ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2017
Synaptophysin-Ki67 double stain: a novel technique that improves interobserver agreement in the grading of well-differentiated gastrointestinal neuroendocrine tumors.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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9 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Ki-67 assessment of pancreatic neuroendocrine neoplasms: Systematic review and meta-analysis of manual vs. digital pathology scoring.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022Pooled it
- Defining hotspot for estimation of Ki-67 proliferation index of neuroendocrine tumors: QuPath algorithm vs. manual assessment.Journal of pathology informatics · 2026Article
- Hyams Grade and Ki-67 as Predictive Factors for Primary Treatment Failure in Olfactory Neuroblastoma.The Laryngoscope · 2025Article
- Automated AI-based grading of neuroendocrine tumors using Ki-67 proliferation index: comparative evaluation and performance analysis.Medical & biological engineering & computing · 2024Article
- Automated assessment of Ki-67 proliferation index in neuroendocrine tumors by deep learning.APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2022Article
- Article
- Automated quantification of Ki-67 index associates with pathologic grade of pulmonary neuroendocrine tumors.Chinese medical journal · 2019Article
- Comparison of Monitor-Image and Printout-Image Methods in Ki-67 Scoring of Gastroenteropancreatic Neuroendocrine Tumors.Endocrine pathology · 2019Article
- Immunohistochemical Biomarkers of Gastrointestinal, Pancreatic, Pulmonary, and Thymic Neuroendocrine Neoplasms.Endocrine pathology · 2018Review
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6 authors at 1 institution in 1 country.
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Abstract
A common problem in the assessment of Ki67 proliferative index in well-differentiated gastrointestinal neuroendocrine tumors is distinguishing tumor from non-tumor. This is because background stromal lymphocytes, entrapped non-neoplastic glands, and the delicate vascular network characteristic of neuroendocrine tumors frequently contain a subset of proliferating cells. Furthermore, in small biopsies, crush and cautery artifact can alter the morphologic appearance of tumor cells, making the Ki67 proliferative index more difficult to assess. To address these issues, we developed a synaptophysin-Ki67 double stain using a commercially available immunohistochemistry kit, allowing simultaneous visualization of tumor and proliferating nuclei. To test this method, three gastrointestinal pathologists individually graded 50 gastrointestinal neuroendocrine tumors first using synaptophysin-Ki67 double-stained slides and then, after a washout period, using Ki67-only stained slides (along with routine hematoxylin- and eosin-stained slides). Interobserver agreement on Ki67 proliferative index was moderate using the Ki67-only stained slides (intraclass correlation 0.51, 95% confidence interval: 0.35-0.66) and improved using the synaptophysin-Ki67 double stain (intraclass correlation 0.79, 95% confidence interval: 0.69-0.86). Similarly, interobserver agreement on tumor grade was fair with Ki67-only stained slides (κ=0.39, P<0.001) and improved with the double stain (κ=0.58, P<0.001). Analysis of individual pathologists' scores revealed that fewer total number of tumor cells counted correlated with higher grade designation and appeared to contribute to grade discordance. In tumors cited as particularly challenging to assess by the pathologists, three of four tumors were grade discordant with the Ki67-only stain, whereas all four tumors were grade concordant with the synaptophysin-Ki67 stain. The synaptophysin-Ki67 double stain is the first technique to address specifically the histomorphologic challenges of evaluating Ki67 proliferative index in well-differentiated gastrointestinal neuroendocrine tumors. Although further validation is needed, this study provides evidence that the synaptophysin-Ki67 double stain can improve interobserver agreement.
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