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BioMed Research International
Volume 2018, Article ID 1013640, 10 pages
https://doi.org/10.1155/2018/1013640
Research Article

Identification of Phosphohistone H3 Cutoff Values Corresponding to Original WHO Grades but Distinguishable in Well-Differentiated Gastrointestinal Neuroendocrine Tumors

1Department of Surgery, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, 150 Seongan-ro, Gangdong-gu, Seoul 05355, Republic of Korea
2Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, 170beon-gil, 22 Gwanpyeong-ro, Dongan-gu, Anyang-si, Gyeonggi-do 14068, Republic of Korea
3Research Institute for Complementary & Alternative Medicine, Hallym University, 40 Seokwoo-Dong, Hwaseong, Gyeonggi-do 445-170, Republic of Korea
4Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, 170beon-gil, 22 Gwanpyeong-ro, Dongan-gu, Anyang-si, Gyeonggi-do 14068, Republic of Korea
5Department of Pathology, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Republic of Korea
6Department of Pathology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, 150 Seongan-ro, Gangdong-gu, Seoul 05355, Republic of Korea
7Department of Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, 170beon-gil, 22 Gwanpyeong-ro, Dongan-gu, Anyang-si, Gyeonggi-do 14068, Republic of Korea

Correspondence should be addressed to Mi Jung Kwon; rk.ro.myllah@99knalum

Received 16 November 2017; Accepted 26 February 2018; Published 27 March 2018

Academic Editor: Naoaki Sakata

Copyright © 2018 Min Jeong Kim et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Mitotic counts in the World Health Organization (WHO) grading system have narrow cutoff values. True mitotic figures, however, are not always distinguishable from apoptotic bodies and darkly stained nuclei, complicating the ability of the WHO grading system to diagnose well-differentiated neuroendocrine tumors (NETs). The mitosis-specific marker phosphohistone H3 (PHH3) can identify true mitoses and grade tumors reliably. The aim of this study was to investigate the correspondence of tumor grades, as determined by PHH3 mitotic index (MI) and mitotic counts according to WHO criteria, and to determine the clinically relevant cutoffs of PHH3 MI in rectal and nonrectal gastrointestinal NETs. Mitotic counts correlated with both the Ki-67 labeling index and PHH3 MI, but the correlation with PHH3 MI was slightly higher. The PHH3 MI cutoff ≥4 correlated most closely with original WHO grades for both rectal NETs. A PHH3 MI cutoff ≥4, which could distinguish between G1 and G2 tumors, was associated with disease-free survival in patients with rectal NETs, whereas that cutoff value showed marginal significance for overall survival in patient with rectal NETs. In conclusion, the use of PHH3 ≥4 correlated most closely with original WHO grades.