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. 2015 May 1;8(5):4418-26.
eCollection 2015.

Value of counting positive PHH3 cells in the diagnosis of uterine smooth muscle tumors

Shu-Jie Pang  1 , Cheng-Cheng Li  2 , Yan Shen  1 , Yian-Zhu Liu  3 , Yi-Quan Shi  4 , Yi-Xin Liu  1
Affiliations

Value of counting positive PHH3 cells in the diagnosis of uterine smooth muscle tumors

Shu-Jie Pang et al. Int J Clin Exp Pathol. .

Abstract

The diagnosis of uterine smooth muscle tumors including leiomyosarcomas (LMS), smooth muscle tumors of uncertain malignant potential (STUMP), bizarre (atypical) leiomyoma (BLM), mitotically active leiomyoma (MAL) and leiomyoma (LM) depends on a combination of microscopic features, such as mitoses, cytologic atypia, and coagulative tumor cell necrosis. However, a small number of these tumors still pose difficult diagnostic challenges. The assessment of accurate mitotic figures (MF) is one of the major parameters in the proper classification of uterine smooth muscle tumors. This assessment can be hampered by the presence of increased number of apoptotic bodies or pyknotic nuclei, which frequently mimic mitoses. Phospho-histone H3 (PHH3) is a recently described immunomarker specific for cells undergoing mitoses. In our study, we collected 132 cases of uterine smooth muscle tumors, including 26 LMSs, 16 STUMPs, 30 BLMs, 30 MALs and 30 LMs. We used mitosis specific marker PHH3 to count mitotic indexes (MI) of uterine smooth muscle tumors and compared with the mitotic indexes of hematoxylin and eosin (H&E). There is a positive correlation with the number of mitotic figures in H&E-stained sections and PHH3-stained sections (r=0.944, P<0.05). The ratio of PHH3-MI to H&E-MI has no statistically significant difference in each group except for LMs (P>0.05). The counting value of PHH3 in LMSs have significantly higher than STUMPs, BLMs, MALs and LMs (P<0.001) and the counting value of PHH3 is 1.5±0.5 times of the number of mitotic indexes in H&E. To conclude, our results show that counting PHH3 is a useful index in the diagnosis of uterine smooth muscle tumors and it can provide a more accurate index instead of the time-honored mitotic figure counts at a certain ratio.

Keywords: PHH3; Uterine smooth muscle tumors; immunohistochemical; mitotic index.

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Figures

Figure 1
Figure 1
Histopathology of leiomyosarcoma (A), uncertain malignant potential (B). Expression of PHH3 in leiomyosarcoma (C), uncertain malignant potential (D). Phosphohistone-H3 PHH3 staining, mitotic figures stain chocolate brown, leiomyosarcoma has more mitotic figures than uncertain malignant potential (C, D). Inset: high-power detail of one anti-PHH3-immunostained mitotic figure in leiomyosarcoma and high-power detail of H&E in all 2 cases. (H&E×200; IHC×200).
Figure 2
Figure 2
Histopathology of mitotically active leiomyoma (A), bizarre (atypical) leiomyoma (B) and leiomyomas (C). Expression of PHH3 in mitotically active leiomyoma (D), bizarre (atypical) leiomyoma (E) and leiomyomas (F). Phosphohistone-H3 PHH3 staining, mitotic figures stain chocolate brown. Inset: high-power detail of H&E in all 3 cases. (H&E×200; IHC×200).
Figure 3
Figure 3
Results of MI quantitation on H&E-stained sections, anti-PHH3- labeled MI, proliferation index ki-67 and their relationships in 132 uterine smooth muscle tumors. The polynomial regressions are shown in green, blue and khaki.
Figure 4
Figure 4
A. PHH3-MI/H&E-MI (/10HPF) in all five groups of uterine smooth muscle tumors. Except LM, the means of the rate are almost equal in the rest four groups. B. Positive ki-67 cells/HE-MI (/10HPF) in all five groups of uterine smooth muscle tumors. The means of the rate are jagged in all five groups.
Figure 5
Figure 5
A. PHH3-MI per 10 HPF in all 5 groups of uterine smooth muscle tumors. B. H&E-MI per 10 HPF in all 5 groups of uterine smooth muscle tumors. C. Positive ki-67 cells per 10 HPF in all 5 groups of uterine smooth muscle tumors. Comparison of the three picture, We can find A and B is closer to scatter distribution, and the gap is big between A and C.
Figure 6
Figure 6
A. There are many pyknotic/degenerating hyperchromatic nuclei in this case. Medium magnification of LMS on hematoxylin and eosin section where mitotic figures were not readily identified. B. Mitotic indexes reveal a strong brown staining of condensed chromosome. (H&E×200; IHC×200).
Figure 7
Figure 7
Histopathology (A) and expression of PHH3 (B) in myxoid leiomyosarcoma (H&E×200; IHC×200) Inset: high-power detail of one anti-PHH3-immunostained mitotic figure.
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