Bollmann Daniel, Bollmann Magdolna, Bankfalvi Agnes, Heller Hildegard, Bollmann Reinhard, Pajor Gabor, Hildenbrand Ralf
Institute of Pathology, Bonn-Duisdorf, Germany.
Oncol Rep. 2009 Jan;21(1):39-47.
The present study aimed to assess whether patients with bladder urothelial tumours can be more objectively stratified into low- and high-risk groups for recurrence and progression using a 2-tired molecular grading scheme, than by subjective histopathological grading alone. Biopsy material from 45 consecutive patients with urothelial bladder neoplasias (2 papillary urothelial neoplasm of low malignant potentials, 18 pTa, 1 pTis, 19 pT1 and 5 pT2) was analysed for immunohistochemical Ki-67 and p53 expression. Labelling indices were assessed by automated cellular image analysis. UroVysion FISH test results were evaluated by automated signal counting, and DNA ploidy of single nuclei preparations were measured by image cytometry. Sixty-nine percent of cases showed >10% Ki-67 LI, 64% had >10% p53 LI, 53% revealed DNA aneuploidy and 56% expressed a high-risk FISH pattern. Based on a combination of single molecular markers, 75% of neoplasias were classified as high molecular grade. Tumour stage and histopathological grade were significantly associated with FISH pattern, DNA ploidy and MIB1 LI. Stage was also related with molecular grade. Clinical outcome showed a significant correlation with MIB1 LI and molecular grade. P53 had neither diagnostic nor prognostic relevance, nor was there any correlation between histological and molecular grade. Our preliminary data strongly suggest that the combination of quantitative biomarkers provides superior and objective prognostic tools in bladder urothelial neoplasias compared to classic clinicopathological features and indices.
本研究旨在评估与单纯依靠主观的组织病理学分级相比，使用双层次分子分级方案是否能更客观地将膀胱尿路上皮肿瘤患者分为复发和进展的低风险组和高风险组。对45例连续性尿路上皮膀胱肿瘤患者（2例低恶性潜能乳头状尿路上皮肿瘤、18例pTa、1例pTis、19例pT1和5例pT2）的活检材料进行免疫组化Ki-67和p53表达分析。通过自动细胞图像分析评估标记指数。通过自动信号计数评估UroVysion FISH检测结果，并通过图像细胞术测量单核制剂的DNA倍体。69%的病例显示Ki-67 LI>10%，64%的病例p53 LI>10%，53%的病例显示DNA非整倍体，56%的病例表达高风险FISH模式。基于单一分子标志物的组合，75%的肿瘤被归类为高分子级别。肿瘤分期和组织病理学分级与FISH模式、DNA倍体和MIB1 LI显著相关。分期也与分子级别相关。临床结果与MIB1 LI和分子级别显著相关。P53既无诊断相关性也无预后相关性，组织学分级与分子分级之间也无相关性。我们的初步数据强烈表明，与经典的临床病理特征和指标相比，定量生物标志物的组合为膀胱尿路上皮肿瘤提供了更优越和客观的预后工具。
