Microvessel density in hepatocellular carcinoma: Prognostic significance and review of the previous published work

Murakami, Keigo; Kasajima, Atsuko; Kawagishi, Naoki; Ohuchi, Noriaki; Sasano, Hironobu

doi:10.1111/hepr.12487

Cited by 38 publications

(32 citation statements)

References 32 publications

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“…In line with the recently suggested biological mechanism of microvascular invasion, IRE and microvascular invasion are closely related in the present study and several previous studies [30,31]. Taken together, less enhancement of the central portion of the tumor in IRE-HCCs appears to be associated with low microvascular density and a sinusoid-like pattern, which are linked to poor differentiation, frequent microvascular invasion, and poor outcomes in HCC patients [21,25].…”

Section: Discussionsupporting

confidence: 92%

“…One of the pathologic characteristics of IRE-HCCs is the macrotrabecular pattern, which has been demonstrated to be closely correlated with microvascular characteristics and is closely associated with sinusoid-like microvascular patterns and low microvascular density [24,25]. Recently, HCCs with a macrotrabecular pattern were also reported to belong to the S2 signature subclass described by Hoshida and colleagues [18,34], and were correlated with the activation of the YAP oncogene and with the expression of the stemness markers K19 and EpCAM.…”

Section: Discussionmentioning

confidence: 96%

“…The association between microvascular density and enhancement of HCC could be a possible explanation for the IRE-HCC to exhibit a large internal hypoenhancement area. There have been several reports of poorly differentiated HCCs exhibiting arterial phase hypoenhancement and low microvascular density compared to well or moderately differentiated HCCs [25,28]. Sinusoid-like microvascular pattern was also described as "vessels that encapsulate tumor cluster (VETC)" and it has been reported that this particular microvascular pattern could facilitate the microvascular invasion [29].…”

Section: Discussionmentioning

confidence: 99%

“…To study the characteristics of the microvasculature in HCCs, the microvascular patterns and densities were evaluated using CD34 immunostaining [24,25]. The microvascular patterns in HCCs were categorized as follows: (1) [24,25].…”

Section: Histopathology and Immunohistochemistrymentioning

confidence: 99%

“…The microvascular patterns in HCCs were categorized as follows: (1) [24,25]. In cases where both patterns were observed (mixed cases), the proportion of each pattern was recorded.…”

Section: Histopathology and Immunohistochemistrymentioning

confidence: 99%

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Hepatocellular Carcinoma with Irregular Rim-Like Arterial Phase Hyperenhancement: More Aggressive Pathologic Features

Rhee

An²,

Kim

et al. 2018

Liver Cancer

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Background and Aims: The purpose of our study was to examine the histopathologic characteristics of hepatocellular carcinoma (HCC) with irregular rim-like arterial phase enhancement (IRE), which has been reported to be associated with more aggressive tumor behavior. Methods: We investigated 84 pathologically confirmed HCCs in 84 patients who underwent curative hepatic resection after gadoxetate-enhanced magnetic resonance imaging between January 2008 and February 2013. Two abdominal radiologists independently reviewed these images and classified HCCs into two categories: HCC showing IRE (IRE-HCC) and HCC showing hypoenhancement or diffuse arterial enhancement (non-IRE-HCC). Twenty-two HCCs were classified as IRE-HCCs, and 51 were classified as non-IRE-HCCs concordantly by both reviewers. The remaining 11 HCCs, on whose radiologic classifications the reviewers disagreed, were classified as HCCs with intermediate enhancement patterns. The HCC clinicopathologic characteristics and patient outcomes were then compared. Results: IRE-HCCs showed more frequent microvascular invasion (91 vs. 35%), lower microvascular density (246.5 vs. 426.5/mm²), higher proportions of sinusoid-like microvascular pattern (55 vs. 0%) and macrotrabecular pattern (45 vs. 0%), and larger areas of tumor necrosis (15 vs. 0%) and fibrous stroma (8.3 vs. 2.1%) than non-IRE-HCCs. IRE-HCCs also expressed higher levels of immunomarkers of hypoxia (carbonic anhydrase IX, 64 vs. 8%) and stemness (EpCAM, 50 vs. 20%). p values were < 0.001 for all comparisons except for EpCAM (p = 0.026). HCCs with intermediate enhancement patterns showed mixed/intermediate pathologic features from both IRE- and non-IRE-HCCs. IRE-HCC patients showed poorer 5-year disease-free survival after curative resection than non-IRE-HCC patients (p = 0.005). Conclusions: IRE-HCCs demonstrate aggressive histopathologic features, including more hypoxic and fibrotic tumor microenvironments and increased stemness, compared to non-IRE-HCCs. IRE might therefore serve as a noninvasive imaging biomarker for aggressive HCC.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Histopathology and Immunohistochemistrymentioning

confidence: 99%

“…The microvascular patterns in HCCs were categorized as follows: (1) [24,25]. In cases where both patterns were observed (mixed cases), the proportion of each pattern was recorded.…”

Section: Histopathology and Immunohistochemistrymentioning

confidence: 99%

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Hepatocellular Carcinoma with Irregular Rim-Like Arterial Phase Hyperenhancement: More Aggressive Pathologic Features

Rhee

An²,

Kim

et al. 2018

Liver Cancer

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Diagnostic Model for Proliferative HCC Using LI‐RADS: Assessing Therapeutic Outcomes in Hepatectomy and TKI‐ICI Combination

Lu,

Yan,

et al. 2024

Magnetic Resonance Imaging

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BackgroundProliferative hepatocellular carcinoma (HCC), aggressive with poor prognosis, and lacks reliable MRI diagnosis.PurposeTo develop a diagnostic model for proliferative HCC using liver imaging reporting and data system (LI‐RADS) and assess its prognostic value.Study TypeRetrospective.Population241 HCC patients underwent hepatectomy (90 proliferative HCCs: 151 nonproliferative HCCs), divided into the training (N = 167) and validation (N = 74) sets. 57 HCC patients received combination therapy with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs).Field Strength/Sequence3.0 T, T1‐ and T2‐weighted, diffusion‐weighted, in‐ and out‐phase, T1 high resolution isotropic volume excitation and dynamic gadoxetic acid‐enhanced imaging.AssessmentLI‐RADS v2018 and other MRI features (intratumoral artery, substantial hypoenhancing component, hepatobiliary phase peritumoral hypointensity, and irregular tumor margin) were assessed. A diagnostic model for proliferative HCC was established, stratifying patients into high‐ and low‐risk groups. Follow‐up occurred every 3–6 months, and recurrence‐free survival (RFS), progression‐free survival (PFS) and overall survival (OS) in different groups were compared.Statistical TestsFisher's test or chi‐square test, t‐test or Mann–Whitney test, logistic regression, Harrell's concordance index (C‐index), Kaplan–Meier curves, and Cox proportional hazards. Significance level: P < 0.05.ResultsThe diagnostic model, incorporating corona enhancement, rim arterial phase hyperenhancement, infiltrative appearance, intratumoral artery, and substantial hypoenhancing component, achieved a C‐index of 0.823 (training set) and 0.804 (validation set). Median follow‐up was 32.5 months (interquartile range [IQR], 25.1 months) for postsurgery patients, and 16.8 months (IQR: 13.2 months) for combination‐treated patients. 99 patients experienced recurrence, and 30 demonstrated tumor nonresponse. Differences were significant in RFS and OS rates between high‐risk and low‐risk groups post‐surgery (40.3% vs. 65.8%, 62.3% vs. 90.1%, at 5 years). In combination‐treated patients, PFS rates differed significantly (80.6% vs. 7.7% at 2 years).Data ConclusionThe MR‐based model could pre‐treatment identify proliferative HCC and assist in prognosis evaluation.Level of Evidence4.Technical EfficacyStage 2.

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Quantitative free-breathing dynamic contrast-enhanced MRI in hepatocellular carcinoma using gadoxetic acid: correlations with Ki67 proliferation status, histological grades, and microvascular density

Chen

Xia

et al. 2017

Abdom Radiol

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Microvessel density in hepatocellular carcinoma: Prognostic significance and review of the previous published work

Abstract: A low MVD can be used to predict an unfavorable prognosis in HCC patients.

Cited by 38 publications

References 32 publications

Hepatocellular Carcinoma with Irregular Rim-Like Arterial Phase Hyperenhancement: More Aggressive Pathologic Features

Hepatocellular Carcinoma with Irregular Rim-Like Arterial Phase Hyperenhancement: More Aggressive Pathologic Features

Diagnostic Model for Proliferative HCC Using LI‐RADS: Assessing Therapeutic Outcomes in Hepatectomy and TKI‐ICI Combination

Quantitative free-breathing dynamic contrast-enhanced MRI in hepatocellular carcinoma using gadoxetic acid: correlations with Ki67 proliferation status, histological grades, and microvascular density

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