Varga Zsuzsanna, Noske Aurelia, Ramach Constanze, Padberg Barbara, Moch Holger
Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
BMC Cancer. 2013 Dec 30;13:615. doi: 10.1186/1471-2407-13-615.
The gold standard of HER2 status assessment in breast cancer is still debated. Immunohistochemistry (IHC) and in-situ technology as fluorescent-labeled methodology (FISH) can be influenced by pre-analytical factors, assay-conditions and interpretation of test results. We retrospectively conducted this quality control study and analyzed HER2 test results in breast cancer within the routine diagnostic service in a single institution over a period of 12 years. We addressed the question how stable and concordant IHC and FISH methods are and whether HER2 positivity rate has changed over this period.
Data of 7714 consecutive HER2-FISH-assays in a period of 12 years (2001-2012) on breast cancer biopsies and excision specimens were retrospectively analyzed. From 2001 to 2004, FISH tests were performed from all cases with IHC score 3+ and 2+ (and in some tumors with IHC score 1+ and 0). From 2005-2010, HER2 status was only determined by FISH. From 2011-2012, all breast carcinomas were analyzed by both IHC and FISH. Scoring and cut-off-definition were done according to time-current ASCO-CAP and FDA-guidelines.
Between 2001-2004, IHC score 3+ was diagnosed in 22% of cases, 69% of these 3+ cases were amplified by FISH. 6% of IHC score 0/1+ cases were amplified by FISH. There was a mean amplification rate of 15.8% (range 13 -19%) using FISH only HER2-assays (2005-2010). Starting 2008, a slight drop in the amplification rate from 17% to 14% was noticed due to the modified ASCO-criteria in 2007. From 2011-2012, 12% of cases were 3+ by IHC, 84% of them were amplified by FISH. Less than 1% of IHC score 0/1+ cases were amplified by FISH. Concordance between FISH and IHC increased from 83% to 97%.
Our quality control study demonstrates that HER2 positivity rate remained stable by FISH-technology but showed a significant variation by IHC over the analyzed 12 years. Improvement in concordance rate was due to standardization of pre-analytical factors, scoring and interpretation.
乳腺癌中HER2状态评估的金标准仍存在争议。免疫组织化学（IHC）和作为荧光标记方法的原位技术（FISH）可能会受到分析前因素、检测条件和检测结果解释的影响。我们回顾性地开展了这项质量控制研究，并分析了一家机构在12年的常规诊断服务中乳腺癌的HER2检测结果。我们探讨了IHC和FISH方法的稳定性和一致性如何，以及在此期间HER2阳性率是否发生了变化。
回顾性分析了2001年至2012年12年间7714例连续的乳腺癌活检和切除标本的HER2-FISH检测数据。2001年至2004年，对所有免疫组化评分为3+和2+的病例（以及一些免疫组化评分为1+和0的肿瘤）进行FISH检测。2005年至2010年，仅通过FISH确定HER2状态。2011年至2012年，所有乳腺癌均通过免疫组化和FISH进行分析。评分和临界值定义根据当时的美国临床肿瘤学会（ASCO）-美国病理学家协会（CAP）和美国食品药品监督管理局（FDA）指南进行。
2001年至2004年，22%的病例免疫组化评分为3+，其中69%的3+病例FISH检测呈扩增。6%的免疫组化评分为0/1+的病例FISH检测呈扩增。仅使用FISH进行HER2检测（2005年至2010年）时，平均扩增率为15.8%（范围为13%-19%）。从2008年开始，由于2007年ASCO标准的修订导致扩增率从17%略有下降至14%。2011年至2012年，12%的病例免疫组化评分为3+，其中84%通过FISH检测呈扩增。免疫组化评分为0/1+的病例中，FISH检测呈扩增的不到1%。FISH和免疫组化之间的一致性从83%提高到了97%。
我们的质量控制研究表明，在分析的12年中，HER2阳性率通过FISH技术保持稳定，但通过免疫组化显示出显著差异。一致性率的提高归因于分析前因素、评分和解释的标准化。
