Qi Sun1,2, Qi Li1, Fuping Gao3, Hongyan Wu1, Yao Fu1, Jun Yang1, Xiangshan Fan4, Xiaobin Cui5, Xiaohong Pu6. 1. Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhong-Shan Road, Nanjing, 210008, Jiangsu, China. 2. Center for Digestive Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, Jiangsu, China. 3. Department of Pathology, Gaochun People's Hospital, Nanjing, 210008, Jiangsu, China. 4. Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhong-Shan Road, Nanjing, 210008, Jiangsu, China. fxs23@126.com. 5. Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhong-Shan Road, Nanjing, 210008, Jiangsu, China. cuixiaobin4363@foxmail.com. 6. Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhong-Shan Road, Nanjing, 210008, Jiangsu, China. xiaohongpu06@163.com.
Abstract
OBJECTIVE: Although HER2 has gradually become an important therapeutic target for colorectal cancer (CRC), a unified and standard HER2 scoring system was still not established in CRC, and the debatable results of immunohistochemistry and fluorescence in situ hybridization (FISH) in CRC requires further exploration. METHODS: In this study, we use five immunohistochemical (IHC) scoring criteria (i.e., IRS-p, IRS-m, GEA-s, GEA-b and HERACLES) and two FISH criteria to evaluate HER2 status, and further evaluate the correlation between HER2 status and clinicopathological features, survival in a large, unselected Chinese cohort of 664 CRCs. RESULTS: Finally, we set HER2/CEP17 ratio ≥ 2.0, or an average HER2 copy number ≥ 6.0 as FISH-positive threshold and the amplification rate of HER2 gene was 7.08% (47/664).The HER2 positivity (IHC 3+) was 2.71%, 3.16%, 2.56%, 2.71% and 3.16%, according to the IHC scoring criteria of IRS-p, IRS-m, GEA-s, GEA-b and HERACLES, respectively. Set FISH results as the golden standard; receiver-operating characteristic analysis showed that IRS-p had both high sensitivity and specificity than other IHC scoring systems to evaluate HER2 status. Based on IRS-p criterion, There were significant differences in tumor differentiation (p = 0.038), lymphatic vascular invasion (p = 0.001), pN stage (p value = 0.043), and overall survival (p < 0.001) among IHC score 0-3 + groups. Meanwhile, there were significant differences in pT stage (p = 0.031), pN stage (p = 0.009) and overall survival (p < 0.001) among FISH subgroups. CONCLUSION: The IRS-p criterion was more suitable for assessing the HER2 status in CRC patients than other IHC criteria. Whereas for FISH scoring system, only HER2/CEP17 < 2.0, meanwhile HER2cn < 4.0 and HER2cn ≥ 6.0 were subgroups with unique clinicopathological characteristics.
OBJECTIVE: Although HER2 has gradually become an important therapeutic target for colorectal cancer (CRC), a unified and standard HER2 scoring system was still not established in CRC, and the debatable results of immunohistochemistry and fluorescence in situ hybridization (FISH) in CRC requires further exploration. METHODS: In this study, we use five immunohistochemical (IHC) scoring criteria (i.e., IRS-p, IRS-m, GEA-s, GEA-b and HERACLES) and two FISH criteria to evaluate HER2 status, and further evaluate the correlation between HER2 status and clinicopathological features, survival in a large, unselected Chinese cohort of 664 CRCs. RESULTS: Finally, we set HER2/CEP17 ratio ≥ 2.0, or an average HER2 copy number ≥ 6.0 as FISH-positive threshold and the amplification rate of HER2 gene was 7.08% (47/664).The HER2 positivity (IHC 3+) was 2.71%, 3.16%, 2.56%, 2.71% and 3.16%, according to the IHC scoring criteria of IRS-p, IRS-m, GEA-s, GEA-b and HERACLES, respectively. Set FISH results as the golden standard; receiver-operating characteristic analysis showed that IRS-p had both high sensitivity and specificity than other IHC scoring systems to evaluate HER2 status. Based on IRS-p criterion, There were significant differences in tumor differentiation (p = 0.038), lymphatic vascular invasion (p = 0.001), pN stage (p value = 0.043), and overall survival (p < 0.001) among IHC score 0-3 + groups. Meanwhile, there were significant differences in pT stage (p = 0.031), pN stage (p = 0.009) and overall survival (p < 0.001) among FISH subgroups. CONCLUSION: The IRS-p criterion was more suitable for assessing the HER2 status in CRC patients than other IHC criteria. Whereas for FISH scoring system, only HER2/CEP17 < 2.0, meanwhile HER2cn < 4.0 and HER2cn ≥ 6.0 were subgroups with unique clinicopathological characteristics.
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