Proliferative status is a risk index for recurrence in primary superficial (pTa/T1) low-grade urothelial bladder carcinoma

Abstract

再発危険因子検索のため, pTa33例とpTl46例の膀胱癌患者にKi-67, c-erbB-2, p53と多薬剤耐性蛋白(MRP)を免疫組織化学的に検討した.その結果, pTl, 広基性, 腫瘍径の大きな腫瘍(>3cm)の再発率は高かった.また, Ki-67, c-erbB-2, p53の過剰発現症例の再発率は, 有意に高かったが, MRP発現と再発とは関連がなかった.多変量解析では, 腫瘍径の大きな腫瘍とKi-67高発現が再発の独立した予後因子であった.腫瘍径が1cm未満の症例の再発は, Ki-67およびp53過剰発現が関連した.Ki-67高発現により, grage2.pTlおよび単発腫瘍において, 再発の高い症例を識別できた.このことより, 増殖関連蛋白を臨床病理因子に加えることにより, 重要な予後を規定する情報となることを示しており, Ki-67高発現が信頼しうる再発予後因子であると考えられた

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.