• Maximilian Kloft, Jessica E Ruisch, Gayatri Raghuram, Jake Emmerson, Matthew Nankivell, David Cunningham, William H Allum, Ruth E Langley, and Heike I Grabsch.
• Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, Netherlands.
• Ann. Surg. 2023 Feb 1; 277 (2): e320e331e320-e331.

ObjectiveTo 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.BackgroundLymph 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.MethodsThe 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.ResultsLarge 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).ConclusionsThis 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.Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

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