El-Gendi Saba, Abu-Sheasha Ghada
Department of Pathology, Faculty of Medicine, University of Alexandria, 29 Fawzy Moaaz Street, Smouha, Alexandria, 21646, Egypt.
Department of Biomedical Informatics and Medical Statistics, Medical Research Institute, University of Alexandria, Alexandria, Egypt.
Pathol Oncol Res. 2018 Apr;24(2):309-322. doi: 10.1007/s12253-017-0250-2. Epub 2017 May 9.
Deregulation of the cell cycle regulating genes is common in urothelial bladder carcinoma (UBC). We aimed to examine the prognostic significance of ki-67, p53, p63 and cyclinD1expression in UBC and to identify optimal cut-off points to help identifying patients at high risk of tumor recurrence. We evaluated the immunohistochemical expression of ki-67, p53, p63 and cyclinD1 in 100 UBCs. The conventional and the classification and regression trees-guided (CART-guided) methods were utilized to determine the independent predictors of tumor recurrence. The p53 and Ki-67 expression didn't associate significantly with tumor recurrence.p63 and cyclinD1 exhibited significant hazard ratios. Using CART, no recurrence was observed when p63 was ≥87.5%. The recurrence incidence increased and the disease free survival (DFS) time shortened as the p63 decreased. CyclinD1 associated significantly with tumor recurrence only if p63 was <35%. Using the CART cut-off values¬, cases were categorized into three groups; (groups I: p63 ≥ 35%, II: p63 < 35% and cyclinD1 < 10% and III: p63 < 35% and cyclinD1 ≥ 10%). Group I patients revealed the least incidence of recurrence at the longest DFS. Group III had the worst prognosis followed by Group II. p63 represents a surrogant biomarker to predict UBC recurrence.CyclinD1 can be used only when p63 is <35%. CART proved helpful with data among which the number of cases with positive outcomes is too small relative to the number of studied predictors. Large cohort studies for ki-67 and p53 are recommended to be performed with standardized criteria as regards patients' characteristics, cut-off values, and follow-up time.
细胞周期调节基因的失调在膀胱尿路上皮癌（UBC）中很常见。我们旨在研究ki-67、p53、p63和细胞周期蛋白D1表达在UBC中的预后意义，并确定最佳切点以帮助识别肿瘤复发高危患者。我们评估了100例UBC中ki-67、p53、p63和细胞周期蛋白D1的免疫组化表达。采用传统方法和分类与回归树引导（CART引导）方法来确定肿瘤复发的独立预测因素。p53和Ki-67表达与肿瘤复发无显著相关性。p63和细胞周期蛋白D1表现出显著的风险比。使用CART分析，当p63≥87.5%时未观察到复发。随着p63降低，复发发生率增加，无病生存期（DFS）缩短。仅当p63<35%时，细胞周期蛋白D1与肿瘤复发显著相关。使用CART切点值，病例被分为三组；（I组：p63≥35%，II组：p63<35%且细胞周期蛋白D1<10%，III组：p63<35%且细胞周期蛋白D1≥10%）。I组患者复发率最低，DFS最长。III组预后最差，其次是II组。p63是预测UBC复发的替代生物标志物。仅当p63<35%时可使用细胞周期蛋白D1。CART被证明有助于处理阳性结果病例数相对于研究预测因素数量过少的数据。建议按照患者特征、切点值和随访时间标准化标准对ki-67和p53进行大型队列研究。
