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A new horizon in risk stratification of hepatocellular carcinoma by integrating vessels that encapsulate tumor clusters and microvascular invasion

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Abstract

Background

Vessels that encapsulate tumor clusters (VETC) is a novel described vascular pattern different from microvascular invasion (MVI) for patients with hepatocellular carcinoma (HCC). The prognostic value of integrating VETC and MVI (VETC-MVI model) in HCC patients after resection remains unclear.

Methods

From January 2013 to December 2016, 498 HCC patients who underwent curative resection were enrolled from five academic centers and stratified into different groups according to their VETC and MVI statuses. Overall survival (OS), disease-free survival (DFS), and early and late recurrence rates were evaluated.

Results

The patients were divided into four subgroups: VETC−/MVI− (n = 277, 55.6%), VETC−/MVI+ (n = 110, 22.1%), VETC+/MVI− (n = 53, 10.6%), and VETC+/MVI+ (n = 58, 11.6%). The patients in the VETC+/MVI− and VETC−/MVI+ groups had similar long-term outcomes (OS: p = 0.402; DFS: p = 0.990), VETC−/MVI− patients showed the best prognosis, and VETC+/MVI+ patients had the worst prognosis. Further analysis revealed that the VETC-MVI model showed a similar stratification ability for early recurrence but not for late recurrence. The area under the curve values for early recurrence was 0.70, 0.63 and 0.64 for the VETC-MVI model, VETC, and MVI, respectively (VETC-MVI model vs VETC: p < 0.001; VETC-MVI model vs MVI: p = 0.004; VETC vs MVI: p = 0.539). Multivariate Cox regression analysis showed that the VETC-MVI model successfully predicted OS, DFS and early recurrence.

Conclusions

VETC status provides additional discriminative information for patients with either MVI− or MVI+. A combination of VETC and MVI may help classify subtypes and predict the prognosis of HCC patients.

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Data availability

The data that support the findings of this study are available from the Cancer Center Institutional Data Access/Ethics Committees of the five academic hospitals involved in this study, but restrictions apply to the availability of these data, which were used under license for the current study and so are not publicly available.

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Funding

This study was supported by grants from the Clinical Trials Project (5010 Project) of Sun Yat-sen University (No. 5010–2017009), the Clinical Trials Project (308 Project) of Sun Yat-sen University Cancer Center (No. 308–2015-014), the National Natural Science Foundation of China (No. 81871985), and the Natural Science Foundation of Guangdong Province (No. 2017A030310203).

Author information

Author notes

  1. Lianghe Lu, Wei Wei, Chaoyun Huang and Shaohua Li contributed equally to this study.

Authors and Affiliations

  1. Department of Hepatobiliary Oncology of Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China

    Lianghe Lu, Wei Wei, Shaohua Li, Minshan Chen & Rongping Guo

  2. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China

    Lianghe Lu, Wei Wei, Chaoyun Huang, Shaohua Li, Minshan Chen, Yihong Ling & Rongping Guo

  3. Department of Pathology of Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China

    Chaoyun Huang & Yihong Ling

  4. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou, Guangzhou, People’s Republic of China

    Chong Zhong

  5. Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China

    Jiahong Wang

  6. Department of General Surgery, Dongguan People’s Hospital, Southern Medical University, Dongguan City, Guangdong Province, People’s Republic of China

    Wushen Yu

  7. Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China

    Yongfa Zhang

  8. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China

    Yongfa Zhang

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  1. Lianghe Lu
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Contributions

Acquisition of data: WW, MSC, SHL, CZ, JHW, WSY, and YFZ; Statistical analysi: WW, SHL, CYH, and MSC; Interpretation of results: CYH, CZ, WSY, JHW, and YFZ; Manuscript drafting: LHL, WW, CYH and YHL; Critical revision of the manuscript: LHL, YHL, MSC and RPG; Study concept and design: LHL, YHL, and RPG; All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Yihong Ling or Rongping Guo.

Ethics declarations

Conflict of interest

Lianghe Lu, Wei Wei, Chaoyun Huang, Shaohua Li, Chong Zhong, Jiahong Wang, Wushen Yu, Yongfa Zhang, Minshan Chen, Yihong Ling, Rongping Guo declare no potential conflicts of interest.

Ethics approval

This study was conducted according to the ethical guidelines of the 1975 Declaration of Helsinki and approved by the Institutional Review Board and Human Ethics Committees of the five academic hospitals. All patients gave written informed consent for their archived tissue and clinical data to be used for scientific research in this study.

Informed consent

Informed consent was obtained from all patients for inclusion in the study.

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Supplementary Information

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Supporting Figure 1.

The impacts of VETC and MVI on the long-term outcomes of HCC patients after resection in the entire cohort. VETC: (A) Overall survival; (B) Disease-free survival; (C) Early recurrence; (D) Late recurrence. MVI: (E) Overall survival; (F) Disease-free survival; (G) Early recurrence; (H) Late recurrence. (TIF 1584 kb)

Supporting Figure 2.

The impact of the VETC-MVI model on the long-term outcomes of HCC patients after resection in the SYSUCC cohort: (A) Overall survival. (B) Disease-free survival. (C) Early recurrence. (D) Late recurrence. In addition, the GTFD cohort: (E) Overall survival. (F) Disease-free survival. (G) Early recurrence. (H) Late recurrence. (TIF 2168 kb)

Supporting

Figure 3. Subgroup analysis of the VETC-MVI model on the long-term outcomes of patients after resection in the entire cohort. Tumor size<5 cm: (A) Overall survival; (B) Disease-free survival. Tumor size ≥5 cm: (C) Overall survival; (D) Disease-free survival. Solitary tumor: (E) Overall survival; (F) Disease-free survival. Multiple tumors: (G) Overall survival; (H) Disease-free survival. MTM-positive: (I) Overall survival; (J) Disease-free survival. MTM-negative: (K) Overall survival; (L) Disease-free survival. (TIF 1811 kb)

S

upporting Figure 4. The prognostic value of integrating the VETC and MVI grading systems. MVI grading system: (A) Overall survival; (B) Disease-free survival. Combination of VETC and MVI grading system: (C) Overall survival; (B) Disease-free survival. (TIF 638 kb)

Supplementary file5 (DOCX 21 kb)

Supplementary file6 (DOCX 19 kb)

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Lu, L., Wei, W., Huang, C. et al. A new horizon in risk stratification of hepatocellular carcinoma by integrating vessels that encapsulate tumor clusters and microvascular invasion. Hepatol Int 15, 651–662 (2021). https://doi.org/10.1007/s12072-021-10183-w

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  • DOI: https://doi.org/10.1007/s12072-021-10183-w

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