Ki-67 Proliferation Index in Pancreatic Endocrine Tumors: Comparison with Mitotic Count, Interobserver Variability, and Impact on Grading.
Tanya A Rege, Emily E King, Justine A Barletta, Andrew M Bellizzi. Brigham and Women's Hospital, Boston, MA
Background: The biologic potential of pancreatic endocrine tumors (PETs) is notoriously difficult to predict. Several grading schemes exist, including those proposed by the World Health Organization (WHO) and European Neuroendocrine Tumor Society (ENETS). Mitotic count (MIT) and Ki-67 proliferation index (PI), among the best studied prognostic features, are essential components of these classifications. Despite this, many laboratories do not routinely perform Ki-67 immunohistochemistry (IHC), and if done, quantification methods vary. Ideal PI cutpoints are debated. Much remains to be learned about the relationship between MIT and PI, reproducibility of PI assessments, and impact of PI on grading.
Design: PETs were retrieved and the following recorded: age, sex, tumor size, metastases. One pathologist performed a mitotic count (MIT). Ki-67 IHC was performed on a representative block, and 3 study pathologists each quantified the PI by 2 separate methods: gestalt estimate and computer-assisted formal quantification (QUANT) based on counting ≥ 200 tumor cells. PI was assessed in areas of highest labeling. Correlation coefficients and kappa statistics were calculated; p<0.05 was considered significant.
Results: 55 PETs were evaluated (26M, 29F; mean age 58.1 [range 26-88]; mean size 4 cm [range 0.5-18 cm]; metastasis 16). MIT significantly correlated with gestalt PI and QUANT: r2 0.7677, 0.7774 (p<0.05). The gestalt PI and QUANT were nearly perfectly correlated: r2 0.9911. The gestalt under- and overestimated QUANT in 37 and 15 cases. Kappas for various 2 and 3-tiered Ki-67 cutpoints and a case-by-case comparison of MIT vs QUANT are presented below.
|≤2% vs >2%||0.7789||0.7329|
|≤5% vs >5%||0.7348||0.8073|
|≤2% vs >2-20% vs >20%||0.7404||0.6641|
|≤5% vs >5-20% vs >20%||0.6435||0.6990|
|Mitotic Figures per 10 HPF||G1 ≤2%||G2 >2-20%||G3 >20%|