Baak J P, Ladekarl M, Sørensen F B
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
Hum Pathol. 1994 Jan;25(1):80-5. doi: 10.1016/0046-8177(94)90175-9.
Previous studies have shown that quantitative, histopathologic features obtained from a carefully selected area in the tumor section ("selective" approach) have a strong prognostic value in breast cancer. On the other hand, it was found that mean nuclear volume estimation in the whole area of the tumor section by means of "unbiased" stereologic techniques is of great value in predicting the clinical outcome as well. In the present study the results of the two different (ie, selective and random, systematic) sampling methods in assessing mean nuclear volume have been compared as to their intraobserver and interobserver reproducibility in 22 invasive breast cancer cases. The mean nuclear volume (nuclear vv) was assessed both in the most atypical area (AREA) (selected on morphologic criteria) and in the whole tumor section (TOTAL). Furthermore, the correlation with mean nuclear (profile) area (MNA) was studied. Mean nuclear (profile) area was determined in the AREA only. With bivariate correlation analysis the two sampling methods showed high correlation for the nuclear vv values (range of the correlation coefficient, 0.92 to 0.97). There were no systematic intraobserver differences between the different sampling methods. The results of observer 1 showed higher values, both with the selective and random systematic sampling methods. However, these systematic interobserver differences were small (< 9% of the average value of nuclear vv), much smaller than the variation between the tumors (which was > 60%). The time required for assessments in the AREA was less than that required for the determinations in the TOTAL (average, 10 v 20 minutes) in spite of the similar sample size. This is understandable, as in a sclerotic tumor many fields of vision do not contain cancer nuclei. The time required for MNA determinations in the AREA was longer than for nuclear vv assessments in the AREA (15 v 10 minutes). Nuclear vv and MNA (both assessed in the AREA) were (log distributed) significantly correlated (r = .77). Thus, nuclear vv determination in the AREA is the fastest method, and it is also well reproducible and strongly correlated with nuclear vv assessed in the TOTAL. In invasive breast cancer assessments in the whole tumor section can be used if delineation of the measurement area cannot be done easily. In small areas with a limited number of nuclei (eg, microinvasive parts) MNA can be easier to assess than nuclear vv. Further studies are required to compare and evaluate the prognostic value of nuclear vv and MNA.
以往研究表明，从肿瘤切片中精心挑选的区域获得的定量组织病理学特征（“选择性”方法）对乳腺癌具有很强的预后价值。另一方面，研究发现，通过“无偏倚”立体学技术对肿瘤切片整个区域进行平均核体积估计，在预测临床结果方面也具有重要价值。在本研究中，比较了两种不同（即选择性和随机、系统性）抽样方法在评估平均核体积时的观察者内和观察者间的可重复性，研究对象为22例浸润性乳腺癌病例。在最不典型区域（根据形态学标准选择）和整个肿瘤切片中均评估了平均核体积（核vv）。此外，还研究了其与平均核（轮廓）面积（MNA）的相关性。仅在最不典型区域测定了平均核（轮廓）面积。通过双变量相关性分析，两种抽样方法的核vv值显示出高度相关性（相关系数范围为0.92至0.97）。不同抽样方法之间在观察者内没有系统性差异。观察者1的结果在选择性和随机系统性抽样方法下均显示出较高的值。然而，这些观察者间的系统性差异较小（<核vv平均值的9%），远小于肿瘤之间的差异（>60%）。尽管样本量相似，但最不典型区域的评估所需时间少于整个肿瘤切片的测定所需时间（平均分别为10分钟和20分钟）。这是可以理解的，因为在硬化性肿瘤中，许多视野中不包含癌细胞核。最不典型区域的MNA测定所需时间比该区域的核vv评估所需时间长（分别为15分钟和10分钟）。核vv和MNA（均在最不典型区域评估）呈（对数分布）显著相关（r = 0.77）。因此，在最不典型区域测定核vv是最快的方法，并且具有良好的可重复性，且与在整个肿瘤切片中评估的核vv高度相关。在浸润性乳腺癌评估中，如果难以轻松划定测量区域，则可以使用整个肿瘤切片。在核数量有限的小区域（如微浸润部分），MNA可能比核vv更容易评估。需要进一步研究以比较和评估核vv和MNA的预后价值。
