Yes相关蛋白1(YAP1)表达模式在局部晚期乳腺癌中的影响:与病理反应和肿瘤特征的关联
The Impact of Yes-Associated Protein 1 (YAP1) Expression Patterns in Locally Advanced Breast Cancer: Associations with Pathological Response and Tumor Features.
作者信息
Erinc Osman, Goktas Aydin Sabin, Erkinuresin Taskin, Yilmaz Ozgur, Aydin Ahmet, Dagistanli Sevinc, Akarsu Murat
机构信息
Department of Internal Medicine, Kanuni Sultan Suleyman Training and Research Hospital, 34303 Istanbul, Turkey.
Department of Medical Oncology, Kanuni Sultan Suleyman Training and Research Hospital, 34303 Istanbul, Turkey.
出版信息
Medicina (Kaunas). 2025 Jul 18;61(7):1297. doi: 10.3390/medicina61071297.
: The Hippo pathway, via Yes-associated protein 1 (YAP1), regulates cell proliferation, apoptosis, and tissue regeneration. Aberrant YAP1 activation is linked to tumor progression and immune evasion in various cancers, including breast carcinoma, despite conflicting evidence on its prognostic value. Preclinical studies have explored drugs targeting YAP1-TEAD interactions, but therapeutic application is limited. : This study included 50 patients with locally advanced breast cancer, who were assessed by a multidisciplinary tumor board and underwent neoadjuvant treatment per tumor subtype and clinical guidelines. Eligibility required both pre-treatment core biopsy and post-treatment surgical resection samples. Due to the absence of residual tumor in some patients achieving complete pathological response, post-treatment tissue was available and analyzable in 30 patients. YAP1 expression was evaluated immunohistochemically for nuclear and cytoplasmic staining patterns. ROC analysis identified a cutoff for YAP1 expression, defining tumors with ≥70% nuclear and ≥80% cytoplasmic staining. : YAP1 expression had a significant relationship with tumor subtype ( = 0.001), being most frequent in HER-2-positive tumors (55.6%) and least frequent in luminal tumors (11.1%). YAP1 positivity significantly predicted axillary pathological complete response (pCR) ( = 0.01). In YAP1-positive patients, 77.8% achieved axillary pCR compared to 31.7% in YAP1-negative patients, though the YAP1 status and breast pCR association were insignificant ( = 0.07). The Mann-Whitney U test indicated that higher Ki-67 values were significantly associated with positive YAP1 expression ( = 0.028). In contrast, there was no association between ER, PR status, age, and tumor size. Following treatment, there was a statistically significant change in YAP1 expression, with nuclear staining decreasing ( = 0.004) while cytoplasmic staining increased ( = 0.002). YAP1 was significantly linked to axillary pCR, HER-2 status, and Ki-67. : Post treatment, nuclear YAP1 decreased, whereas cytoplasmic expression increased, showing a localization shift. These results suggest that YAP1 may predict treatment response and become a future therapeutic target.
河马通路通过Yes相关蛋白1(YAP1)调节细胞增殖、凋亡和组织再生。尽管关于YAP1的预后价值存在相互矛盾的证据,但YAP1的异常激活与包括乳腺癌在内的多种癌症的肿瘤进展和免疫逃逸有关。临床前研究已经探索了靶向YAP1-TEAD相互作用的药物,但治疗应用有限。
本研究纳入了50例局部晚期乳腺癌患者,这些患者由多学科肿瘤委员会进行评估,并根据肿瘤亚型和临床指南接受新辅助治疗。入选要求有治疗前的核心活检和治疗后的手术切除样本。由于一些达到完全病理缓解的患者没有残留肿瘤,因此30例患者有治疗后的组织可供分析。通过免疫组织化学评估YAP1表达的核染色和胞质染色模式。ROC分析确定了YAP1表达的临界值,定义核染色≥70%且胞质染色≥80%的肿瘤。
YAP1表达与肿瘤亚型有显著关系(P = 0.001),在HER-2阳性肿瘤中最常见(55.6%),在管腔型肿瘤中最不常见(11.1%)。YAP1阳性显著预测腋窝病理完全缓解(pCR)(P = 0.01)。在YAP1阳性患者中,77.8%达到腋窝pCR,而YAP1阴性患者为31.7%,尽管YAP1状态与乳腺pCR的关联不显著(P = 0.07)。Mann-Whitney U检验表明,较高的Ki-67值与YAP1阳性表达显著相关(P = 0.028)。相比之下,ER、PR状态、年龄和肿瘤大小之间没有关联。治疗后,YAP1表达有统计学显著变化,核染色减少(P = 0.004),而胞质染色增加(P = 0.002)。YAP1与腋窝pCR、HER-2状态和Ki-67显著相关。
治疗后,核YAP1减少,而胞质表达增加,显示出定位转移。这些结果表明,YAP1可能预测治疗反应并成为未来的治疗靶点。