Microtubule-organizing center-mediated structural atypia in low- and high-grade urothelial carcinoma.
Microtubule-organizing center-mediated structural atypia in low- and high-grade urothelial carcinoma.
复制标题
低级别和高级别尿路上皮癌中微管组织中心介导的结构异型性。
DOI：
10.1007/s00428-020-02895-5
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发表时间：
2020
期刊：
影响因子：
3.5
通讯作者：
Kojima F.
中科院分区：
文献类型：
--
作者：
Murata SI;Kuroda M;Kawamura N;Warigaya K;Musangile FY;Matsuzaki I;Kojima F.
尿路上皮癌（UC）分为低度（LG-UC）和高度（HG-UC）两种亚型，具有不同的病理和临床表现。LG-UC和HG-UC根据病理学发现的细胞和结构特征进行分类。负责维持结构性细胞分裂的机制，如核极性的扰动，仍然不清楚。在这项研究中，我们研究了微管组织中心（MTOC）介导的核极性在UC亚型。我们对6例正常尿路上皮（NU）、10例LG-UC和10例HG-UC进行了MTOC标记物γ-微管蛋白和细胞边界标记物E-cadherin的双重免疫荧光染色。使用与细胞核和表面-基底轴的空间关系评估每例超过100个细胞中γ-微管蛋白表达点的数量和位置。在正常细胞和肿瘤细胞中发现1个γ-微管蛋白点，在NU细胞、LG-UC细胞和HG-UC细胞中发现2个以上的γ-微管蛋白点分别为4.6%、6.1%和9.8%。只有1.2%的HG-UC细胞有3个以上的γ-微管蛋白点。77.4%的正常尿路上皮细胞、63.8%的LG-UC细胞和39.2%的HG-UC细胞中发现γ-微管蛋白的表面侧定位，而22.6%的正常尿路上皮细胞、36.1%的LG-UC细胞和60.8%的HG-UC细胞中发现γ-微管蛋白的异常侧向和基底侧定位。我们的结论是，UC病例中MTOC的数量和位置畸变与细胞和结构异常以及细胞增殖异常密切相关。
Urothelial carcinoma (UC) comprises two subtypes, low grade (LG-UC) and high grade (HG-UC), with different pathological and clinical behavior. LG-UC and HG-UC are classified based on cellular and structural atypia of pathological findings. The mechanisms responsible for maintaining structural atypia, such as the disturbance of nuclear polarity, remain unclear. In this study, we studied microtubule-organizing center (MTOC)-mediated nuclear polarity in UC subtypes. We evaluated six cases with normal urothelium (NU), 10 LG-UC cases, and 10 HG-UC cases by double immunofluorescence staining of γ-tubulin as a marker of MTOC and E-cadherin as a marker of each cell border. The number and position of γ-tubulin dots of expression in more than 100 cells per case were assessed using the spatial relationship with the nucleus and surface-basal axis. We found one γ-tubulin dot in most normal and tumor cells, and more than two γ-tubulin dots in 4.6% of NU cells, 6.1% of LG-UC cells, and 9.8% of HG-UC cells. More than three γ-tubulin dots were found only in 1.2% of HG-UC cells. Surface side positioning of γ-tubulin was found in 77.4% of normal urothelial cells, 63.8% of LG-UC cells, and 39.2% of HG-UC cells, whereas aberrant lateral and basal side positioning of γ-tubulin was found in 22.6% of normal urothelial cells, 36.1% of LG-UC cells, and 60.8% of HG-UC cells. We concluded that numerical and positional aberrations of MTOC in UC cases were strongly correlated with both cellular and structural atypia as well as abnormal cell proliferation.