Phospho-Histone H3 as a Tool for Improved Mitotic Counting and Risk Assessment in Gastrointestinal Stromal Tumors: A Study of 241 Cases

Background:Cell mitotic count is a core indicator for risk stratification (RS) in gastrointestinal stromal tumors (GIST).Studies have shown that phospho-histone H3 (PHH3) can specifically recognize mitotic figures, but the consistency of this method with the traditional hematoxylin-eosin (HE) method, the consistency among different observers, and the counting efficiency remain unclear.This study aimed to evaluate risk stratification in 241 patients with GIST using the cell proliferation marker PHH3 and cell mitosis counts. Material/Methods:We collected data from 241 patients with GIST who underwent radical surgical resection.Specimens were stained with HE and PHH3 immunohistochemistry. Three pathologists conducted the mitotic count on HE (MC-HE) and the mitotic count on PHH3 (MC-PHH3) in 5-mm 2 areas of tumor "hotspots" under blinded conditions.The counting results, consistency of RS, counting time, and inter-observer differences were compared, and the correlation with clinical and pathological parameters was analyzed. Results:There was a strong correlation between MC-PHH3 and MC-HE (r=0.879,P<0.01).The consistency rate of RS based on MC-PHH3 was 95%, with 8 cases upgraded and 4 cases downgraded.The average counting time of MC-PHH3 was significantly shorter than that of MC-HE (P<0.05).In terms of inter-observer consistency, the intra-class correlation coefficient of MC-PHH3 was 0.710, higher than the 0.648 of MC-HE.Both counting methods were significantly correlated with tumor size, whether it was ruptured, RS, and necrosis (P<0.05). Conclusions:PHH3 serves as a valuable adjunct to enhance the reliability and efficiency of pathological assessment in GIST.