Malshy Kamil, Amiel Gilad E, Hershkovitz Dov, Sabo Edmond, Hoffman Azik
Department of Urology, Rambam Health Care Campus, 8 HaAliya HaShniya Street, Haifa 3109601, Israel.
Institute of Pathology, Sourasky Medical Center, Tel Aviv 6997801, Israel.
Diagnostics (Basel). 2022 May 31;12(6):1356. doi: 10.3390/diagnostics12061356.
Objective: Gleason scoring system remains the pathological method of choice for prostate cancer (Pca) grading. However, this method of tumor tissue architectural structure grading is still affected by subjective assessment and might succumb to several disadvantages, mainly inter-observer variability. These limitations might be diminished by determining characteristic cellular heterogeneity parameters which might improve Gleason scoring homogeneity. One of the quantitative tools of tumor assessment is the morphometric characterization of tumor cell nuclei. We aimed to test the relationship between various morphometric measures and the Gleason score assigned to different prostate cancer samples. Materials and Methods: We reviewed 60 prostate biopsy samples performed at a tertiary uro-oncology center. Each slide was assigned a Gleason grade according to the International Society of Urological Pathology contemporary grading system by a single experienced uro-pathologist. Samples were assigned into groups from grades 3 to 5. Next, the samples were digitally scanned (×400 magnification) and sampled on a computer using Image-Pro-Plus software©. Manual segmentation of approximately 100 selected tumor cells per sample was performed, and a computerized measurement of 54 predetermined morphometric properties of each cell nuclei was recorded. These characteristics were used to compare the pathological group grades assigned to each specimen. Results: Initially, of the 54 morphometric parameters evaluated, 38 were predictive of Gleason grade (p < 0.05). On multivariate analysis, 7 independent parameters were found to be discriminative of different Pca grades: minimum radius shape, intensity—minimal gray level, intensity—maximal gray level, character—gray level (green), character—gray level (blue), chromatin color, fractal dimension, and chromatin texture. A formula to predict the presence of Gleason grade 3 vs. grades 4 or 5 was developed (97.2% sensitivity, 100% specificity). Discussion: The suggested morphometry method based on seven selected parameters is highly sensitive and specific in predicting Gleason score ≥ 4. Since discriminating Gleason score 3 from ≥4 is essential for proper treatment selection, this method might be beneficial in addition to standard pathological tissue analysis in reducing variability among pathologists.
Gleason评分系统仍然是前列腺癌（Pca）分级的首选病理方法。然而，这种肿瘤组织结构分级方法仍受主观评估影响，可能存在一些缺点，主要是观察者间差异。通过确定特征性细胞异质性参数可能会减少这些局限性，这可能会提高Gleason评分的同质性。肿瘤评估的定量工具之一是肿瘤细胞核的形态计量学特征。我们旨在测试各种形态计量学测量与分配给不同前列腺癌样本的Gleason评分之间的关系。
我们回顾了在一家三级泌尿肿瘤中心进行的60例前列腺活检样本。由一位经验丰富的泌尿病理学家根据国际泌尿病理学会当代分级系统为每张切片指定Gleason分级。样本被分为3至5级组。接下来，对样本进行数字扫描（×400放大倍数），并使用Image-Pro-Plus软件©在计算机上进行采样。对每个样本中约100个选定的肿瘤细胞进行手动分割，并记录每个细胞核54个预定形态计量学特性的计算机测量值。这些特征用于比较分配给每个标本的病理组分级。
最初，在评估的54个形态计量学参数中，38个可预测Gleason分级（p < 0.05）。多变量分析发现，7个独立参数可区分不同的Pca分级：最小半径形状、强度—最小灰度级、强度—最大灰度级、特征—灰度级（绿色）、特征—灰度级（蓝色）、染色质颜色、分形维数和染色质纹理。开发了一个预测Gleason 3级与4级或5级存在的公式（敏感性97.2%，特异性100%）。
基于七个选定参数的建议形态计量学方法在预测Gleason评分≥4时具有高度敏感性和特异性。由于区分Gleason 3分与≥4分对于正确选择治疗方法至关重要，因此除了标准病理组织分析外，该方法可能有助于减少病理学家之间的差异。
