Tsuda Hitoshi, Sasano Hironobu, Akiyama Futoshi, Kurosumi Masafumi, Hasegawa Tadashi, Osamura R Yoshiyuki, Sakamoto Goi
Second Department of Pathology, National Defense Medical College, Tokorozawa, Japan.
Pathol Int. 2002 Feb;52(2):126-34. doi: 10.1046/j.1440-1827.2002.01327.x.
To examine interobserver reproducibility in the judgments of HER-2/neu (c-erbB-2) oncoprotein expression, HER-2/neu expression was scored immunohistochemically. A total of 106 breast carcinomas were independently scored by five or six pathologists, using four commercially available anti-bodies (HercepTest, Nichirei polyclonal antibody, CB11 and TAB250). Two systems were used for the evaluation. In the Dako system, the intensity of membrane staining was primarily evaluated whereas in the Tohoku system, the area of the membrane-staining-positive cells was primarily evaluated. All four antibodies gave excellent concordance rates among the pathologists' judgments of the scores. Using the HercepTest and Nichirei polyclonal antibody, dividing the cases into two groups designated score 3+ and score 0/1+/2+ achieved a higher percentage of concordant cases than division into groups designated score 2+/3+ and score 0/1+. Using the HercepTest, the Dako system tended to achieve higher concordance than the Tohoku system. Conversely, CB11 and TAB250 showed similar concordance rates under both the Dako and the Tohoku systems, regardless of how the cases were divided. High interobserver agreement levels were achieved only when HER-2/neu overexpression was defined as a score of 3+, using any of the antibodies; these were similar between the Dako system and the Tohoku system. Positivity by TAB250 was lower than that by CB11. Using the HercepTest and Nichirei polyclonal antibody, cases with a score of 3+ almost always achieved complete interobserver agreement and showed HER-2/neu gene amplification. Conversely, cases with a score of 2+ achieved a low percentage of interobserver agreement and showed no gene amplification. Because judgment of a case as score 2+ was not very reproducible, and a score of 3+ was of biological significance and had high interobserver reproducibility, we suggest that only a score of 3+ be considered as overexpression. When cases of score 2+ are entered into a protocol, evaluation should be given by multiple observers and/or by using other tests such as fluorescence in situ hybridization.
为研究HER-2/neu（c-erbB-2）癌蛋白表达判断中观察者间的可重复性，采用免疫组织化学方法对HER-2/neu表达进行评分。106例乳腺癌由五或六位病理学家独立评分，使用四种市售抗体（赫赛汀检测试剂、日水制果多克隆抗体、CB11和TAB250）。采用两种系统进行评估。在达科系统中，主要评估膜染色强度，而在东北系统中，主要评估膜染色阳性细胞的面积。所有四种抗体在病理学家对评分的判断中均具有出色的一致性率。使用赫赛汀检测试剂和日水制果多克隆抗体，将病例分为3+评分组和0/1+/2+评分组比分为2+/3+评分组和0/1+评分组获得更高比例的一致病例。使用赫赛汀检测试剂时，达科系统往往比东北系统获得更高的一致性。相反，无论病例如何分组，CB11和TAB250在达科系统和东北系统下的一致性率相似。仅当使用任何一种抗体将HER-2/neu过表达定义为3+评分时，才能获得较高的观察者间一致性水平；达科系统和东北系统之间相似。TAB250的阳性率低于CB11。使用赫赛汀检测试剂和日水制果多克隆抗体时，3+评分的病例几乎总是实现完全观察者间一致，并显示HER-2/neu基因扩增。相反，2+评分的病例观察者间一致率较低，且未显示基因扩增。由于将病例判断为2+评分的可重复性不太好，而3+评分具有生物学意义且观察者间可重复性高，我们建议仅将3+评分视为过表达。当将2+评分的病例纳入方案时，应由多名观察者和/或使用其他检测方法如荧光原位杂交进行评估。
