Evaluation of intra‐ and interobserver agreement and its clinical significance for scoring bcl‐2 immunohistochemical expression in diffuse large B‐cell lymphoma

Abstract

Immunohistochemistry (IHC) has become an essential part of diagnosis and clinical research in lymphomas. There is considerable heterogeneity, however, in IHC findings regarding expression rate and positivity cut-offs, which creates a degree of uncertainty that has prevented its incorporation for prognostic purposes. The purpose of the present study was to assess intra- and interobserver agreement in scoring bcl-2 expression on IHC. The study materials were 81 diffuse large B-cell lymphomas. Slides were processed in the same laboratory, and were analyzed independently and in a blinded manner by four pathologists twice, at least 1 month apart. The positivity rates ranged from 31% to 41% in the first evaluation, and from 30% to 43% in the second evaluation. The two analyses by the same pathologist gave concordant results in 88-93% of cases (kappa = 0.71-0.83). Complete agreement among all observers varied from 72% to 79%. The experience of the observer did not influence intra-observer concordance. Cooperative analysis of discordant slides led to consensus in all cases. The variation observed in scoring bcl-2 expression is acceptable for use in lymphoma diagnosis and classification. The use of IHC stratification, however, for clinical decisions regarding treatment will require standardization and centralized consensus review, and must await the results of ongoing prospective trials.

Quantitative comparison of immunohistochemical staining measured by digital image analysis versus pathologist visual scoring

“…Consequently, regions of negative and high-positive intensities may be overcalled leading to artificially-produced bimodal score distributions [23]. While pathologist-derived data have good to excellent intra- and inter-observer reproducibility [18-20], estimation of percentages of areas stained has only poor to good reproducibility [19]. Digital methods may provide more reliable data.…”

Quantitative comparison and reproducibility of pathologist scoring and digital image analysis of estrogen receptor β2 immunohistochemistry in prostate cancer

“…The long-term aims of our studies are to examine the association of PCa biomarkers with outcomes at the patient level. Traditionally, we and others in our field have used pathologist visual scoring, which has been shown to have good to excellent intra- and inter-pathologist reproducibility [ 4 , 6 , 35 ]. However, approximations of positive-staining area has only poor to good pathologist reproducibility [ 6 ], highlighting the need for improved methods.…”

Investigating Various Thresholds as Immunohistochemistry Cutoffs for Observer Agreement

“…One potential strategy to address the former is the use of a receiver operating characteristics (ROC) curve that can 7 help to identify an appropriate cut-off 1,5 . The latter issue can be answered by assessing the level of agreement between pathologists [6][7][8] .…”

“…A cut-off should be both clinically relevant and easily interpretable by pathologists. There is a tendency to focus more on the clinical relevance of the cut-off for a biomarker with less focus on the level of agreement between pathologists when they use it for scoring purposes 6,22 . Inter-and intra-observer variation of a cut-off is infrequently 8 analysed despite the fact that it is recognised as a potential barrier to clinical translation.…”