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Comparative Study
. 2016 Mar;69(3):255-9.
doi: 10.1136/jclinpath-2015-203174. Epub 2015 Sep 29.

The importance of tissue handling of surgically removed breast cancer for an accurate assessment of the Ki-67 index

Nobuyuki Arima  1 , Reiki Nishimura  2 , Tomofumi Osako  2 , Yasuyuki Nishiyama  2 , Mamiko Fujisue  2 , Yasuhiro Okumura  3 , Masahiro Nakano  3 , Rumiko Tashima  4 , Yasuo Toyozumi  5
Affiliations
Comparative Study

The importance of tissue handling of surgically removed breast cancer for an accurate assessment of the Ki-67 index

Nobuyuki Arima et al. J Clin Pathol. 2016 Mar.

Abstract

Aim: Insufficient attention for the Ki-67 immunohistochemistry has been given to the importance of tissue handling for surgical breast cancer specimens. We sought to investigate the effect of fixation status on the Ki-67.

Methods: We examined the effect of fixative, time to and duration of fixation using surgical specimens, and finally, compared the paired Ki-67 index in the tumour between core needle and surgical specimen.

Results: The Ki-67 was significantly higher when 10% neutral buffered formalin was used (p=0.0276). Insufficient fixation caused a drastic reduction in the Ki-67 index (p=0.0177), but not significant in oestrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). Sixteen hours delayed time to fixation also caused a reduction of the Ki-67 (p=0.0284), but not significant in ER. Prolonged fixation significantly led to a gradual reduction in the Ki-67 in a time-dependent manner, but not in both ER and HER2. Finally, cutting the tumour before fixation improved fixation status and consequently caused an increased level of the Ki-67 index (p=0.0181), which resulted in a strong correlation of the Ki-67 between core needle and surgical specimen (r=0.8595).

Conclusions: Tissue handling of surgical specimen is critical for assessing the Ki-67 compared with ER and HER2. We should pay more attention to tissue fixation status for the standard assessment of the Ki-67 index.

Keywords: BREAST CANCER; IMMUNOHISTOCHEMISTRY; PROLIFERATION; TUMOUR BIOLOGY.

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Figures

Figure 1
Figure 1
Effect of insufficient fixation on Ki-67 immunohistochemistry (IHC) in human epidermal growth factor receptor 2 (HER2)-positive cancer. Insufficient fixation caused a drastic reduction in the Ki-67 index from 33% to 5% in a HER2-positive cancer (A and B), while there was no significant change in the HER2 expression (C and D). (A and B) Ki-67 IHC; (C and D) HER2 IHC; (A and C) fixed for 48 h; (B and D) fixed for 3 h.
Figure 2
Figure 2
Effect of prolonged fixation on Ki-67 immunohistochemistry in oestrogen receptor (ER)-positive (A) and human epidermal growth factor receptor 2 (HER2)-positive (B) cancer. Prolonged fixation caused a gradual reduction in the Ki-67 index in a time-dependent manner (A and B, top), while there was no significant reduction in both ER (A, bottom) and HER2 (B, bottom) expression.
Figure 3
Figure 3
Comparison of the Ki-67 index between core needle and surgical specimen in the same tumour. The Ki-67 index in each of the 136 pairs of core needle and surgical specimen originating from the same tumour were analysed. The Ki-67 index independently scored were strongly correlated (Pearson's correlation coefficient=0.8595).
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