Department of Surgery, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands.
Ann Oncol. 2013 May;24(5):1290-7. doi: 10.1093/annonc/mds640. Epub 2013 Jan 18.
In esophageal adenocarcinoma (EAC), concordance and prognostic significance of human epidermal growth factor 2 (HER-2) protein overexpression and gene amplification are equivocal, which led us to reevaluate this by immunohistochemistry (IHC) and in situ hybridization.
One hundred and fifty-four patients were included in a tissue micro array (TMA). HER-2 gene amplification was assessed by fluorescence and silver-enhanced in situ hybridization (FISH and SISH) and expression with the HercepTest™.
HER-2 was amplified in 16% by SISH and 18% by FISH. HER-2 positivity (IHC 3+ or 2+ with ISH+) was seen in 12% and overexpression (IHC 2+/3+) in 14%. Concordance was 92% between SISH/IHC, 90% between FISH/IHC and 95% between SISH/FISH. All IHC 3+ cases were amplified by SISH and in 93% by FISH. Of the IHC 2+cases, this was 33% (SISH) and 50% (FISH). Of the IHC 1+ cases, still 6% (SISH) and 8% (FISH) showed amplification. HER-2 positivity, overexpression and amplification were all associated with poor cancer-specific survival, in univariate analysis. Furthermore, HER-2 positivity and amplification (SISH) were independently associated with poor survival (hazard ratio, HR 6.343; 95% CI 1.218-36.234; P = 0.029 and HR 3.231; 95% CI 1.092-9.563; P = 0.034).
HER-2 positivity and gene amplification are fairly frequent and independently associated with poor survival.
在食管腺癌（EAC）中，人表皮生长因子 2（HER-2）蛋白过表达和基因扩增的一致性和预后意义尚不确定，这促使我们通过免疫组织化学（IHC）和原位杂交技术重新评估这一点。
154 例患者纳入组织微阵列（TMA）。通过荧光原位杂交（FISH）和银增强原位杂交（SISH）评估 HER-2 基因扩增，并用 HercepTest™检测表达。
SISH 检测到 16%的 HER-2 扩增，FISH 检测到 18%的 HER-2 扩增。IHC 3+或 2+且 ISH+阳性（IHC 3+或 2+且 ISH+阳性）占 12%，过表达（IHC 2+/3+）占 14%。SISH/IHC 之间的一致性为 92%，FISH/IHC 之间的一致性为 90%，SISH/FISH 之间的一致性为 95%。所有 IHC 3+病例均经 SISH 扩增，93%经 FISH 扩增。IHC 2+病例中，SISH 为 33%，FISH 为 50%。IHC 1+病例中，仍有 6%（SISH）和 8%（FISH）显示扩增。在单因素分析中，HER-2 阳性、过表达和扩增均与癌症特异性生存不良相关。此外，HER-2 阳性和扩增（SISH）与不良生存独立相关（危险比，HR 6.343；95%CI 1.218-36.234；P=0.029 和 HR 3.231；95%CI 1.092-9.563；P=0.034）。
HER-2 阳性和基因扩增相当常见，与不良生存独立相关。
