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. 2018 Jun 6;9(13):2327-2333.
doi: 10.7150/jca.25586. eCollection 2018.

A decision tree-based prediction model for fluorescence in situ hybridization HER2 gene status in HER2 immunohistochemistry-2+ breast cancers: a 2538-case multicenter study on consecutive surgical specimens

Libo Yang  1   2 , Zhang Zhang  1 , Jiayuan Li  3 , Min Chen  1 , Jieliang Yang  1 , Jing Fu  4 , Hong Bu  1   2 , Shaoxian Tang  5 , Yueping Liu  6 , Huixiang Li  7 , Xiaomei Li  8 , Fangping Xu  9 , Xiaodong Teng  10 , Yinghong Yang  11 , Yun Ma  12 , Shuangping Guo  13 , Jinfen Wang  14 , Deyu Guo  15
Affiliations

A decision tree-based prediction model for fluorescence in situ hybridization HER2 gene status in HER2 immunohistochemistry-2+ breast cancers: a 2538-case multicenter study on consecutive surgical specimens

Libo Yang et al. J Cancer. .

Abstract

Objective: To investigate the proportion of HER2 gene amplifications and the association between the HER2-IHC-staining pattern and gene status in IHC-2+ breast cancers according to 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. Methods: We retrospectively analyzed and re-evaluated the IHC-staining pattern of 2538 IHC-2+ surgical specimens of breast cancer from November 2014 to October 2015 in 12 institutions. All cases used for building a prediction model of HER2 gene amplification according to the IHC-staining pattern and were randomly divided into a training set (n = 1914) or validation set (n = 624). Results: The overall HER2 fluorescence in situ hybridization (FISH) amplification, non-amplification and equivocation rates in HER2 IHC-2+ cases were 17.8%, 76.2% and 6.0%, respectively. In the training set, cases that had ≤ 10% of cells with intense, complete and circumferential membrane staining or had > 85% of cells with complete membrane staining of any staining intensity tended to be HER2 gene amplified (77.0% and 60.5%, respectively). And cases with weak and incomplete membrane staining had the lowest amplification rate of 6.1%. The prediction model was constructed based on IHC-staining pattern in the training set and validated using a validation set. The positive and negative prediction values were 51.6% and 79.2%, respectively, in the validation set. Moreover, the HER2 copy number per cell was much higher in cases with amplification-associated staining patterns (7.84 and 8.75) than in cases with non-amplification-associated staining patterns (2.97 to 4.41, P < 0.05). Conclusions: In HER2 IHC-2+ breast cancers, the staining pattern is associated with the HER2 gene status. This finding is compatible with recommendations of 2013 ASCO/CAP guidelines.

Keywords: Breast Cancer; Fluorescence in situ hybridization; HER2; Immunohistochemistry.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Flow chart of this study. (FISH, fluorescence in situ hybridization; PPV, positive prediction value; NPV, negative prediction value).
Figure 2
Figure 2
Example of different intensity and integrity in immunohistochemistry (IHC) staining pattern. a. Weak and incomplete membrane staining; b. weak and complete membrane staining; c. moderate and incomplete membrane staining; d. moderate and complete membrane staining; e. intense, complete and circumferential membrane staining. (a-e, original magnification: ×400).
Figure 3
Figure 3
Decision-tree based prediction model of HER2 gene status and details on the number and ratio of different fluorescence in situ hybridization (FISH) results.
Figure 4
Figure 4
HER2 gene copy number per cell in different staining patterns
See this image and copyright information in PMC

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