Validity And Reproducibility Of Immunohistochemical Scoring By Trained Non-Pathologists On Tissue Microarrays

Abstract Aims: Scoring of immunohistochemical (IHC) staining is often done by non-pathologists, especially in large-scale Tissue MicroArray (TMA)-based studies. Studies on the validity of scoring results from non-pathologists are very limited. Therefore, our main aim was to assess inter-observer agreement between trained non-pathologists and an experienced histopathologist for three IHC markers with different subcellular localisation (nucleus/membrane/cytoplasm). Methods and results: Three non-pathologists were trained in recognizing adenocarcinoma and IHC scoring by a senior histopathologist. Kappa statistics were used to analyse inter- and intra-observer agreement for 6249 TMA cores from a colorectal cancer (CRC) series. Inter-observer agreement between non-pathologists (independently scored) and the histopathologist was “substantial” for nuclear and membranous IHC markers (κrange=0.67-0.75 and κrange=0.61-0.69, respectively), and “moderate” for the cytoplasmic IHC marker (κrange=0.43-0.57). Scores of the three non-pathologists were also combined into a combination score (if at least two non-pathologists independently assigned the same score to a core, this was the combination score). This increased agreement with the pathologist (κnuclear=0.74; κmembranous=0.73; κcytopasmic=0.56). Inter-observer agreement between non-pathologists was “substantial” (κnuclear=0.78; κmembranous=0.72; κcytopasmic=0.61). Intra-observer agreement of non-pathologists was “substantial” to “almost perfect” (κnuclear,range=0.83-0.87; κmembranous,range=0.75-0.82; κcytopasmic,range=0.69-0.69). Overall, agreement was lowest for the cytoplasmic IHC marker. Conclusions: This study shows that adequately trained non-pathologists are able to produce similar IHC scoring results as an experienced histopathologist. Considering the histopathologist's score as the golden standard, we can conclude that trained non-pathologists can produce valid IHC results on TMA sections. A combination score of at least two non-pathologists yielded optimal results. Citation Format: Kelly Offermans, Josien C. Jenniskens, Iryna Samarska, Gregorio E. Fazzi, Colinda C. Simons, Kim M. Smits, Leo J. Schouten, Matty P. Weijenberg, Piet A. van den Brandt, Heike I. Grabsch. Validity and reproducibility of immunohistochemical scoring by trained non-pathologists on Tissue MicroArrays [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 830.