Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, Netherlands.
Division of Pathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.
Ann Surg. 2023 Feb 1;277(2):e320-e331. doi: 10.1097/SLA.0000000000005214. Epub 2023 Jan 10.
To analyze the relationship between negative lymph node (LNneg) size as a possible surrogate marker of the host antitumor immune response and overall survival (OS) in esophageal cancer (EC) patients.
Lymph node (LN) status is a well-established prognostic factor in EC patients. An increased number of LNnegs is related to better survival in EC. Follicular hyperplasia in LNneg is associated with better survival in cancer-bearing mice and might explain increased LN size.
The long axis of 304 LNnegs was measured in hematoxylin-eosin stained sections from resection specimens of 367 OE02 trial patients (188 treated with surgery alone (S), 179 with neoadjuvant chemotherapy plus surgery (C+S)) as a surrogate of LN size. The relationship between LNneg size, LNneg microarchitecture, clinicopathological variables, and OS was analyzed.
Large LNneg size was related to lower pN category ( P = 0.01) and lower frequency of lymphatic invasion ( P = 0.02) in S patients only. Irrespective of treatment, (y)pN0 patients with large LNneg had the best OS. (y)pN1 patients had the poorest OS irrespective of LNneg size ( P < 0.001). Large LNneg contained less lymphocytes ( P = 0.02) and had a higher germinal centers/lymphocyte ratio ( P = 0.05).
This is the first study to investigate LNneg size in EC patients randomized to neoadjuvant chemotherapy followed by surgery or surgery alone. Our pilot study suggests that LNneg size is a surrogate marker of the host antitumor immune response and a potentially clinically useful new prognostic biomarker for (y)pN0 EC patients. Future studies need to confirm our results and explore underlying biological mechanisms.
分析食管癌（EC）患者中阴性淋巴结（LNneg）大小作为宿主抗肿瘤免疫反应替代标志物与总生存期（OS）之间的关系。
淋巴结（LN）状态是 EC 患者预后的一个既定因素。LNnegs 数量增加与 EC 患者生存改善相关。LNneg 滤泡增生与荷瘤小鼠生存改善相关，并可能解释 LN 增大的原因。
在 OE02 试验 367 例患者（188 例单独接受手术治疗（S），179 例接受新辅助化疗加手术治疗（C+S））的切除标本苏木精-伊红染色切片中测量 304 个 LNneg 的长轴，作为 LN 大小的替代指标。分析 LNneg 大小、LNneg 微观结构、临床病理变量与 OS 之间的关系。
S 组患者中，较大的 LNneg 大小与较低的 pN 分期（P = 0.01）和较低的淋巴管侵犯频率（P = 0.02）相关。无论治疗方式如何，（y）pN0 患者中 LNneg 较大者 OS 最佳。（y）pN1 患者中 LNneg 大小与 OS 最差（P < 0.001）。较大的 LNneg 中淋巴细胞较少（P = 0.02），生发中心/淋巴细胞比值较高（P = 0.05）。
这是第一项针对接受新辅助化疗后行手术或单纯手术治疗的 EC 患者进行 LNneg 大小研究的试验。我们的初步研究表明，LNneg 大小是宿主抗肿瘤免疫反应的替代标志物，可能是（y）pN0 EC 患者的一种有潜在临床应用价值的新预后生物标志物。未来的研究需要验证我们的结果并探索潜在的生物学机制。
