Sabo Edmond, Gibrat Myriam, Sova Yanina, Stein Avi, Resnick Murray B
Department of Pathology, Carmel Medical Center, 7 Michal Street, Haifa, Israel, 34362.
Anal Quant Cytol Histol. 2003 Feb;25(1):53-62.
To evaluate the role of the novel histomorphometric variables of pleomorphism, orientation and variability of spatial cytologic organization to objectively quantify histopathologic grade in urothelial carcinoma.
As a validation model, we chose 51 papillary urothelial carcinomas. Thirty-six (70%) were low and 15 (29%) high grade tumors (World Health Organization grading system). Thirty-one cases (61%) were noninvasive, 12 (23%) exhibited lamina propria invasion, and 8 (16%) invaded the deep smooth muscle. Histomorphometric measurements were performed on noninvasive areas only. Pleomorphism was characterized by the anisokaryosis index (AIX), based on the autocorrelation function applied to classic nuclear shape descriptors. Additional indices of pleomorphism included standard deviations (sd) and coefficients of variation of these shape descriptors. Loss of polarity was assessed by the orientation index (ORX), based on Fourier transformation. Intraepithelial nuclear spatial distribution index (NSDX) was also computed.
Low grade tumors exhibited less pleomorphism, higher orientation indices and a more homogeneous spatial distribution than did high grade tumors (area-AIX: P = .004, ORX: P < .0001, NSDX: P = .001). Multivariate analysis revealed the significant discriminators of grade to be nuclear size and orientation (size: max-diam, P < .0001; width: P < .0001; orientation: ORX: P < .0001). A discriminant score combining these independent variables distinguished between low and high grades in 98% of cases. The method was successfully validated using a testing sample of 40 new patients (accuracy, 94%). Lamina propria invasion was independently predicted by nuclear pleomorphism (width-sd: P = .0001, sensitivity = 64%, specificity = 91%). Muscle invasion was independently predicted by nuclear area (P < .0001) and pleomorphism (area-sd: P < .0001, max-diam-sd: P < .0001, width-AIX: P < .0001, sensitivity = 87%, specificity = 100%).
These novel morphometric methods may serve as more objective methods of histopathologic grading and may contribute to the development of automated systems for quantitative grading of stratified and transitional epithelial neoplasms.
评估多形性、空间细胞学组织的取向和变异性这些新的组织形态计量学变量在客观量化尿路上皮癌组织病理学分级中的作用。
作为验证模型，我们选取了51例乳头状尿路上皮癌。其中36例（70%）为低级别肿瘤，15例（29%）为高级别肿瘤（世界卫生组织分级系统）。31例（61%）为非浸润性，12例（23%）表现为固有层浸润，8例（16%）侵犯深层平滑肌。仅对非浸润区域进行组织形态计量学测量。多形性通过基于应用于经典核形状描述符的自相关函数的核大小不等指数（AIX）来表征。多形性的其他指标包括这些形状描述符的标准差（sd）和变异系数。极性丧失通过基于傅里叶变换的取向指数（ORX）进行评估。还计算了上皮内核空间分布指数（NSDX）。
与高级别肿瘤相比，低级别肿瘤表现出更少的多形性、更高的取向指数和更均匀的空间分布（面积 - AIX：P = 0.004，ORX：P < 0.0001，NSDX：P = 0.001）。多变量分析显示，分级的显著判别因素为核大小和取向（大小：最大直径，P < 0.0001；宽度：P < 0.0001；取向：ORX：P < 0.0001）。结合这些独立变量的判别分数在98%的病例中区分了低级别和高级别。使用40例新患者的测试样本成功验证了该方法（准确率94%）。固有层浸润由核多形性独立预测（宽度 - sd：P = 0.0001，敏感性 = 64%，特异性 = 91%）。肌肉浸润由核面积（P < 0.0001）和多形性独立预测（面积 - sd：P < 0.0001，最大直径 - sd：P < 0.0001，宽度 - AIX：P < 0.0001，敏感性 = 87%，特异性 = 100%）。
这些新的形态计量学方法可作为更客观的组织病理学分级方法，并可能有助于开发用于分层和移行上皮肿瘤定量分级的自动化系统。
