Soltan Maryam, Naimi Azar, Hafez Forghan Razieh, Mansourian Marjan
Department of Pathology, Reproductive Sciences and Sexual Health Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Iran J Pathol. 2025 Spring;20(2):167-172. doi: 10.30699/ijp.2025.2040168.3350. Epub 2025 Mar 10.
BACKGROUND & OBJECTIVE: Breast cancer (BC) can be categorized into 4 groups based on molecular and pathological evidence: Luminal A, Luminal B, HER2+ tumors, and triple-negative breast cancer (TNBC). TNBC has a poorer survival rate and a higher chance of recurrence and metastasis compared to other BC types, primarily due to its challenging treatment course. Claudin 4 (CLDN4), a transmembrane protein in tight junctions between cells, has been linked to poor prognosis and faster disease progression in these malignancies.
Patients previously diagnosed with TNBC and tested for CLDN4 overexpression were contacted for follow-up and to determine disease outcomes. The current health status, cause, and time of death (if applicable) were recorded. Patient files were accessed to obtain information on age, tumor size and grading, lymph node involvement, metastasis, Ki67, and CLDN4 expression.
Patients with high CLDN expression showed a significantly lower mortality rate. However, after controlling for other covariates, the hazard ratio (HR) was 0.48 (95%CI= [0.13 - 1.27]) in the crude model for survival, 0.54 (95%CI = [0.2 - 1.43]) when adjusted for age at diagnosis, and 0.58 (95%CI = [0.18-1.82]) when adjusted for other covariates. CLDN4 was also not correlated with tumor metastasis (HR=0.64, p=0.203, in the crude model; HR=0.52, p=0.409, when adjusted for other covariates). Patients in the CLDN4 high group had a significantly higher number of tumors >2cm.
Although previous studies have shown that CLDN4 overexpression worsens TNBC prognosis and increases metastasis or recurrence, the current study found no such association.
根据分子和病理证据,乳腺癌(BC)可分为4组:腔面A型、腔面B型、HER2+肿瘤和三阴性乳腺癌(TNBC)。与其他BC类型相比,TNBC的生存率较低,复发和转移几率较高,这主要是由于其治疗过程具有挑战性。Claudin 4(CLDN4)是细胞间紧密连接中的一种跨膜蛋白,与这些恶性肿瘤的不良预后和更快的疾病进展有关。
联系先前诊断为TNBC并检测CLDN4过表达的患者进行随访,以确定疾病转归。记录当前健康状况、死因和死亡时间(如适用)。查阅患者档案以获取年龄、肿瘤大小和分级、淋巴结受累情况、转移情况、Ki67和CLDN4表达等信息。
CLDN表达高的患者死亡率显著较低。然而,在控制其他协变量后,生存粗模型中的风险比(HR)为0.48(95%CI = [0.13 - 1.27]),调整诊断年龄后为0.54(95%CI = [0.2 - 1.43]),调整其他协变量后为0.58(95%CI = [0.18 - 1.82])。CLDN4也与肿瘤转移无关(粗模型中HR = 0.64,p = 0.203;调整其他协变量后HR = 0.52,p = 0.409)。CLDN4高表达组中肿瘤>2cm的患者数量显著更多。
尽管先前的研究表明CLDN4过表达会使TNBC预后恶化并增加转移或复发,但本研究未发现此类关联。