Application of Mitosis-Specific Antibody Phospho-Histone H3 in Neuroendocrine Tumors
Daisuke Nonaka. Christie Hospital and the University of Manchester, Manchester, United Kingdom
Background: Mitotic count provides an important parameter for grading and prognostication in a variety of tumors, including neuroendocrine tumors. For instance, in WHO classification, mitotic count, along with necrosis or Ki67, defines grading in neuroendocrine tumors of lung and GI tract. However, mitotic figure can be difficult to detect due to crush artifact, inappropriate fixation, presence of apoptosis and cellular degeneration, as is often the case in neuroendocrine tumors. Phospho-histone H3 (PHH3) has been reported as a useful marker to assist mitotic figure counting, and this study has investigated the utility of this marker in neuroendocrine tumors.
Design: Anti-PHH3 antibody (clone Ser28) was applied to a total of 60 resected and biopsied tumors from lung, appendix, small intestine, rectum, pancreas, thyroid and parathyroid, including carcinoid/NET, medullary carcinoma, parathyroid adenoma/carcinoma, and large cell neuroendocrine carcinoma. Anti-PHH3 and H&E were stained on consecutive sections, and mitotic figures on H&E and PHH3 stained sections were counted in 10 high power fields (x400) in the same area.
Results: Mitotic count on H&E and PHH3-staining, each designated as MC and PC, ranged from 0 to 21 and from 0 to 34, with average MC and PC of 1.725 and 4.925, respectively. Discrepancy between the two was mainly attributed to sensitivity of PHH3 staining, and poor fixation (usually in large tumor resection), degenerative change, and crush artifacts (particularly in biopsy) of the tumor.
Conclusions: PHH3 is a sensitive marker to detect mitotic figures in both resection and biopsy, with above-mentioned pitfalls, therefore mitotic count based on PHH3 staining would provide more accurate tumor grading.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 68, Wednesday Afternoon