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

Yang, Libo; Zhang, Zhang; Li, Jiayuan; Chen, Min; Yang, Jieliang; Fu, Jing; Bu, Hong; Tang, Shaoxian; Liu, Yueping; Li, Huixiang; Li, Xiaomei; Xu, Fangping; Teng, Xiaodong; Yang, Yinghong; Ma, Yun; Guo, Shuangping; Wang, Jinfen; Guo, Deyu

doi:10.7150/jca.25586

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J Cancer 2018; 9(13):2327-2333. doi:10.7150/jca.25586 This issue Cite

Research Paper

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 Li³, Min Chen¹, Jieliang Yang¹, Jing Fu⁴, Hong Bu^1,2*✉, Shaoxian Tang⁵, Yueping Liu⁶, Huixiang Li⁷, Xiaomei Li⁸, Fangping Xu⁹, Xiaodong Teng¹⁰, Yinghong Yang¹¹, Yun Ma¹², Shuangping Guo¹³, Jinfen Wang¹⁴, Deyu Guo¹⁵

1. Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
2. Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
3. Department of Epidemiology and Biostatistics, West China School of Public Health, Sichuan University, Chengdu, Sichuan Province, China.
4. Department of Pathology, Sichuan Academy of Medical Sciences & Sichuan Provincial People' s Hospital, Chengdu, Sichuan Province, China.
5. Department of Pathology, Shanghai Cancer Center, Fudan University, Shanghai, China.
6. Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
7. Department of Pathology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
8. Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, China.
9. Department of Pathology and Laboratory Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, China.
10. Department of Pathology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
11. Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China.
12. Department of Pathology, Affiliated Tumor Hospital, Guangxi Medical University, Nanning, Guangxi Province, China.
13. Department of Pathology, Xijing Hospital, the Air Force Military Medical University, Xi'an, Shanxi Province, China.
14. Department of Pathology, Shanxi Cancer Hospital, Taiyuan, Shanxi Province, China.
15. Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
^* Both Zhang Zhang and Hong Bu equally contributed to this article for correspondence

Citation:

Yang L, Zhang Z, Li J, Chen M, Yang J, Fu J, Bu H, Tang S, Liu Y, Li H, Li X, Xu F, Teng X, Yang Y, Ma Y, Guo S, Wang J, Guo D. 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. J Cancer 2018; 9(13):2327-2333. doi:10.7150/jca.25586. https://www.jcancer.org/v09p2327.htm

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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, HER2, Immunohistochemistry, Fluorescence in situ hybridization

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APA

Yang, L., Zhang, Z., Li, J., Chen, M., Yang, J., Fu, J., Bu, H., Tang, S., Liu, Y., Li, H., Li, X., Xu, F., Teng, X., Yang, Y., Ma, Y., Guo, S., Wang, J., Guo, D. (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. Journal of Cancer, 9(13), 2327-2333. https://doi.org/10.7150/jca.25586.

ACS

Yang, L.; Zhang, Z.; Li, J.; Chen, M.; Yang, J.; Fu, J.; Bu, H.; Tang, S.; Liu, Y.; Li, H.; Li, X.; Xu, F.; Teng, X.; Yang, Y.; Ma, Y.; Guo, S.; Wang, J.; Guo, D. 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. J. Cancer 2018, 9 (13), 2327-2333. DOI: 10.7150/jca.25586.

NLM

CSE

Yang L, Zhang Z, Li J, Chen M, Yang J, Fu J, Bu H, Tang S, Liu Y, Li H, Li X, Xu F, Teng X, Yang Y, Ma Y, Guo S, Wang J, Guo D. 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. J Cancer. 9(13):2327-2333.

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