Dear Editor,
We read with great interest the study by Hwang et al. [
1], which showed a retrospective study among hepatocellular carcinoma (HCC) patients with different histologic risk classification of microvascular invasion (MVI) who had undergone liver resection. As we know, MVI is generally defined as the presence of a cluster of tumor cells in microscopic vessels located in the peritumoral liver. They further subclassified MVI according to the number of invaded microvessels (≥5 vs. <5), the presence of muscularized vessel invasion, and the number of invaded tumor cells in the vascular spaces (≥50 vs. <50 cells). In this study, they demonstrated that HCC patients with severe MVI were significantly associated with worse prognosis, while no significant difference in survival was evident between cases of mild MVI and those with no MVI. An increasing number of studies have further noted that different grades of MVI are associated with oncological prognosis, which is different from the classic MVI binary classification of “absent” versus “present” [
1-
3].
A standardized 7-point baseline sampling protocol is widely used in China for pathological diagnosis to evaluate MVI in HCC. The MVI grading system, which specifies the number and location of MVI, is user-friendly for most pathologists and exhibits high repeatability, as well as serves as the cornerstone for comparisons among different groups and individuals [
4]. The severity in the grading of MVI was determined by two experienced pathologists based on the Chinese MVI-TTG system. The grades of MVI severity were classified as follows: M0 (no MVI), M1 (1–5 sites of MVI occurring in the tumor-adjacent liver tissue ≤1.0 cm away from the main tumor), M2 ( >5 sites of MVI occurring in the tumor-adjacent liver tissue ≤1.0 cm, and/or any MVI existing in distant liver tissue >1.0 cm away from the main tumor) [
5]. Based on the MVI-TTG system, they further divided M2 into M2a according to the distance: >5 proximal MVIs (≤1 cm from tumor boundary); M2b: ≥1 distal MVIs (>1 cm from tumor boundary) [
3]. It should be noted that the new MVI-TTG system has a duality in describing the severity of MVI. On the one hand, it can further describe the extent of micrometastasis. On the other hand, if there is an inadequate margin of non-tumoral hepatic parenchymal tissue, it may lead to an underestimation of the degree of MVI grading.
To compare the stratification ability of two different MVI staging systems for HCC. We retrospectively analyzed data from patients with HCC who underwent hepatic resection using a multicenter database. Data were collected from 1,240 patients with solitary HCC at BCLC stage 0/A who underwent hepatectomy between January 1, 2017, and December 31, 2020. We compared OS and time to recurrence (TTR) among HCC patients with different grading severity of MVI. We used the Kaplan-Meier method to compare OS and TTR, and determined the significance of survival and recurrence differences among the three groups using the log-rank test. Cox regression analysis was performed to adjust for potential confounding factors. Patients with M2 were associated with a significantly decreased OS compared to patients with M1 or M0, and there was no statistical difference between patients with M1 and M0 (
Fig. 1A). Similarly, there were significant statistical differences in the survival curve for TTR among the three groups, but not for patients with M1 or M0 (
Fig. 1B). By using multivariable Cox regression to adjust clinicopathological variables, including age (>60 vs. ≤60 years), alpha fetoprotein (>400 vs. ≤400 μg/L), albumin-bilirubin score (>–2.60 vs. ≤–2.60), cirrhosis (presence vs. absence), satellites (presence vs. absence), resection margin (<1 vs. ≥1 cm), tumor differentiation (III/IV vs. ≥ I/II grade), tumor size (>5 vs. ≤5 cm), and tumor encapsulation (incomplete vs. ≤complete), the presence of M2 was an independent risk factor for OS and TTR, while no significant differences in long-term prognosis were evident between cases of M1 and M0. The adjusted hazard ratios were shown in Figure 1A and 1B, respectively.
Although MVI is classified into three grades based on different criteria, the two MVI staging systems for solitary BCLC 0/A patients yield similar results. Recognizing the importance of MVI grading allows for the classification of patients into different risk categories, thereby potentially optimizing clinical decision-making strategies. Aggressive postoperative adjuvant therapies, such as hepatic artery infusion chemotherapy [
6] or immunotherapy [
7], may bring benefits to patients’ long-term prognosis.
FOOTNOTES
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Authors’ contributions
Wei Chen drafted the article. Wei Chen, Yihui Rong, Tianshi Ma, and Weiwei Shi gave substantial contributions to its statistical analysis and data collection. Wei Chen and Hang Jiang revised the manuscript and approved the final version.
-
Conflicts of Interest
The authors have no conflicts to disclose.
Figure 1.Kaplan–Meier survival analysis for overall survival (A) and time to recurrence (B) for the MVI classifications. MVI, microvascular invasion; aHR, adjusted hazard ratios.
Abbreviations
REFERENCES
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