Tchou Julia, Lam Lian, Li Yun Rose, Edwards Claire, Ky Bonnie, Zhang Hongtao
Division of Endocrine and Oncologic Surgery, Rena Rowan Breast Center, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA.
Department of Pathology and Lab Medicine, University of Pennsylvania Perelman School of Medicine, 3620 Hamilton Walk, Philadelphia, PA 19104 USA.
Springerplus. 2015 May 22;4:237. doi: 10.1186/s40064-015-1015-6. eCollection 2015.
We have developed a new approach to reduce the serum interference for ELISA. The purpose of this study is to investigate if we can use the optimized ELISA (MBB-ELISA) to detect serum soluble HER2/neu (sHER2) in early stage primary breast cancer and monitor its change during treatments.
We collected sera preoperatively from 118 primary breast cancer patients. Serum samples were also collected sequentially from a subset of patients during and after adjuvant treatment. sHER2 in these samples was measured by the MBB-ELISA. Only 16.7 % of tissue HER2 (tHER2) positive patients had significantly elevated sHER2 levels in serum. Interestingly, sera of some patients with tHER2 negative tumors, including those that were 2+ by IHC but negative by FISH, demonstrated slightly elevated sHER2 levels. Multivariate analysis demonstrated that patients with elevated sHER2 (> = 7 ng/ml) had significantly worse disease free survival. During treatments, sHER2 levels consistently fell in response to adjuvant therapies. Nevertheless, in all 4 patients who developed metastases, a steady rise in sHER2 levels was noted before metastatic disease became clinically evident.
For early stage breast cancers, sHER2 is a poor biomarker to predict tHER2 status, but may have value to supplement tissue tests to identify patients with HER2 tumors. Our results also suggest that sHER2 is worth further study as a biomarker to monitor breast cancer patients during treatments.
我们开发了一种新方法来减少酶联免疫吸附测定（ELISA）中的血清干扰。本研究的目的是调查我们是否可以使用优化后的ELISA（MBB-ELISA）来检测早期原发性乳腺癌患者血清中的可溶性HER2/neu（sHER2），并监测其在治疗期间的变化。
我们收集了118例原发性乳腺癌患者术前的血清。还在辅助治疗期间及之后从部分患者中依次采集了血清样本。这些样本中的sHER2通过MBB-ELISA进行检测。只有16.7%的组织HER2（tHER2）阳性患者血清中的sHER2水平显著升高。有趣的是，一些tHER2阴性肿瘤患者的血清，包括那些免疫组化（IHC）为2+但荧光原位杂交（FISH）为阴性的患者，其sHER2水平略有升高。多因素分析表明，sHER2水平升高（≥7 ng/ml）的患者无病生存期明显较差。在治疗期间，sHER2水平随着辅助治疗而持续下降。然而，在所有4例发生转移的患者中，在转移疾病临床显现之前，sHER2水平均出现稳步上升。
对于早期乳腺癌，sHER2作为预测tHER2状态的生物标志物效果不佳，但可能对补充组织检测以识别HER2肿瘤患者具有价值。我们的结果还表明，sHER2作为监测乳腺癌患者治疗期间的生物标志物值得进一步研究。
