C-ERBB-2 IMMUNOSTAINING - PROBLEMS WITH INTERPRETATION

Aims-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 stain ing in a wide range of tumour types. Methods-A total of 283 neoplasms were examined for immunohistochemical expression of the c-erbB-2 oncop rotein. 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 t wo point scale. A minimum of two weeks elapsed between assessments usi ng the differing scales. Results-Positive membrane staining was docume nted by one or more observers in 16.6% of tumours examined. This posit ivity was largely restricted to bladder, renal, and breast tumours. Th e overall level of disagreement as to the presence or absence of membr anous staining was 11.3%. Cytoplasmic staining was identified in 55.5% of tumours studied. The level of disagreement as to the presence or a bsence of cytoplasmic staining was 26.5%. Conclusions-Intraobserver va riability was minimal, indicating that each pathologist was adhering t o internal reproducible standards. Interobserver variability was great er, indicating that the interpretation of c-erB-2 immunostaining may r equire set guidelines. It is suggested that assessment should be refer enced to a standard positive control, that a three tier system for gra ding of intensity and a two tier system for grading of extent should b e adopted, and that the evaluation should be agreed by at least two pa thologists. The presence of cytoplasmic staining should continue to be routinely recorded until its biological role and clinical implication s are fully understood.