Department of Pathology, HELIOS Clinic Bad Saarow, Bad Saarow, Germany.
J Clin Pathol. 2012 Aug;65(8):715-20. doi: 10.1136/jclinpath-2011-200532. Epub 2012 May 3.
To systematically compare different approaches for evaluating mucosal proliferative activity regarding their diagnostic role for delineating flat lesions of the bladder mucosa.
32 carcinoma in situ (CIS) and 31 flat non-CIS conditions (low-grade dysplasia and reactive atypia) of the bladder mucosa were assessed by two independent pathologists in two rounds in terms of their proliferative activity assessed by the mitotic counts on H&E-stained sections (mitoses per mm(2)) and immunohistochemically using the MIB-1 antibody and the mitosis marker phosphohistone H3 (PHH3). Two different approaches for immunoscoring (percentage of stained nuclei vs dichotomised height of mucosal staining considering lower half vs full-thickness marker expression) were applied. κ statistics were used to evaluate interobserver and intraobserver reproducibility.
Scoring the percentage of Ki67 expressing cell nuclei seems to be superior to dichotomisation of the height of mucosal staining as well as to PHH3 immunostaining and conventional mitotic counts in terms of delineating CIS from flat non-CIS conditions. This approach shows substantial (κ=0.62-0.65; p<0.001) interobserver and substantial to almost perfect (κ=0.67-0.83; p<0.001) intraobserver reproducibility.
The MIB-1 antibody is a useful adjunct in the differential diagnosis of conventionally challenging flat lesions of the bladder mucosa. In particular, 16% or more Ki67 positive cell nuclei favours CIS over flat non-CIS conditions, whereas 15% or less Ki67 positive cell nuclei is supportive of non-CIS conditions. However, due to some important limitations of MIB-1 staining, the MIB-1 antibody should be used as a component of a panel.
系统比较不同的评估方法在评估膀胱黏膜平坦病变的诊断作用方面的差异，这些方法都是基于评估组织的有丝分裂计数。
32 例原位癌（CIS）和 31 例膀胱黏膜平坦非 CIS 病变（低级别上皮内瘤变和反应性不典型增生）由两位独立的病理学家在两轮评估中，通过对 H&E 染色切片（每平方毫米有丝分裂数）进行的有丝分裂计数和使用 MIB-1 抗体和有丝分裂标志物磷酸组蛋白 H3（PHH3）进行的免疫组化染色评估其增殖活性。采用两种不同的免疫组化评分方法（染色细胞核的百分比与考虑下半部分和全层标记物表达的黏膜染色高度的二分法）。使用 κ 统计来评估观察者间和观察者内的可重复性。
在区分 CIS 与平坦非 CIS 病变方面，Ki67 表达细胞核的百分比评分似乎优于黏膜染色高度的二分法以及 PHH3 免疫染色和传统有丝分裂计数。这种方法显示出明显的（κ=0.62-0.65；p<0.001）观察者间和明显到几乎完美的（κ=0.67-0.83；p<0.001）观察者内可重复性。
MIB-1 抗体是鉴别具有挑战性的传统膀胱黏膜平坦病变的有用辅助方法。特别是，16%或更多的 Ki67 阳性细胞核更倾向于 CIS 而非平坦非 CIS 病变，而 15%或更少的 Ki67 阳性细胞核支持非 CIS 病变。然而，由于 MIB-1 染色存在一些重要的局限性，MIB-1 抗体应作为一个组合的一部分使用。
