Gómez-Archila José Damián, Espinosa-García Ana María, Palacios-Reyes Carmen, Trujillo-Cabrera Yanelly, Mejía Ana Lilia Sandoval, González Ana Victoria De Alba, Rangel-López Edgar, Alonso-Themann Patricia García, Solís Nereo Damaso Sandoval, Hernández-Zavala Araceli, López Pedro Grajeda, Contreras-Ramos Alejandra, Palma-Lara Icela
Sección de Estudios de Posgrado, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Colonia Santo Tomás, Ciudad de México 11340, Mexico; Servicio de Oncología Quirúrgica, Servicio de Patología, Hospital de Gineco-Obstetricia No.3, IMSS, Centro Médico La Raza, Ciudad de México, Mexico.
Servicio de Farmacología Clínica, Hospital General de México, Ciudad de México, Mexico.
Am J Med Sci. 2022 Nov;364(5):583-594. doi: 10.1016/j.amjms.2021.12.015. Epub 2022 May 1.
In regards to breast cancer (BC), survival or disease-free periods are still compromised mainly in Triple Negative (TN) and HER2 tumors. The participation of estrogen receptor (ER) has been reported as crucial in the signaling pathways, including the NOTCH pathway. The study was aimed to evaluate the expression of NOTCH1 and NOTCH3 in BC and its relationship with the presence of ER, as well as with relapses.
NOTCH1 and NOTCH3 expression was evaluated in BC using Oncomine database, Breast Cancer Gene Expression Miner database and Kaplan Meier Plotter. Subsequently, detection of NOTCH1 and NOTCH3 in 100 paraffin-embedded BC samples from Mexican patients was achieved by immunohistochemistry (IHC) and RT-qPCR, a group of benign breast tumors were included as controls. Relapses were evaluated by BC subtypes and their relationship with NOTCH1 and NOTCH3 expression, as well as with ER expression.
The analyses from public databases of TN and HER2 groups, which are estrogen receptor-negative (ERN), revealed NOTCH1 and NOTCH3 expression variability. The overexpression was associated with lower relapse-free survival (P = 0.00019). These data were concordant with results from tumor samples of patients included in this study, which showed overexpression of NOTCH1 and NOTCH3 in ERN tumors, as well as lower relapse-free survival (P < 0.0001).
NOTCH1 and NOTCH3 were found to be overexpressed mainly in ERN tumors. HER2 and TN groups, are related to higher relapse rates. Therefore, anti-NOTCH therapy could be justified and implemented in conventional treatments of high-risk BC groups.
关于乳腺癌（BC），三阴型（TN）和人表皮生长因子受体2（HER2）型肿瘤的生存期或无病期仍然受到影响。据报道，雌激素受体（ER）在包括NOTCH通路在内的信号通路中起关键作用。本研究旨在评估NOTCH1和NOTCH3在乳腺癌中的表达及其与ER的存在以及复发的关系。
使用Oncomine数据库、乳腺癌基因表达挖掘器数据库和Kaplan Meier绘图仪评估乳腺癌中NOTCH1和NOTCH3的表达。随后，通过免疫组织化学（IHC）和逆转录定量聚合酶链反应（RT-qPCR）检测了100例来自墨西哥患者的石蜡包埋乳腺癌样本中的NOTCH1和NOTCH3，纳入一组良性乳腺肿瘤作为对照。通过乳腺癌亚型评估复发情况及其与NOTCH1和NOTCH3表达以及ER表达的关系。
对雌激素受体阴性（ERN）的TN和HER2组公共数据库的分析显示NOTCH1和NOTCH3表达存在变异性。过表达与较低的无复发生存率相关（P = 0.00019）。这些数据与本研究中患者肿瘤样本的结果一致，该结果显示ERN肿瘤中NOTCH1和NOTCH3过表达，以及较低的无复发生存率（P < 0.0001）。
发现NOTCH1和NOTCH3主要在ERN肿瘤中过表达。HER2和TN组与较高的复发率相关。因此，抗NOTCH治疗在高危乳腺癌组的常规治疗中可能是合理的并可实施。
