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Tumor budding as an indicator for lymph node metastasis and prognosis of early gastric cancer

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Abstract

Background

Tumor budding, considered as an independent risk factor reflecting prognosis of some malignant tumors, has been recognized as an important clinicopathological indicator of colorectal carcinoma. However, the evaluation of tumor budding and its clinicopathological significance in gastric cancer remain controversial.

Aim

To investigate the relationship between tumor budding and clinical biological behavior of early gastric cancer (EGC) and assess the predictive value of tumor budding for lymph node metastasis as well as its impact on prognosis of EGC patients.

Methods

Tissue specimens of 164 EGC patients who underwent radical gastrectomy between June 2011 and January 2017 from a single center were selected to carry out HE and CK staining respectively, so as to evaluate tumor budding under light microscopy. Clinicopathological data and follow-up results of all EGC patients were collected for statistical analysis among tumor budding, EGC clinicopathological factors and prognosis.

Results

Of all 164 EGC patients, there were 84 (51.2%) cases with mucosal invasion and 80 (48.8%) cases with submucosal invasion. Meanwhile, 32 cases (19.5%) had lymph node metastasis, 19 (11.6%) had lympho-vascular invasion and 4 (2.4%) had early recurrence. Tumor budding were observed in 90 (54.9%) patients, with low-grade budding 68 (41.5%) cases and high-grade budding 22 (13.4%) cases. Tumor budding was closely correlated with tumor size (c2 = 6.609, P = 0.037), tumor histologic differentiation (c2 = 10.522, P = 0.032), depth of invasion (c2 = 8.787, P = 0.012), lymph node metastasis (c2 = 24.226, P < 0.01), TNM stage (c2 = 24.226, P < 0.01), lympho-vascular invasion (c2 = 8.225, P = 0.016) and early recurrence (c2 = 6.462, P = 0.040). Additionally, tumor budding was correlated with postoperative survival rate as well. Multiple regression analysis revealed that tumor budding was an independent influencing factor of postoperative 3-year survival rate, 5-year survival rate, OS, DFS and DSS (P < 0.05). Furthermore, tumor budding was an independent risk factor of lymph node metastasis of EGC patients, and high-grade budding was a high-risk indicator of lymph node metastasis.

Conclusion

Tumor budding is related to tumor size, tumor histologic differentiation, depth of invasion, lymph node metastasis, lympho-vascular invasion and early recurrence of EGC. Tumor budding, especially high-grade budding can serve as an indicator for predicting lymph node metastasis of EGC, and high-grade budding could be an important parameter for evaluating prognosis of EGC patients.

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Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors are grateful to all the patients, researchers, and institutions that participated in the study.

Funding

This work was supported by grants from the Natural Science Foundation of Ningbo (No.2019A610333) and the Medical & Health Science and Technology of Zhejiang Province (No. 2019KY578, 2020KY811 and 2019KY155).

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Authors and Affiliations

  1. The Medical School of Ningbo University, Ningbo, Zhejiang, China

    Gaoyan Yao & Yi Fang

  2. Department of Gastroenterology of The Affiliated People’s Hospital of Ningbo University, No. 251, Baizhang East Road, Yinzhou District, Ningbo, 315000, Zhejiang, China

    Gaoyan Yao

  3. Department of Gastroenterology of Ningbo Yinzhou No.2 Hospital, No. 998, Qianhe Road, Yinzhou District, Ningbo, 315000, Zhejiang, China

    Yi Fang

  4. Department of Gastroenterology of Ningbo First Hospital, No. 59, Liuting Road, Haishu District, Ningbo, 315000, Zhejiang, China

    Yangbo Fu, Haojun Song, Mengli Gu & Xiaoyun Ding

  5. Department of Pathology of The Second Affiliated Hospital of Zhejiang University School of Medicine, No. 88, Jiefang Road, Shangcheng District, Hangzhou, 310000, Zhejiang, China

    Jinghong Xu

  6. Ningbo Clinicopathological Diagnosis Center, No. 685, East Section of Huancheng North Road, Jiangbei District, Ningbo, 315000, Zhejiang, China

    Hangqin Zhu

Authors
  1. Gaoyan Yao
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  2. Yi Fang
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  3. Yangbo Fu
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  6. Hangqin Zhu
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  7. Mengli Gu
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  8. Xiaoyun Ding
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Contributions

XD: contributed to the study conception and design. Material preparation, data collection and analysis were performed by GY, YF and YF, JX, HS, HZ and MG. The first draft of the manuscript was written by GY and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Xiaoyun Ding.

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Conflict of interest

The authors have no financial conflicts of interest.

Ethical approval statement and consent to participate

This study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Human Investigation Committee (IRB) of Ningbo First Hospital approved this study and all participants gave informed consent before taking part. Informed consent was obtained from all individual participants included in the study.

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Yao, G., Fang, Y., Fu, Y. et al. Tumor budding as an indicator for lymph node metastasis and prognosis of early gastric cancer. J Cancer Res Clin Oncol 149, 5603–5616 (2023). https://doi.org/10.1007/s00432-022-04522-z

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  • DOI: https://doi.org/10.1007/s00432-022-04522-z

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