J Pathol Transl Med.  2015 Jan;49(1):23-29. 10.4132/jptm.2014.10.08.

PHH3 as an Ancillary Mitotic Marker in Gastrointestinal Stromal Tumors

• Shin Y
• Hyeon J
• Lee B
• Ha SY
• Hong ME
• Do IG
• Kim KM

• KMID: 2381349
• DOI: http://doi.org/10.4132/jptm.2014.10.08

Abstract

BACKGROUND
Counting mitoses is subjective and time-consuming. The adjunctive diagnostic utility of a recently reported mitotic marker, phosphohistone H3 (PHH3), was investigated in gastrointestinal stromal tumors (GISTs).
METHODS
We reviewed 77 GISTs for several proliferative indices. These included the mitotic count per 50 high power fields (HPFs), the immunohistochemical Ki-67 labeling index and the immunohistochemical PHH3 mitotic index (MI). For comparison, Spearman's rank correlation and interclass correlation coefficient were used.
RESULTS
Mitotic counts ranged from 0-138 (mean, 7.57+/-2.34) and the PHH3 MI ranged from 0-126 per 50 HPFs (mean, 9.61+/-2.27). We found a positive correlation between mitotic counts and PHH3 MI (r=0.810, p<.001). The inter-observer correlation coefficient for three participants was 0.975 for mitotic counts and 0.940 for the PHH3 MI. When using the PHH3 MI instead of mitotic counts in the Armed Forces Institute of Pathology (AFIP) stratification criteria, 10 cases were reclassified. In one patient with a mitotic count of 2 and a PHH3 MI of 6 per 50 HPFs, distant metastasis occurred.
CONCLUSIONS
In GISTs, the PHH3 MI correlated adequately with mitotic counts and can be used as a useful adjunctive to count mitotic figures efficiently.

Keyword

Gastrointestinal stromal tumors; Mitosis; Ki-67; Biological marker

MeSH Terms

Arm
Biomarkers
Gastrointestinal Stromal Tumors*
Humans
Mitosis
Mitotic Index
Neoplasm Metastasis
Pathology

Figure

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  Fig. 1. A comparison of hematoxylin and eosin (A, C) and phophohistone H3 (PHH3) immunohistochemistry (B, D) in mitotic detection (arrows). Mitotic figures (arrows) are easily and quickly recognized with PHH3 immunohistochemistry.

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  Fig. 2. Hematoxylin and eosin (H&E) (A) and phophohistone H (PHH3) immunohistochemistry (B) in a case with delayed fixation. H&E shows no mitotic figures whereas PHH3 shows three mitotic figures in the same field (arrows).

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  Fig. 3. Mitosis and PHH3 positive cells in a patient with distant metastasis. Hematoxylin and eosin (H&E) staining shows a single mitotic figure. (B) H&E at higher magnification. (C) Phophohistone H3 (PHH3) immunohistochemistry highlights two mitotic figures in the same field (arrows). (D, E) PHH3 at higher magnification.

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