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Tumor infiltrative growth pattern correlates with the immune microenvironment and is an independent factor for lymph node metastasis and prognosis in stage T1 esophageal squamous cell carcinoma

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Abstract

In this retrospective study, we analyzed the association between the tumor infiltrative growth pattern (INF) and tumor immune environment and its predictive value for lymph node metastasis and overall survival (OS) in stage T1 esophageal squamous cell carcinoma (ESCC). In total, 593 patients with a diagnosis of stage T1 ESCC who underwent esophagectomy and regional lymphadenectomy between 2009 and 2018 were included. The INF type and elements of the tumor immune microenvironment, including tumor infiltrative lymphocytes (TILs) and tertiary lymphoid structures (TLSs), were microscopically evaluated within the tumor invasive margin with hematoxylin and eosin (HE)-stained slices. The infiltrative-type INF (INFc) was associated with low-grade TILs and the absence of TLSs, deep tumor invasion, poorly differentiated phenotype. Multivariate logistic regression identified INFc as one of the independent risk factors for lymph node metastasis. INFc and low-grade TILs were independent inferior predictive factors for OS. A novel histologic risk stratification model was classified as INFa/b and high-grade TILs, INFa/b and low-grade TILs, INFc and high-grade TILs, and INFc and low-grade TILs. The Kaplan-Meier curves showed that INFa/b and high-grade TILs were associated with the best prognosis, and INFc and low-grade TILs were associated with the worst prognosis, and there was significant difference between groups. In conclusion, INFc is an independent risk factor for lymph node metastasis and an independent inferior prognostic factor for stage T1 ESCC. Furthermore, INFc is associated with immunosuppression, and the combination of the INF and TILs is useful for the risk stratification of prognosis.

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Authors and Affiliations

  1. Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

    Yuanyuan Zhao, Hong Chen, Ying Wang & Mulan Jin

  2. Department of Pathology, Shanxi Cancer Hospital, Taiyuan, China

    Yuanyuan Zhao, Enwei Xu & Xuanqin Yang

  3. Department of Gastroenterology, Shanxi Cancer Hospital, Taiyuan, China

    Yong Zhang

Authors
  1. Yuanyuan Zhao
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  2. Enwei Xu
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  3. Xuanqin Yang
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  4. Yong Zhang
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  5. Hong Chen
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  6. Ying Wang
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  7. Mulan Jin
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Contributions

Jin Mulan, Chen Hong, and Wang Ying conceived and designed the study, and revised the manuscript. Zhang Yong acquired clinical data and revised the manuscript. Xu Enwei, Yang Xuanqin, and Zhao Yuanyuan evaluated histological findings. Zhao Yuanyuan integrated the data, performed the statistical analysis, and wrote the manuscript. All authors approved the final manuscript for submission.

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Correspondence to Mulan Jin.

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The authors declare that they have no conflict of interest.

Ethical approval

This study was conducted with the approval of the ethics committee of the Shanxi cancer hospital, China (Reference number 201990).

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This article is part of the Topical Collection on Quality in Pathology

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Zhao, Y., Xu, E., Yang, X. et al. Tumor infiltrative growth pattern correlates with the immune microenvironment and is an independent factor for lymph node metastasis and prognosis in stage T1 esophageal squamous cell carcinoma. Virchows Arch 477, 401–408 (2020). https://doi.org/10.1007/s00428-020-02801-z

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  • DOI: https://doi.org/10.1007/s00428-020-02801-z

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