pHH3: Useful Marker for Evaluating Mitotic Activity in Astrocytic and Meningeal Tumors
JH Seo, JK Myung, SH Park. Seoul National University Hospital, Seoul, Republic of Korea
Background: Mitotic count is the important criteria for grading and prognosis of most of CNS tumors. Immunohistochemical staining (IHC) for anti-phospho-histone H3 (pHH3), is previously reported that determines mitotic activity rapidly and separates mitotic figures from apoptotic nuclei easily and objectively. Therefore we compared the result of the mitotic count using anti-pHH3 IHC, conventional mitotic count on H&E slide and the Ki-67 labeling index and investigated any nonspecific staining of pHH3 in various grades of astrocytic and meningothelial tumors.
Design: Total 125 cases including 44 astrocytic tumors and 81 meningothelial tumors were investigated. For determining mitotic activity, the highest mitotic count per 10 HPF and the Ki-67 labeling index were determined. For pHH3, number of positive nuclei per 10 HPF was counted, and when the labeled nuclei were not clearly identified as mitotic figures, pHH3 labeling index was calculated with the same method for Ki-67.
Results: pHH3 was specifically positive in mitotic nuclei in astrocytic tumors but in meninigioma, nonspecific positive nuclei were found despite of extremely high dilution of pHH3 from 1:10,000 to 1:200,000. In 75.2% (81.8% of astrocytic tumors and 71.6% of meningothelial tumors) of studied tumors, the number of pHH3 positive mitoses is higher than conventional mitotic counting. In astrocytic tumors, pHH3-positive nuclei per 10HPF was well correlated with both Ki-67 labeling indices (correlation coefficient= 0.6 p<0.001) and WHO-grade of tumors (correlation coefficient=0.57 p=0.001). In meningiothelial tumors, the number of pHH3-postivie mitoses per 10HPF was well correlated with WHO-grade of tumors (correlation coefficient=0.76, p<0.001). However, pHH3 labeling indices, which include non-mitotic nuclei was well correlated with mitotic activity (correlation coefficient=0.55, p=0.02) and Ki-67 labeling indices (correlation coefficient=0.60, p=0.001), but not with WHO-grade of tumors.
Conclusions: pHH3 immunostaining was helpful for evaluating the mitotic activity of astrocytic tumors, but in meningiomas, it was not helpful because of nonspecific staining. Since pHH3 was more sensitive to detect mitoses than conventional counting on routine H&E slides, the criteria of mitoses for the grading of astrocytic and menigeal tumors should be shifted, otherwise we have to change the grade of the tumor after counting of mitoses on pHH3 immunostaining.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 240, Tuesday Afternoon