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Immunohistochemical analysis of tumor budding as predictor of lymph node metastasis from superficial esophageal squamous cell carcinoma

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Abstract

Background

Tumor budding is known predictors of lymph node metastasis from esophageal squamous cell carcinoma. However, it is not easy to detect such small cell clusters on hematoxylin–eosin (HE) staining. Therefore, we evaluated tumor budding using immunohistochemistry (IHC) for epithelial cell markers.

Method

We analyzed tumor budding in 50 cases of superficial esophageal squamous cell carcinoma. We evaluated the impact of clinicopathological factors and tumor budding to predict lymph node metastasis. A total of 565 tumor sections were assessed using HE staining and IHC for cytokeratin 5/6.

Results

Based on receiver operating characteristic curves, the cut-off values for high-grade tumor budding evaluated using HE staining or IHC were 2 and 11, respectively. High-grade tumor budding evaluated using HE staining (P = 0.007) and IHC (P ≤ 0.001) were significantly correlated with lymph node metastasis. For tumors with pT1a-MM to pT1b-SM1, high-grade tumor budding evaluated using IHC was correlated with lymph node metastasis (P = 0.050).

Conclusions

Tumor budding was significantly associated with lymph node metastasis. The optimal cut-off values of tumor budding on HE staining and tumor budding on IHC were 2 and 11, respectively. Even though both tumor budding on HE staining and tumor budding on IHC were significantly associated with lymph node metastasis, tumor budding on IHC tend to be more associated with lymph node metastasis.

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Abbreviations

SCC:

Squamous cell carcinoma

SM:

Submucosal layer

MM:

Muscularis mucosae

LPM:

Lamina propria mucosae

HE:

Hematoxylin–eosin

IHC:

Immunohistochemistry

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Acknowledgements

The authors would like to thank Dr. Megumi Wakayama, Dr. Aki Mitsuda, Dr. Kozue Ejima for helpful discussions. We also thank Mr. Minoru Shinozaki for technical assistance.

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Authors and Affiliations

  1. Department of Gastroenterology, School of Medicine, Toho University, Tokyo, Japan

    Kazuhiro Fuchinoue & Yoshinori Igarashi

  2. Department of Clinical Oncology, Graduate School of Medicine, Toho University, Tokyo, Japan

    Kazuhiro Fuchinoue & Hideaki Shimada

  3. Department of Pathology, Showa University Northern Yokohama Hospital, Yokohama, Japan

    Tetsuo Nemoto

  4. Department of Gastroenterological Surgery, School of Medicine, Toho University, Tokyo, Japan

    Hideaki Shimada, Satoshi Yajima, Takashi Suzuki & Yoko Oshima

  5. Department of Surgical Pathology, School of Medicine, Toho University, Tokyo, Japan

    Naobumi Tochigi & Kazutoshi Shibuya

  6. Department of Surgery, Toho University Graduate School of Medicine, Tokyo, Japan

    Hideaki Shimada

Authors
  1. Kazuhiro Fuchinoue
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  2. Tetsuo Nemoto
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  3. Hideaki Shimada
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  4. Naobumi Tochigi
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  5. Yoshinori Igarashi
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  6. Satoshi Yajima
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  7. Takashi Suzuki
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  8. Yoko Oshima
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  9. Kazutoshi Shibuya
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Corresponding author

Correspondence to Hideaki Shimada.

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Ethical Statement

This study was approved by the Toho University Medical Center Omori Hospital Ethics Committee (Approval number: M18015). This retrospective observational study was performed by opt-out method on the web site of the Toho University Omori Medical Center.

Conflict of interest

Dr. Shimada reports grants from TAIHO Pharmaceutical, Co. ltd., grants from Chugai Pharmaceutical, Co. ltd., personal fees from M3/CIWORKS, personal fees from ONO PHARMACEUTICAL CO., LTD., personal fees from Takeda Pharmaceutical Company Limited., grants from Eli Lilly Japan K.K, personal fees from DAIICHI SANKYO HEALTHCARE CO.,LTD., grants and personal fees from Yakult Honsha Co., Ltd., grants from Roche Diagnostics K.K., personal fees from Nippon Kayaku Co, Ltd, personal fees from Oncolys BioPharma Inc., personal fees from EA Pharma Co., Ltd., outside the submitted work;. the other authors have no conflict of interest to declare.

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Fuchinoue, K., Nemoto, T., Shimada, H. et al. Immunohistochemical analysis of tumor budding as predictor of lymph node metastasis from superficial esophageal squamous cell carcinoma. Esophagus 17, 168–174 (2020). https://doi.org/10.1007/s10388-019-00698-5

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  • DOI: https://doi.org/10.1007/s10388-019-00698-5

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