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A standardized pathological proposal for evaluating microvascular invasion of hepatocellular carcinoma: a multicenter study by LCPGC

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Abstract

Background and aims

Microvascular invasion (MVI) is a key pathological factor that severely affects the postoperative prognosis of patients with hepatocellular carcinoma (HCC). However, no MVI classification schemes based on standardized gross sampling protocols of HCC are available at present.

Methods

119 HCC specimens were sampled at multiple sites (3-, 7-, and 13 points) for the optimum MVI detection rate. 16,144 resected HCCs were graded as M0, M1 or M2 by adopting three-tiered MVI grading (MVI-TTG) scheme based on the seven-point sampling protocol (SPSP). Survival analyses were performed on 2573 patients to explore the advantages of MVI-TTG.

Results

The MVI detection rate determined by SPSP was significantly higher than that determined by the 3-point sampling method (34.5% vs. 47.1%, p = 0.048), but was similar to that determined by the 13-point sampling method (47.1% vs. 51.3%, p = 0.517). Among 16,144 resected HCCs, the proportions of M0, M1 and M2 specimens according to SPSP were 53.4%, 26.2% and 20.4%, respectively. Postoperative survival analysis in 2573 HCC patients showed that the 3-year recurrence rates in M0, M1 and M2 MVI groups were 62.5%, 71.6% and 86.1%, respectively (p < 0.001), and the corresponding 3-year overall survival (OS) rates were 94.1%, 87.5% and 67.0%, respectively (p < 0.001). M1 grade was associated with early recurrence, while M2 grade was associated with both early and late recurrence. MVI-TTG had a larger area under the curve and net benefit rate than the two-tiered MVI grading scheme for predicting time to recurrence and OS.

Conclusions

SPSP is a practical method to balance the efficacy of sampling numbers and MVI detection rates. MVI-TTG based on SPSP is a better prognostic predictor than the two-tiered MVI scheme. The combined use of SPSP and MVI-TTG is recommended for the routine pathological diagnosis of HCC.

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Acknowledgements

We would like to thank Prof. Han-Lin Wang (Department of Pathology and Laboratory Medicine, University of California at Los Angeles, USA) and Assoc Prof. Xu-Chen Zhang (Department of Pathology, Yale University School of Medicine, USA) for their constructive comments on this article.

Funding

This work is supported by National Natural Science Foundation of China (Grant No. 81472278), Funds for Creative Research Groups of National Natural Science Foundation of China (Grant No. 81521091), and National Key R&D Program of China (Grant No. 2016YFC0902400).

Author information

Author notes

  1. Xia Sheng, Yuan Ji, Guo-Ping Ren, Chang-Li Lu and Jing-Ping Yun first author.

Authors and Affiliations

  1. Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Rd, Shanghai, 200438, China

    Xia Sheng, Han Wang, Qian Zhao & Wen-Ming Cong

  2. Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China

    Yuan Ji

  3. Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Guo-Ping Ren

  4. Department of Pathology, West China Hospital of Sichuan University, Chengdu, China

    Chang-Li Lu

  5. Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China

    Jing-Ping Yun

  6. Department of Pathology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China

    Li-Hong Chen

  7. Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

    Bin Meng

  8. Department of Pathology, The 900Th Hospital of Joint Logistic Support Force, PLA, Fuzhou, China

    Li-Juan Qu

  9. Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Chongqing, China

    Guang-Jie Duan

  10. Department of Pathology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China

    Qing Sun

  11. Department of Pathology, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China

    Xin-Qing Ye

  12. Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Shan-Shan Li

  13. Department of Pathology, Guangzhou First People’s Hospital, Guangzhou, China

    Jing Yang

  14. Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

    Bing Liao

  15. Department of Pathology, The General Hospital of the People’s Liberation Army, Beijing, China

    Zhan-Bo Wang

  16. Department of Pathology, Xiangya Hospital, Central South University, Changsha, China

    Jian-Hua Zhou

  17. Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China

    Yu Sun

  18. Department of Pathology, The First Hospital of China Medical University, Shenyang, China

    Xue-Shan Qiu

  19. Department of Pathology, Fudan University Shanghai Cancer Center, 270 Dong An Rd, Shanghai, 200032, China

    Lei Wang & Xiang Du

  20. Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xian, China

    Zeng-Shan Li

  21. Department of Pathology, Nanjing Drum Tower Hospital, Nanjing, China

    Jun Chen

  22. Department of Pathology, Changzheng Hospital, Shanghai, China

    Chun-Yan Xia

  23. Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, China

    Song He

  24. Department of Pathology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China

    Chuan-Ying Li

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

    En-Wei Xu

  26. Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China

    Jing-Shu Geng

  27. Department of Pathology, Zhongshan Hospital, Xiamen University, Xiamen, China

    Chao Pan

  28. Institute of Pathology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China

    Dong Kuang

  29. Department of Pathology, The Second Hospital of Anhui Medical University, Hefei, China

    Rong Qin

  30. Department of Pathology, The First Affiliated Hospital of Dalian Medical University, Dalian, China

    Hong-Wei Guan

  31. Department of Pathology, Xuzhou Cancer Hospital, Xuzhou, China

    Zhan-Dong Wang

  32. Genome Wisdom Institute, 67 North Fourth Ring West Rd, Beijing, 100800, China

    Li-Xing Li, Xi Zhang, Bo Wei, Wu-Jian Zhang & Shao-Ping Ling

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  1. Xia Sheng
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  2. Yuan Ji
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for the Liver Cancer Pathology Group of China (LCPGC)

Contributions

Concept and design: W-MC, XD, S-PL. Administrative support: W-MC, XD, S-PL. Data collection and acquisition: XS, YJ, G-PR, C-LL, J-PY, L-HC, BM, L-JQ, G-JD, QS, X-QY, S-SL, JY, BL, Z-BW, J-HZ, YS, X-SQ, LW, Z-SL, JC, C-YX, SH, C-YL, E-WX, J-SG, CP, DK, RQ, H-WG, Z-DW, QZ, HW. Data analysis: L-XL, XZ, HW, BW, W-JZ. Writing of article: XS, YJ, HW, W-MC. Final approval of manuscript: all authors

Corresponding authors

Correspondence to Shao-Ping Ling, Xiang Du or Wen-Ming Cong.

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Conflict of interest

There are no conflicts of interest from financial, consulting, institutional or other relationships regarding this manuscript. This study was conducted in accordance with the Declaration of Helsinki and was approved by the Clinical Research Ethics Committees of all participating medical centers. Informed consent was obtained from all patients for their data to be used for research. The patients did not receive financial compensation

Ethical approval

TThis study was conducted in accordance with the Declaration of Helsinki and was approved by the Clinical Research Ethics Committees of all participating medical centers.

Informed consent

Informed consent was obtained from all patients for their data to be used for research. The patients did not receive financial compensation.

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Supplementary Figure 1. Flow chart of the clinicopathological information extraction process. (PDF 131 KB)

12072_2020_10111_MOESM2_ESM.pdf

Supplementary Figure 2. Changes in the detection rate of MVI in HCC tissues before and after using SPSP in the LCPGC. (PDF 7 KB)

Supplementary file3 (DOCX 51 KB)

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Sheng, X., Ji, Y., Ren, GP. et al. A standardized pathological proposal for evaluating microvascular invasion of hepatocellular carcinoma: a multicenter study by LCPGC. Hepatol Int 14, 1034–1047 (2020). https://doi.org/10.1007/s12072-020-10111-4

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