteins yields significant prognostic information in addition to clinicopathological factors, high Ki-67 expression is a reliable indicator of recurrence. A combination rather than any factor alone could more accurately predict tumor recurrence.
authors.affiliation: Department of Urology, Faculty of Medicine, Mie University.
authors.forename: Jing-Shi
authors.initials: JS
authors.lastname: Su
authors.forename: Kiminobu
authors.initials: K
authors.lastname: Arima
authors.forename: Mariko
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Omar E
authors.initials: OE
authors.lastname: Franco
authors.forename: Makoto
authors.initials: M
authors.lastname: Yanagawa
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sugimura
authors.forename: Juichi
authors.initials: J
authors.lastname: Kawamura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology*; D009367:Neoplasm Staging; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53