Immunostaining of phospho-histone H3 and Ki-67 improves reproducibility of recurrence risk assessment of gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) are the most common non-epithelial tumors in the digestive tract. Beyond surgery, therapeutic management depends on risk of recurrence. Risk evaluation of GIST takes into account location and size of the tumor, whether or not the tumor was intact or ruptured and mitotic index. The mitotic index lacks in intra- and interobserver reproducibility. In this study, we evaluated on 61 GISTs, the reproducibility of mitotic counting using classical hematoxylin-eosin-saffron (HES) staining, and its correlation with the mitotic count obtained through immunohistochemical staining for phospho-histone H3 (PHH3) and the proliferation index based upon Ki-67 immunostaining. Mitotic counts by HES and PHH3 staining and Ki-67 proliferation index were evaluated twice by three independent observers taking into account interpretation times per tumor for each technique. HES-based and PHH3-based mitotic counts and Ki-67 proliferation index correlated well and presented good intra- and interobserver reproducibility. PHH3 staining resulted in a slight but statistically significant difference of about two more mitotic figures per 5 mm² than the HES-based count, which might have put some borderline tumors in a different risk category. Immunohistochemical staining for PHH3 and Ki-67 allowed more rapid interpretation than mitotic counts based upon HES staining, but only PHH3 staining allows counting of mitoses. Immunostaining using anti-PHH3 and anti-Ki-67 antibodies will eventually provide improved recurrence risk stratification of GIST and may become effective ancillary tools in deciding on optimal therapeutic management.