Gheni Nadia, Westenberg David
Department of Pathology and Forensic Medicine, College of Medicine, Tikrit University, Iraq.
Department of Biology, Missouri University of Science and Technology, USA.
Indian J Pathol Microbiol. 2020 Feb;63(Supplement):S123-S128. doi: 10.4103/IJPM.IJPM_136_19.
Human epidermal growth factor receptor HER2/neu status is an important prognostic factor for breast cancer as it is crucial in stimulating growth and cellular motility. Overexpression of HER2/neu is observed in 10%-35% of the human breast cancer and is associated with prognosis and response to treatment. The magnitude of amplification must be determined to facilitate better prognosis and personalized therapy in the affected patient. This study aims to investigate the HER2/neu status in breast cancer by concurrent HER2/neu protein overexpression immunohistochemically with HER2/neu DNA amplification by quantitative real-time polymerase chain reaction (PCR), allowing accurate and precise quantification of HER2/neu amplification after a follow-up period. A total of 54 paired tissue samples from formalin-fixed paraffin-embedded (FFPE) breast cancer patients enrolled in this study were collected to evaluate tumor and normal tissues. Only cases with 80% and more tumor cells were included. For confirmation of immunohistochemistry (IHC) results, qPCR was used to determine the HER2/neu amplification. The association between clinicopathological variables like age, tumor size, histological grade, stage, lymph node status, hormone receptor status, family history, recurrence rate, and vital status was evaluated. We observed that 11/54 (20.4%) of the tumor tissues are positive for HER2/neu protein overexpression by IHC. A total of 8 out of these 11 cases (72.7%), which presented a score of 3+, showed gene amplification of HER2/neu. The concordance rate between IHC and qPCR was 94.4%. HER2/neu gene amplification was found to be significantly associated with recurrence, increased risk of death, and progesterone receptor status, supporting a negative prognostic role of HER2/neu in breast cancer survival. In conclusion, IHC can be used as an initial screening test to detect HER2/neu protein overexpression, and the use of qPCR can verify the IHC results and establish HER2/neu status in routine clinical practice.
人表皮生长因子受体HER2/neu状态是乳腺癌的一个重要预后因素，因为它在刺激生长和细胞运动方面至关重要。在10%-35%的人类乳腺癌中观察到HER2/neu过表达，且其与预后及治疗反应相关。必须确定扩增程度，以便为受影响患者实现更好的预后和个性化治疗。本研究旨在通过免疫组织化学法同时检测HER2/neu蛋白过表达以及通过定量实时聚合酶链反应（PCR）检测HER2/neu DNA扩增，来研究乳腺癌中的HER2/neu状态，从而在随访期后对HER2/neu扩增进行准确且精确的定量。本研究收集了54例来自参与研究的福尔马林固定石蜡包埋（FFPE）乳腺癌患者的配对组织样本，以评估肿瘤组织和正常组织。仅纳入肿瘤细胞占80%及以上的病例。为确认免疫组织化学（IHC）结果，采用qPCR来确定HER2/neu扩增情况。评估了年龄、肿瘤大小、组织学分级、分期、淋巴结状态、激素受体状态、家族史、复发率和生存状态等临床病理变量之间的关联。我们观察到，通过IHC检测，11/54（20.4%）的肿瘤组织HER2/neu蛋白过表达呈阳性。在这11例病例中，共有8例（72.7%）评分为3+，显示HER2/neu基因扩增。IHC与qPCR之间的一致性率为94.4%。发现HER2/neu基因扩增与复发、死亡风险增加以及孕激素受体状态显著相关，这支持了HER2/neu在乳腺癌生存中具有负面预后作用。总之，IHC可作为检测HER2/neu蛋白过表达的初始筛查试验，在常规临床实践中，使用qPCR可验证IHC结果并确定HER2/neu状态。
