Department of Pathology and Resident Training Base, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Center for Cancer Precision Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Diagn Pathol. 2020 Mar 24;15(1):27. doi: 10.1186/s13000-020-00950-y.
Despite great progress in surgery and other treatments, the prognosis of patients with esophageal squamous cell carcinoma (ESCC) is still very poor. HER2 has strong therapeutic implications in certain cancers, such as breast cancer and gastric cancer. However, literature on the frequency of HER2 expression in ESCC is scarce. In the present study, HER2 protein expression, HER2 gene amplification and the relationship between HER2 status and clinicopathological characteristics were evaluated in a large cohort of Chinese ESCC patients.
A total of 857 consecutive ESCC patients who received radical esophagectomy without neoadjuvant therapy between January 2014 and October 2015 were included in this retrospective study. HER2 protein expression was analyzed by immunohistochemistry (IHC), and its correlation with clinicopathological parameters was assessed. In addition, 65 cases, including 13 HER2 overexpression (3+) cases and 52 HER2 equivocal (2+) cases from the 857-case cohort, and another 104 ESCC cases, including 1 HER2 overexpression (3+) case, 3 HER2 equivocal (2+) cases and 100 HER2 negative (1+/0) cases, were selected to construct tissue microarrays (TMAs). Dual-color in situ hybridization (DISH) was performed on the TMAs to assess HER2 gene amplification and the relationship with clinicopathological parameters.
We found HER2 overexpression (3+) status in 1.5% (13/857) of cases and HER2 equivocal (2+) status in 6.1% (52/857) of cases. HER2 IHC expression was significantly associated with gender (P = 0.028). However, there were no significant correlations between HER2 IHC expression and age, tumor differentiation, pT stage, pN stage, pM stage and pTNM stage (P > 0.05). Regarding the 169 cases analyzed by DISH, 14 (of 14, 100%) HER2 overexpression (3+) cases, 10 (of 55, 18.2%) HER2 equivocal (2+) cases, and 0 (of 100, 0%) HER2 negative (1+/0) cases showed HER2 gene amplification. HER2 gene amplification was not significantly associated with clinicopathological characteristics such as age, gender, tumor differentiation, pT stage, pN stage, pM stage and pTNM stage (P > 0.05).
Approximately 1.5% of the Chinese ESCC patients had HER2 overexpression based on IHC. IHC and DISH had a high concordance rate. These results provide valuable insight for the future treatment of ESCC.
尽管在手术和其他治疗方面取得了巨大进展，但食管鳞状细胞癌（ESCC）患者的预后仍然非常差。HER2 在某些癌症（如乳腺癌和胃癌）中具有很强的治疗意义。然而，关于 ESCC 中 HER2 表达频率的文献很少。在本研究中，我们评估了 857 例接受根治性食管切除术（无新辅助治疗）的中国 ESCC 患者的大量队列中 HER2 蛋白表达、HER2 基因扩增以及 HER2 状态与临床病理特征之间的关系。
本回顾性研究纳入了 2014 年 1 月至 2015 年 10 月期间接受根治性食管切除术（无新辅助治疗）的 857 例连续 ESCC 患者。通过免疫组织化学（IHC）分析 HER2 蛋白表达，并评估其与临床病理参数的相关性。此外，从 857 例队列中选择了 13 例 HER2 过表达（3+）病例和 52 例 HER2 不确定（2+）病例，以及另 104 例 ESCC 病例，包括 1 例 HER2 过表达（3+）病例、3 例 HER2 不确定（2+）病例和 100 例 HER2 阴性（1+/0）病例，构建组织微阵列（TMA）。对 TMA 进行双色原位杂交（DISH）以评估 HER2 基因扩增及其与临床病理参数的关系。
我们发现 1.5%（13/857）的病例存在 HER2 过表达（3+）状态，6.1%（52/857）的病例存在 HER2 不确定（2+）状态。HER2 IHC 表达与性别显著相关（P=0.028）。然而，HER2 IHC 表达与年龄、肿瘤分化、pT 分期、pN 分期、pM 分期和 pTNM 分期之间无显著相关性（P＞0.05）。对于通过 DISH 分析的 169 例病例，14 例（100%）HER2 过表达（3+）病例、10 例（55%）HER2 不确定（2+）病例和 0 例（100%）HER2 阴性（1+/0）病例均显示 HER2 基因扩增。HER2 基因扩增与年龄、性别、肿瘤分化、pT 分期、pN 分期、pM 分期和 pTNM 分期等临床病理特征无显著相关性（P＞0.05）。
约 1.5%的中国 ESCC 患者基于 IHC 存在 HER2 过表达。IHC 和 DISH 具有很高的一致性。这些结果为 ESCC 的未来治疗提供了有价值的见解。
