Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus
Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus
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DOI：
10.1038/modpathol.3800712
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发表时间：
2007-01-01
期刊：
影响因子：
7.5
通讯作者：
Sauter, Guido
中科院分区：
文献类型：
--
作者：
Reichelt, Uta;Duesedau, Peer;Sauter, Guido
HER-2是基于抗体的乳腺癌治疗（赫赛汀）的靶标。为了评估这种治疗在食管癌中的潜在作用，研究了HER-2在原发性和转移性食管癌中的扩增和过表达。研究人员对255例原发性食管癌（110例腺癌和145例鳞状细胞癌）、89例淋巴结癌和33例远处转移癌构建了组织芯片。通过免疫组织化学（HercepTest (TM)）对载玻片进行分析；DAKO)和荧光原位杂交（FISH; PathVysiont; Vysis- Abbott）进行HER-2扩增和过表达。在16/110（15%）的腺癌和7/145（5%）的鳞状细胞癌中可见扩增。HER-2扩增与过表达有很强的相关性，尤其是在腺癌中（P < 0.0001, log rank）。在84对被分析的原发肿瘤和相应的转移灶中HER-2结果的一致性为100%。扩增通常是高水平的，每个肿瘤细胞超过10-15个HER-2拷贝。扩增与生存、分级、pT、pN、pM或UICC分期无关。我们的结论是，食管腺癌属于具有相关频率的高水平HER-2基因扩增的癌症类型，应开展HER-2阳性转移性食管癌对赫赛汀反应的临床试验或个案研究。HER-2在原发性和转移性癌症中的高度一致性表明HER-2阳性原发性肿瘤患者的转移可能对herceptin有反应。
HER-2 is the target for antibody based treatment of breast cancer (Herceptins). In order to evaluate the potential role of such a treatment in esophageal cancers, HER-2 amplification and overexpression was investigated in primary and metastatic cancers of the esophagus. A tissue microarray was constructed from 255 primary esophageal cancers (110 adenocarcinomas and 145 squamous cell carcinomas), 89 nodal and 33 distant metastases. Slides were analyzed by immunohistochemistry (HercepTest (TM); DAKO) and fluorescence in situ hybridization (FISH; PathVysiont; Vysis- Abbott) for HER-2 amplification and overexpression. Amplification was seen in 16/110 (15%) adenocarcinomas and in 7/145 (5%) squamous cell carcinomas. There was a strong association between HER-2 amplification and overexpression, especially in adenocarcinomas (P < 0.0001, log rank). There was a 100% concordance of the HER-2 results in primary tumor and corresponding metastases in 84 analyzed pairs. Amplification was typically high-level with more than 10-15 HER-2 copies per tumor cell. Amplification was unrelated to survival, grading, pT, pN, pM or UICC stage. We conclude that esophageal adenocarcinomas belong to those cancer types with relevant frequency high- level HER-2 gene amplification clinical trials or individual case studies investigating the response of metastatic HER-2-positive esophageal cancers to Herceptins should be undertaken. The strong concordance of the HER-2 status in primary and metastatic cancers argues for a possible response of metastases from patients with HER-2-positive primary tumors to Herceptins.