Boldrin Elisa, Mazza Marcodomenico, Piano Maria Assunta, Alfieri Rita, Montagner Isabella Monia, Magni Giovanna, Scaini Maria Chiara, Vassallo Loretta, Rosato Antonio, Pilati Pierluigi, Scapinello Antonio, Curtarello Matteo
Immunology and Molecular Oncology, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padova, Italy.
Surgical Oncology of the Esophagus and Digestive Tract Unit, Veneto Institute of Oncology IOV-IRCCS, Via dei Carpani 16, 31033 Castelfranco Veneto, Italy.
Cancers (Basel). 2022 Apr 27;14(9):2180. doi: 10.3390/cancers14092180.
Anti-HER2 monoclonal antibody trastuzumab improves the survival of those patients with advanced gastroesophageal adenocarcinoma (GEA) exhibiting HER2/ overexpression/amplification. The current gold standard methods used to diagnose the HER2 status in GEA are immunohistochemistry (IHC) and silver or fluorescence in situ hybridization (SISH or FISH). However, they do not permit spatial and temporal tumor monitoring, nor do they overcome intra-cancer heterogeneity. Droplet digital PCR (ddPCR) was used to implement the assessment of HER2 status in formalin-fixed paraffin-embedded (FFPE) tumor DNA from a retrospective cohort (86 patients) and in cell-free DNA (cfDNA) samples from a prospective cohort (28 patients). In comparison to IHC/SISH, ddPCR assay revealed amplification in a larger patient fraction, including HER2 2+ and 0-1+ of the retrospective cohort (45.3% vs. 15.1%). In addition, a considerable number of HER2 2+ and 0-1+ prospective patients who were negative in FFPE by both IHC/SISH and ddPCR, showed amplification in the cfDNA collected just before surgery. cfDNA analysis in a few longitudinal cases revealed an increasing trend at progression. In conclusion, ddPCR in liquid biopsy may improve the detection rate of HER2 positive patients, preventing those patients who could benefit from targeted therapy from being incorrectly excluded.
抗HER2单克隆抗体曲妥珠单抗可提高那些HER2过表达/扩增的晚期胃食管腺癌（GEA）患者的生存率。目前用于诊断GEA中HER2状态的金标准方法是免疫组织化学（IHC）以及银染或荧光原位杂交（SISH或FISH）。然而，它们无法进行肿瘤的时空监测，也不能克服肿瘤内的异质性。采用液滴数字PCR（ddPCR）对来自一个回顾性队列（86例患者）的福尔马林固定石蜡包埋（FFPE）肿瘤DNA以及来自一个前瞻性队列（28例患者）的游离DNA（cfDNA）样本进行HER2状态评估。与IHC/SISH相比，ddPCR检测显示在更大比例的患者中存在扩增，包括回顾性队列中HER2 2+和0-1+的患者（45.3%对15.1%）。此外，相当数量的HER2 2+和0-1+前瞻性患者通过IHC/SISH和ddPCR在FFPE中均为阴性，但在术前采集的cfDNA中显示出扩增。少数纵向病例的cfDNA分析显示，病情进展时呈上升趋势。总之，液体活检中的ddPCR可能提高HER2阳性患者的检测率，避免那些可能从靶向治疗中获益的患者被错误排除。
