Cancer cell metabolism and colorectal cancer survival

Abstract

BackgroundScoring of immunohistochemistry (IHC) staining is often done by non-pathologists, especially in large-scale tissue microarray (TMA)-based studies.Studies on the validity and reproducibility of scoring results from non-pathologists are 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 localization (nucleus/membrane/cytoplasm). MethodsThree non-pathologists were trained in recognizing adenocarcinoma and IHC scoring by a senior histopathologist.Kappa statistics were used to analyze inter-observer and intraobserver agreement for 6,249 TMA cores from a colorectal cancer series. ResultsInter-observer agreement between non-pathologists (independently scored) and the histopathologist was "substantial" for nuclear and membranous IHC markers (ᴋ range = 0.67-0.75 and ᴋ range = 0.61-0.69,respectively), and "moderate" for the cytoplasmic IHC marker (ᴋ range = 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 (ᴋ nuclear = 0.74; ᴋ membranous = 0.73; ᴋ cytoplasmic = 0.57).Inter-observer agreement between non-pathologists was "substantial" (ᴋ nuclear = 0.78; ᴋ membranous = 0.72; ᴋ cytoplasmic = 0.61).Intra-observer agreement of non-pathologists was "substantial" to "almost perfect" (ᴋ nuclear,range = 0.83-0.87;ᴋ membranous,range = 0.75-0.82;ᴋ cytoplasmic = 0.69).Overall, agreement was lowest for the cytoplasmic IHC marker. ConclusionsThis study shows that adequately trained non-pathologists are able to generate reproducible IHC scoring results, that are similar to those of an experienced histopathologist.A combination score of at least two non-pathologists yielded optimal results. ImpactNon-pathologists can generate reproducible IHC results after appropriate training, making analyses of large-scale molecular pathological epidemiology studies feasible within an acceptable time frame.