Abstract 3420: Expression and significance of proliferation markers phosphohistone H3, Ki-67/MIB-1, and survivin in gastrointestinal stromal tumors
Authors: Ming Wang, Benedict Grissmann, Alexander Marx, Cleo-Aron Weiss, Maria Deligianni, Djeda Belharazem, Hui Cao, Peter Hohenberger
Journal: Cancer Research (2015)

Abstract Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Mitotic index (MI) is an essential risk factor for predicting recurrence of GIST. However, the inter-observer disagreement and the selection bias of the area for counting limit the reliability and reproducibility of risk-stratification based on traditional MI counting method. Phosphohistone H3 (PHH3), a novel mitosis-specific antibody, has been proven as a promising marker for facilitating MFs identification in several types of tumors. The purpose of present study is to explore the feasibility and reliability of PHH3-based mitosis counting methods in GISTs and to study the correlation between PHH3 and other two proliferation markers Ki67/MIB-1 and survivin. Methods: 83 GIST formalin-fixed paraffin-embedded (FFPE) specimens were enrolled in this study. The mitotic count was assessed either on hematoxylin and eosin sections (H&amp;E) or on PHH3 immuno-stained sections. The proliferation activity of tumors was also evaluated by immuno-staining of Ki67/MIB-1 and survivin. The interrelationship between these indices was analyzed statistically with Spearman rank coeffcients. Continuous variables not following the normal distribution were compared using Mann-Whitney U test between two groups or using Kruskal-Wallis H test among more than two groups. SPSS statistical software program, version 20.0 was used and all results were considered significant if p&amp;lt;0.05. Results: PHH3-based mitosis counting showed better inter-rate reliability (ICC 0.909 vs 0.821, p&amp;lt; 0.03) and stronger correlation with risk grade and clinical outcome than H&amp;E-based mitoses counting. Both the labeling indices (LI) of Ki67/MIB-1 and survivin (r = 0.737, p&amp;lt;0.0001) were strongly correlated to risk grade, clinical outcome, and PHH3-based mitoses count, which was also validated by immunofluorescence and immunocytochemical staining (r = 0.644, p&amp;lt;0.002). Conclusion: PHH3 could significantly facilitate determining the mitotic rate in GIST evaluation with superior inter-rate reliability. PHH3, Ki67/MIB-1, and survivin are co-expressed in GIST and their expressions are strongly correlated. Combined use of these markers is a promising technique for evaluating the prognosis of GIST and tailoring the treatment. Citation Format: Ming Wang, Benedict Grissmann, Alexander Marx, Cleo-Aron Weiss, Maria Deligianni, Djeda Belharazem, Hui Cao, Peter Hohenberger. Expression and significance of proliferation markers phosphohistone H3, Ki-67/MIB-1, and survivin in gastrointestinal stromal tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3420. doi:10.1158/1538-7445.AM2015-3420