Lili Chen1, Yanyang Chen1, Zhongpeng Xie2, Jiao Luo3,1, Yuefeng Wang1, Jianwen Zhou3, Leilei Huang1, Hongxia Li1, Linhai Wang4, Pei Liu4, Man Shu1, Wenhui Zhang1, Zunfu Ke5,6,7. 1. Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. 2. Zhongshan School of Medicine, Sun Yat-sen University, No. 74, ZhongShan Second Road, Guangzhou, 510080, China. 3. Molecular Diagnosis and Gene Testing Center, The First Affiliated Hospital, Sun Yat-sen University, No. 58, ZhongShan Second Road, Guangzhou, 510080, China. 4. Beijing OriginPoly BioTec Co., Ltd, Beijing, China. 5. Molecular Diagnosis and Gene Testing Center, The First Affiliated Hospital, Sun Yat-sen University, No. 58, ZhongShan Second Road, Guangzhou, 510080, China. kezunfu@mail.sysu.edu.cn. 6. Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. kezunfu@mail.sysu.edu.cn. 7. Institute of Precision Medicine, Sun Yat-sen University, Guangzhou, China. kezunfu@mail.sysu.edu.cn.
Abstract
PURPOSE: Currently, the most commonly applied method for the determination of breast cancer subtypes is to test estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 by immunohistochemistry (IHC). However, the IHC method has substantial intraobserver and interobserver variability. ESR1, PGR, ERBB2, and MKi67 mRNA tests by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay may improve the diagnostic objectivity and efficiency. Here, we compared the concordance between RT-qPCR and IHC for assessment of the same biomarkers and evaluated the subtypes. METHODS: A total of 265 eligible cases were divided into a training cohort and a validation cohort, and the expressions of ER/ESR1, PR/PGR, HER2/ERBB2, and Ki67/MKI67 were tested by IHC and RT-qPCR. Then, the appropriate cutoff of RT-qPCR was calculated in the training cohort. The concordance between RT-qPCR and IHC was calculated for individual marker. In addition, we investigated the subtypes based on the RT-qPCR results. RESULTS: The Spearman correlation coefficients between ER/ESR1, PR/PGR, HER2/ERBB2, and Ki67/MKI67 by IHC and RT-qPCR were 0.768, 0.699, 0.762, and 0.387, respectively. The cutoff values for the RT-qPCR assay of ESR1 (1%), PGR (1%), ERBB2, and MKi67 (14%) were 35.539, 32.139, 36.398, and 29.176, respectively. The overall percent agreement (OPA) between ER/ESR1, PR/PGR, HER2/ERBB2, and Ki67/MKI67 by IHC and RT-qPCR was 92.48%, 73.68%, 92.80%, and 74.44%, respectively. A total of 224 (84.53%) specimens were concordant for the breast cancer subtypes (IHC-based type) by RT-qPCR. CONCLUSION: Evaluation of breast cancer biomarker status by RT-qPCR was highly concordant with IHC. RT-qPCR can be used as a supplementary method to detect molecular markers of breast cancer.
PURPOSE: Currently, the most commonly applied method for the determination of breast cancer subtypes is to test estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 by immunohistochemistry (IHC). However, the IHC method has substantial intraobserver and interobserver variability. ESR1, PGR, ERBB2, and MKi67 mRNA tests by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay may improve the diagnostic objectivity and efficiency. Here, we compared the concordance between RT-qPCR and IHC for assessment of the same biomarkers and evaluated the subtypes. METHODS: A total of 265 eligible cases were divided into a training cohort and a validation cohort, and the expressions of ER/ESR1, PR/PGR, HER2/ERBB2, and Ki67/MKI67 were tested by IHC and RT-qPCR. Then, the appropriate cutoff of RT-qPCR was calculated in the training cohort. The concordance between RT-qPCR and IHC was calculated for individual marker. In addition, we investigated the subtypes based on the RT-qPCR results. RESULTS: The Spearman correlation coefficients between ER/ESR1, PR/PGR, HER2/ERBB2, and Ki67/MKI67 by IHC and RT-qPCR were 0.768, 0.699, 0.762, and 0.387, respectively. The cutoff values for the RT-qPCR assay of ESR1 (1%), PGR (1%), ERBB2, and MKi67 (14%) were 35.539, 32.139, 36.398, and 29.176, respectively. The overall percent agreement (OPA) between ER/ESR1, PR/PGR, HER2/ERBB2, and Ki67/MKI67 by IHC and RT-qPCR was 92.48%, 73.68%, 92.80%, and 74.44%, respectively. A total of 224 (84.53%) specimens were concordant for the breast cancer subtypes (IHC-based type) by RT-qPCR. CONCLUSION: Evaluation of breast cancer biomarker status by RT-qPCR was highly concordant with IHC. RT-qPCR can be used as a supplementary method to detect molecular markers of breast cancer.
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