Chen Xianlong, Sun Shanyue, Zhao Jiapeng, Yu Shuangni, Chen Jie, Chen Xinyuan
Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Br J Cancer. 2025 Apr 18. doi: 10.1038/s41416-025-03019-z.
Pathological examination of lymph node metastasis (LNM) is crucial for treating pancreatic ductal adenocarcinoma (PDAC). Although the tumour stroma is correlated with prognosis in multiple solid tumors, its role in detecting LNM in PDAC is unclear. Thus, this study aimed to investigate the relationship of tumor-stroma ratio (TSR) with LNM, survival and mutational profile in PDAC.
In this multicenter retrospective study, we examined molecular and clinicopathologic features of 737 PDAC patients from 5 independent cohorts, including surgically resected and endoscopic ultrasound fine-needle aspiration (EUS-FNA) biopsy specimens. TSR was evaluated on hematoxylin and eosin-stained slides and classified as stroma-low (<50% stroma) or stroma-high (≥50% stroma).
Compared to TSR-high cases, TSR-low cases were significantly associated with LNM (P < 0.001). TSR could accurately distinguish patients with and without LNM with an area under curve (AUC) of 0.749, with the sensitivity and specificity of 76.5% and 71.6%, respectively. This accuracy of TSR for identifying LNM was further increased by adding other factors including PD-L1 expression or pretreatment serum CA19-9 levels. TSR showed similar levels of accuracy in analysis of resected tumor specimens and EUS-FNA biopsies. Moreover, we found that TSR could also identify residual nodal involvement after neoadjuvant therapy (NAT) using pretreatment EUS-FNA biopsy samples. Heterogeneous genetic alterations were observed between TSR-low and TSR-high subgroups. TSR was identified as an independent predictor of LNM and worse disease-free survival. Major findings were all reproducible in validation, EUS-FNA biopsy, and pre-treatment NAT EUS-FNA biopsy cohorts.
TSR served as a robust and reproducible biomarker that identifies patients at risk for LNM. TSR might be used to select treatment and management strategies for PDAC patients.
淋巴结转移（LNM）的病理检查对于治疗胰腺导管腺癌（PDAC）至关重要。尽管肿瘤基质与多种实体瘤的预后相关，但其在检测PDAC中的LNM方面的作用尚不清楚。因此，本研究旨在探讨肿瘤-基质比（TSR）与PDAC中LNM、生存率及突变谱的关系。
在这项多中心回顾性研究中，我们检查了来自5个独立队列的737例PDAC患者的分子和临床病理特征，包括手术切除标本和内镜超声细针穿刺（EUS-FNA）活检标本。在苏木精和伊红染色的玻片上评估TSR，并将其分为基质低（<50%基质）或基质高（≥50%基质）。
与TSR高的病例相比，TSR低的病例与LNM显著相关（P<0.001）。TSR能够准确区分有和无LNM的患者，曲线下面积（AUC）为0.749，敏感性和特异性分别为76.5%和71.6%。通过添加其他因素，包括PD-L1表达或治疗前血清CA19-9水平，TSR识别LNM的准确性进一步提高。TSR在分析切除的肿瘤标本和EUS-FNA活检中显示出相似的准确性水平。此外，我们发现TSR还可以使用治疗前EUS-FNA活检样本识别新辅助治疗（NAT）后残留的淋巴结受累情况。在TSR低和TSR高的亚组之间观察到异质性基因改变。TSR被确定为LNM和较差无病生存率的独立预测因子。主要发现在验证、EUS-FNA活检和治疗前NAT EUS-FNA活检队列中均具有可重复性。
TSR是一种可靠且可重复的生物标志物，可识别有LNM风险的患者。TSR可用于为PDAC患者选择治疗和管理策略。
