Kay E W, Walsh C J, Cassidy M, Curran B, Leader M
Department of Pathology, Royal College of Surgeons, Ireland.
J Clin Pathol. 1994 Sep;47(9):816-22. doi: 10.1136/jcp.47.9.816.
To assess the consistency and reproducibility of assessment of c-erbB-2 immunostaining, and to examine some of the problems relating to inter- and intraobserver variability in the documentation of positive staining; to profile the spectrum of cytoplasmic and membranous staining in a wide range of tumour types.
A total of 283 neoplasms were examined for immunohistochemical expression of the c-erbB-2 oncoprotein. Three independent observers were required to assess intensity both of membrane and cytoplasmic staining on a three point and then a four point scale. Extent of positive staining was also assessed on a two point scale. A minimum of two weeks elapsed between assessments using the differing scales.
Positive membrane staining was documented by one or more observers in 16.6% of tumours examined. This positivity was largely restricted to bladder, renal, and breast tumours. The overall level of disagreement as to the presence or absence of membranous staining was 11.3%. Cytoplasmic staining was identified in 55.5% of tumours studied. The level of disagreement as to the presence or absence of cytoplasmic staining was 26.5%.
Intraobserver variability was minimal, indicating that each pathologist was adhering to internal reproducible standards. Interobserver variability was greater, indicating that the interpretation of c-erbB-2 immunostaining may require set guidelines. It is suggested that assessment should be referenced to a standard positive control, that a three tier system for grading of intensity and a two tier system for grading of extent should be adopted, and that the evaluation should be agreed by at least two pathologists. The presence of cytoplasmic staining should continue to be routinely recorded until its biological role and clinical implications are fully understood.
评估c-erbB-2免疫染色评估的一致性和可重复性，并研究阳性染色记录中与观察者间和观察者内变异性相关的一些问题；描绘多种肿瘤类型中细胞质和细胞膜染色的谱系。
共检查了283个肿瘤的c-erbB-2癌蛋白的免疫组化表达。要求三名独立观察者在三点然后四点量表上评估细胞膜和细胞质染色的强度。阳性染色范围也在两点量表上进行评估。使用不同量表进行评估之间至少间隔两周。
在检查的肿瘤中，16.6%的肿瘤有一名或多名观察者记录到阳性细胞膜染色。这种阳性主要局限于膀胱、肾脏和乳腺肿瘤。关于细胞膜染色是否存在的总体分歧水平为11.3%。在研究的肿瘤中，55.5%发现有细胞质染色。关于细胞质染色是否存在的分歧水平为26.5%。
观察者内变异性最小，表明每位病理学家都遵循内部可重复的标准。观察者间变异性更大，表明c-erbB-2免疫染色的解释可能需要设定指导原则。建议评估应参考标准阳性对照，采用强度分级的三级系统和范围分级的二级系统，并且评估应由至少两名病理学家达成一致。在细胞质染色的生物学作用和临床意义被充分理解之前，应继续常规记录其存在情况。
