Interpretation of immunohistochemistry results of HER2/neu expression in invasive breast cancer: Evaluation of interobserver and intraobserver agreement in Iran

Abstract

11557 Background: The accurate determination of HER2 in invasive breast cancer has become a critical issue, particularly in context of the results of trastuzumab adjuvant therapy. The aim of this study is evaluation of inter- and intraobserver reproducibility in interpretation of HER2/neu immunostaining in invasive breast cancer in the context of lack of Fish facility, in Iran as a third world country. Methods: A total of 112 HER2/neu immunostains were independently evaluated by 4 pathologists using the criteria recommended by DAKO (0 to 3+ reflecting the intensity and pattern of the immunohistochemical signal present in 10% or more of tumor cells). After a session for receiving a consensus, the samples have been evaluated for the second time. Results: Complete agreement was achieved in 33 (29.5%) and 40 (35.7%) of 112 cases in the first and second examinations, respectively. Generally, interobserver agreement was moderate (kappa=0.42 in the first examination and 0.49 in the second one), with intermediate categories (1+, 2+) showing fair agreement and extreme categories (0, 3+) showing moderate agreement. Intraobserver agreement was also moderate (from the minimum kappa=0.53 to the maximum of 0.60). Considering three groups as negative (0/1+), weakly positive (2+) and strongly positive (3 +) interobserver agreement improved but still staying in the moderate level (kappa=0.54 and 0.60 in the first and second time, respectively) with score 2+ group showing the least level of agreement. However, with dividing the cases into two groups as, interobserver agreement improved to substantial level positive (2/3+), negative (0/1+) and kappa=0.68 and 0.75 in the first and second time, respectively). Also with this consideration, intraobserver agreement improved to substantial level (0.7 to 0.8). Conclusions: The standardization of IHC-HER2 protocols, tight adherence to guidelines and continuous educational programs using slide conference sessions, particularly associated with calibration against FISH, and periodic external controls are necessary for improvement of interobserver reproducibility in the third world. No significant financial relationships to disclose.