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Multiplexed Fluorescent Immunohistochemical Staining, Imaging, and Analysis in Histological Samples of Lymphoma
Published on: January 9, 2019
Quantitative image analysis in the assessment of diffuse large B-cell lymphoma
Devon S Chabot-Richards1, David R Martin, Orrin B Myers
1Department of Pathology, University of New Mexico, Albuquerque, NM, USA.
Insights
Pathologist assessment of Ki-67 proliferation rates in diffuse large B-cell lymphoma showed a trend toward poorer survival, unlike quantitative image analysis. Pathologist estimates may be more clinically relevant despite good correlation with automated methods.
Area of Science:
- Oncology
- Pathology
- Biomedical Engineering
Background:
- Proliferation rates in diffuse large B-cell lymphoma (DLBCL) are linked to patient outcomes, but estimates vary.
- Traditionally, Ki-67 immunohistochemistry assessed by pathologists determines proliferation, yet its prognostic value is debated.
- Quantitative image analysis offers a potential alternative for precise proliferation assessment.
Purpose of the Study:
- To compare Ki-67 proliferation rate estimation between pathologists and a quantitative image analysis algorithm in DLBCL.
- To evaluate the association of both estimation methods with patient survival outcomes.
- To determine if quantitative image analysis provides superior prognostic information compared to pathologist assessment.
Main Methods:
- Eighty-four DLBCL cases were analyzed using WHO criteria.
- Ki-67 percentage positivity was recorded from original pathologist reports.
- The same slides underwent quantitative image analysis using a validated algorithm.
- Survival data was collected via chart review.
Main Results:
- Pathologist and quantitative image analysis Ki-67 estimates were significantly correlated (P<0.001).
- Pathologist Ki-67 percentages were significantly higher than quantitative analysis (P=0.021), with less agreement at lower percentages.
- Neither method showed a statistically significant association with survival, though a trend of worse survival with higher pathologist-estimated Ki-67 was observed.
Conclusions:
- Pathologist assessment of Ki-67 may hold greater prognostic significance for DLBCL survival than quantitative image analysis, despite good correlation between methods.
- Pathologists might excel at identifying prognostically relevant tumor areas.
- Further studies with larger cohorts are needed to confirm the statistical significance of these findings and the clinical utility of quantitative image analysis in DLBCL.
Abstract:
Proliferation rates in diffuse large B-cell lymphoma have been associated with conflicting outcomes in the literature, more often with high proliferation associated with poor prognosis. In most studies, the proliferation rate was estimated by a pathologist using an immunohistochemical stain for the monoclonal antibody Ki-67. We hypothesized that a quantitative image analysis algorithm would give a more accurate estimate of the proliferation rate, leading to better associations with survival. In all, 84 cases of diffuse large B-cell lymphoma were selected according to the World Health Organization criteria. Ki-67 percentage positivity estimated by the pathologist was recorded from the original report. The same slides were then scanned using an Aperio ImageScope, and Ki-67 percentage positivity was calculated using a computer-based quantitative immunohistochemistry nuclear algorithm. In addition, chart review was performed and survival time was recorded. The Ki-67 percentage estimated by the pathologist from the original report versus quantitative image analysis was significantly correlated (P<0.001), but pathologist Ki-67 percentages were significantly higher than quantitative image analysis (P=0.021). There was less agreement at lower Ki-67 percentages. Comparison of Ki-67 percentage positivity versus survival did not show significant association either with pathologist estimate or quantitative image analysis. However, although not significant, there was a trend of worse survival at higher proliferation rates detected by the pathologist but not by quantitative image analysis. Interestingly, our data suggest that the Ki-67 percentage positivity as assessed by the pathologist may be more closely associated with survival outcome than that identified by quantitative image analysis. This may indicate that pathologists are better at selecting appropriate areas of the slide. More cases are needed to assess whether this finding would be statistically significant. Due to the good correlation between pathologist estimate and quantitative image analysis, there is no substantial benefit to using quantitative image analysis at this point of time.
