Microvessel Density In Hepatocellular Carcinoma Research Articles

Correlation of radiomic features on dynamic contrast-enhanced magnetic resonance with microvessel density in hepatocellular carcinoma based on different models.

ObjectiveTo explore the correlations of radiomic features of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with microvessel density (MVD) in patients with hepatocellular carcinoma (HCC), based on single-input and dual-input two-compartment extended Tofts (SITET and DITET) models.MethodsWe compared the quantitative parameters of SITET and DITET models for DCE-MRI in 30 patients with HCC using paired sample t-tests. The correlations of SITET and DITET model parameters with CD31-MVD and CD34-MVD were analyzed using Pearson’s correlation analysis. A diagnostic model of CD34-MVD was established and the diagnostic abilities of models for MVD were analyzed using receiver operating characteristic curve (ROC) analysis.ResultsThere were significant differences between the quantitative parameters in the two kinds of models. Compared with SITET, DITET parameters showed better correlations with CD31-MVD and CD34-MVD. The Ktrans and Ve radiomics features of the DITET model showed high efficiency for predicting the level of CD34-MVD according to ROC analysis, with areas under curves of 0.83 and 0.94, respectively.ConclusionCompared with SITET, the DITET model provides a better indication of the microcirculation of HCC and is thus more suitable for examining patients with HCC.

Preoperative normalized iodine concentration derived from spectral CT is correlated with early recurrence of hepatocellular carcinoma after curative resection.

To investigate whether normalized iodine concentration (NIC) correlates with tumor microvessel density and early recurrence in patients with HCC. We included 71 patients with surgically resected single HCC in this prospective study who underwent preoperative spectral CT between November 2014 and June 2016. Two observers independently measured the NIC in the arterial phase (AP) and portal venous phase (PVP). The relationship between NIC and microvessel density was evaluated. Univariate and multivariate logistic regression was performed to evaluate independent predictors of early recurrence. Early recurrence occurred in 28 of 71 patients (39.4%) during the 2-year follow-up. NIC-AP positively correlated with microvessel density for the two observers (r = 0.593 and 0.527). Based on multivariate analysis, independent risk factors for early HCC recurrence were tumor size (odds ratio, 1.200; p = 0.043) and NIC-AP (odds ratio, 2.522; p = 0.005). For the two observers, areas under the receiver operating characteristic curve for predicting early HCC recurrence were 0.719 and 0.677. Early recurrence rates were significantly higher among patients with NIC-AP values higher than the optimal cutoff than among those with values below the cutoff. Normalized iodine concentration in the arterial phase from spectral CT reflects tumor-derived angiogenesis and is a potential predictive biomarker for early recurrence of hepatocellular carcinoma. • Normalized iodine concentration in the arterial phase positively correlated with microvessel density of hepatocellular carcinoma. • In the patients with hepatocellular carcinoma, tumor size and normalized iodine concentration in the arterial phase were independent risk factors for early hepatocellular carcinoma recurrence. • Early hepatocellular carcinoma recurrence rates were significantly higher when normalized iodine concentration in the arterial phase values was above the optimal cutoff.

Whole Slide Imaging for Analytical Anatomic Pathology and Telepathology: Practical Applications Today, Promises, and Perils.

Whole slide imaging (WSI) offers a convenient, tractable platform for measuring features of routine and special-stain histology or in immunohistochemistry staining by using digital image analysis (IA). We now routinely use IA for quantitative and qualitative analysis of theranostic markers such as human epidermal growth factor 2 (HER2/neu), estrogen and progesterone receptors, and Ki-67. Quantitative IA requires extensive validation, however, and may not always be the best approach, with pancreatic neuroendocrine tumors being one example in which a semiautomated approach may be preferable for patient care. We find that IA has great utility for objective assessment of gastrointestinal tract dysplasia, microvessel density in hepatocellular carcinoma, hepatic fibrosis and steatosis, renal fibrosis, and general quality analysis/quality control, although the applications of these to daily practice are still in development. Collaborations with bioinformatics specialists have explored novel applications to gliomas, including in silico approaches for mining histologic data and correlating with molecular and radiologic findings. We and many others are using WSI for rapid, remote-access slide reviews (telepathology), though technical factors currently limit its utility for routine, high-volume diagnostics. In our experience, the greatest current practical impact of WSI lies in facilitating long-term storage and retrieval of images while obviating the need to keep slides on site. Once the existing barriers of capital cost, validation, operator training, software design, and storage/back-up concerns are overcome, these technologies appear destined to be a cornerstone of precision medicine and personalized patient care, and to become a routine part of pathology practice.

Intravoxel incoherent motion MRI for monitoring the therapeutic response of hepatocellular carcinoma to sorafenib treatment in mouse xenograft tumor models.

Background With the introduction of targeted therapies, there has been a growing need for non-invasive imaging methods which accurately evaluate therapeutic effects and overcome the limitations of tumor size-based therapeutic response assessments. Purpose To assess diagnostic values of intra-voxel incoherent motion (IVIM) imaging in evaluating therapeutic effects of sorafenib on hepatocellular carcinoma (HCC) using mouse xenograft model. Material and Methods Twenty-four mice bearing Huh-7 were divided into a control group and two treatment groups received sorafenib doses of 5 mg/kg (5 mg-Tx) or 30 mg/kg (30 mg-Tx). IVIM imaging was performed using 10 b-values (0-900 s/mm2). The apparent diffusion coefficient (ADC), diffusion coefficient ( D), and perfusion fraction ( f) were measured for whole tumors and tumor periphery. Changes between baseline and post-treatment parameters ( Δ ADC, Δ D, and Δ f) were calculated, and these parameters were compared with microvessel density (MVD) and area of tumor cell death. Results The post-treatment f and Δ f for tumor periphery were significantly higher in control group, followed by 5 mg-Tx and 30 mg-Tx ( P < 0.001). MVD showed significant positive correlation with post-treatment f ( r = 0.584, P = 0.003) and negative correlation with D ( r = -0.495, P = 0.014) for tumor periphery, while no parameter showed significant correlation with area of tumor cell death. Conclusion The f is significantly correlated with MVD of HCC, and could potentially be used to evaluate the anti-angiogenic effects of sorafenib.

Tumor-associated antigen CAPERα and microvessel density in hepatocellular carcinoma.

PurposeCAPERα, a tumor-associated antigen, was identified from a cDNA clone with autoantibody from a patient with hepatocellular carcinoma (HCC). It has been implicated, by way of alternative splicing of VEGF pre-mRNA, in the regulation of microvessel formation in Ewing's sarcoma. In this study, we looked for possible association of alterations in CAPERα with microvessel density in HCC.MethodsEnzyme-linked immunosorbent assay using recombinant CAPERα as antigen were used to detect antibody against CAPERα. Immunohistochemistry (IHC) on liver sections was performed to analyze expression profiles of CAPERα, VEGF and CD34 in HCC and control tissues and was further used to assess the correlation of expression among CAPERα, VEGF and CD34 in HCC development.ResultsAutoantibody to CAPERα was highest in HCC (22/76, 28.9%), not detected in prostate cancer (0/79) and at 3.4% (3/88) in breast cancer. In immunohistochemical analysis of grades II and III HCC tissues, significantly decreased immunostaining for CAPERα was observed and this correlated directly with decreased immunostaining for VEGF (R=0.534, P=0.0003). Using CD34 immunostaining for detecting newly formed microvessels, strong staining was observed in grades II and III HCC. Normal liver sections, all of which have high expression of CAPERα were totally negative for CD34 immunostaining. A significant inverse correlation was seen between CAPERα and CD34 immunostaining (R=−0.481, P=0.0012).ConclusionsDecreased expression of CAPERα appears to be correlated with appearance of microvessels. It would be of interest to elucidate the cause of altered CAPERα since new formation of microvessels is important in progression of HCC.

Correlation of adrenomedullin with the erythropoietin receptor and microvessel density in hepatocellular carcinoma.

IntroductionUncontrolled angiogenesis plays an essential role in the occurrence, metastasis and malignant progression of hepatocellular carcinoma (HCC). This study aimed to investigate the expression of adrenomedullin (ADM) in human HCC and its correlation with the expression of erythropoietin receptor (EPOR), microvessel density (MVD) and the tumor pathological characteristics.Material and methodsFresh tumor tissues were obtained from 30 HCC patients after hepatectomy. Ten cirrhotic and 10 normal liver tissues were included as controls. Expression of ADM and EPOR was determined by real-time PCR. The MVD was determined by counting the number of microvessels.ResultsThe MVD and the mRNA levels of ADM and EPOR in cancer tissues were significantly higher than those in the non-cancer tissues (p < 0.05). Expression of ADM was significantly correlated with the MVD and EPOR (r = 0.68 and 0.74, p < 0.01). Adrenomedullin and EPOR mRNA levels in HCC tissues were correlated with capsule invasion, pathological differentiation and tumor metastasis (p < 0.05).ConclusionsOur findings suggest that ADM and EPOR may serve as new regulatory factors involved in angiogenesis of HCC and represent novel targets for the treatment of HCC.

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

Assessment of the microvessel density (MVD) may yield important information leading to an effective antiangiogenic treatment for hepatocellular carcinoma (HCC). The intratumoral MVD of 136 HCC patients was retrospectively evaluated using CD34. The correlation between the MVD and clinicopathological findings was assessed. In addition, the prognostic factors influencing the 2-year disease-free survival (DFS) and overall survival (OS) were analyzed. The MVD of each tumor size group (<2, 2-5 and >5 cm) was 196 ± 51, 181 ± 63 and 147 ± 69. The MVD of each histological grade (well-, moderately and poorly differentiated) was 200 ± 56, 184 ± 61 and 114 ± 55. The optimum cut-off values of the MVD for the 2-year DFS and OS were 118.3 and 112.7, respectively. For the 2-year DFS, high tumor marker levels (α-fetoprotein >100 ng/mL and protein induced by vitamin K absence/antagonist-II >100 mAU/mL), poorly differentiated hepatocellular carcinoma (HCC), a high Ki-67 index (>20%), a large tumor size (>5 cm), vascular invasion, high tumor-node-metastasis (TNM) stage (III/IV) and a low MVD were the significant unfavorable prognostic factors. For the OS, a high Ki-67 index, a large tumor size, vascular invasion, high TNM stage and a low MVD were the significant risk factors for death. By the multivariate analysis, a low MVD was identified as an independent predictor of the 2-year DFS as well as the OS. A low MVD can be used to predict an unfavorable prognosis in HCC patients.

Prognostic value of microvessel density in hepatocellular carcinoma patients: a meta-analysis.

The identification of microvessel density (MVD) in patients suffering from different types of cancer has become a hot point as an emerging and promising biomarker. The aim of the present study is to clarify the prognostic relevance of MVD in hepatocellular carcinoma (HCC). Relevant articles were screened in PubMed and EMBASE databases. Patients' clinical characteristics, overall survival (OS), disease/recurrence-free survival (DFS/RFS), and MVD levels were extracted for further analysis. The statistical analysis derived from the Kaplan-Meier survival curves was calculated indirectly with the methods developed by Parmar, Williamson, and Tierney. Multivariate Cox hazard regression analysis was used directly in Stata 11.0. The pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated to evaluate the prognostic role of MVD in HCC. Our online literature search identified 12 articles including a total of 1,138 HCC patients. Meta-analysis of all the included studies considering survival outcomes showed a positive correlation between poor prognosis and higher-MVD levels. The pooled HRs (and 95% CIs) for OS and DFS/RFS were respectively 2.08 [1.77-2.45] and 2.64 [2.12-3.29]. Subgroup analyses considering tumor stage (I-II/III-IV), tumor size (<5 cm/≥ 5 cm), differentiation (well/poor), or cirrhosis status (≥ 20%/<20%) were also conducted, and all the above analyses supported the prognostic role of MVD in HCC. Our meta-analysis showed that the available evidence supports the proposition that MVD has a good predictive role in HCC, especially when the patients have late stage, large size, or poorly differentiated tumors.

TIE2-expressing monocytes as a diagnostic marker for hepatocellular carcinoma correlates with angiogenesis

Angiogenesis is a critical step in the development and progression of hepatocellular carcinoma (HCC). Myeloid lineage cells, such as macrophages and monocytes, have been reported to regulate angiogenesis in mouse tumor models. TIE2, a receptor of angiopoietins, conveys pro-angiogenic signals and identifies a monocyte/macrophage subset with pro-angiogenic activity. Here, we analyzed the occurrence and kinetics of TIE2-expressing monocytes/macrophages (TEMs) in HCC patients. This study enrolled 168 HCV-infected patients including 89 with HCC. We examined the frequency of TEMs, as defined as CD14+CD16+TIE2+ cells, in the peripheral blood and liver. The localization of TEMs in the liver was determined by immunofluorescence staining. Micro-vessel density in the liver was measured by counting CD34+ vascular structures. We found that the frequency of circulating TEMs was significantly higher in HCC than non-HCC patients, while being higher in the liver than in the blood. In patients who underwent local radio-ablation or resection of HCC, the frequency of TEMs dynamically changed in the blood in parallel with HCC recurrence. Most TEMs were identified in the perivascular areas of tumor tissue. A significant positive correlation was observed between micro-vessel density in HCC and frequency of TEMs in the blood or tumors, suggesting that TEMs are involved in HCC angiogenesis. Receiver operating characteristic analyses revealed the superiority of TEM frequency to AFP, PIVKA-II and ANG-2 serum levels as diagnostic marker for HCC. TEMs increase in patients with HCC and their frequency changes with the therapeutic response or recurrence. We thus suggest that TEM frequency can be used as a diagnostic marker for HCC, potentially reflecting angiogenesis in the liver.

P52 Macrophage inflammatory protein-1 α/CC chemokine ligand 3 and tumour-associated macrophages in hepatitis C virus-related hepatocellular carcinoma: relation to tumour progression and angiogenesis

IntroductionHepatitis C virus (HCV) is a major risk factor for development of hepatocellular carcinoma (HCC), however, the mechanism of hepatocarcinogenesis in HCV infection is still undefined. Chemokines, which can induce...

Expression of claudin 10 protein in hepatocellular carcinoma: impact on survival

To investigate the expression of claudin 10 in hepatocellular carcinoma (HCC) and the impact on angiogenesis and the postoperative survival of HCC patients. The expression of claudin 10 protein was analyzed on samples from 99 HCC patients undergoing hepatectomy with immunohistochemistry and 31 fresh specimens with Western blotting. We examined the relationship between claudin 10 expression with clinicopathological factors, microvessel density (MVD), and postoperative survival. Western blotting and immunohistochemical staining showed that claudin 10 protein was highly expressed in HCC, compared with paraneoplastic liver tissue and normal liver tissue (P<0.01). Claudin 10 protein expression levels were significantly higher in HCC specimens with microscopic venous invasion (P<0.01). MVD in HCC increased with enhanced claudin 10 expression (P<0.01). Kaplan-Meier survival analysis revealed that HCC patients with high claudin 10 expression had significantly shorter overall survival (P=0.01). Multivariate analysis showed that claudin 10 expression was an independent prognostic indicator for postoperative overall survival of HCC patients (P<0.01). Claudin 10 protein is highly expressed in HCC tissue and is closely related to angiogenesis. Claudin 10 protein could be a useful marker to predict poor prognosis of HCC patients after hepatectomy.

Correlative study of contrast-enhanced ultrasonography and microvessel density in hepatocellular carcinoma

Objective To study the correlation between quantitative parameters of contrast-enhanced ultrasonography(CEUS)and microvessel density(MVD)in hepatocellular carcinoma(HCC),and to investigate the value of CEUS in noninvasively assessing HCC angiogenesis.Methods The patients with 28 HCCs confirmed by pathology were examined by CEUS.A new type quantification software SW-UCS was used to delineate time-intensity curve(TIC)and to obtain quantitative parameters of HCC and hepatic parenchyma in region of interest.The quantitative parameters were compared with MVD,which was counted by immunohistochemistry method using CD34 antibody,and the correlation between them was studied.Results The TICs of HCC showed typical contrast-enhancement pattern offast-in and fast-outcomparing with normal hepatic parenchyma.There were significant differences between HCC and hepatic parenchyma in slope of rise time(a3),time to initial peak(TTP),peak intensity(PI),increased signal intensity(ISI)and acceleration time(ACT)(P＜0.05).MVD in HCC(49.36±12.57)was higher than that in hepatic parenchyma(32.46±11.78,P=0.000).For HCC,the PI,ISI and area under curve were positively correlated with MVD,while the slope of decrease to half of peak(a2)was negatively correlated with MVD (P＜0.05).Conclusions The quantitative parameters of CEUS in HCC were correlated with MVD,CEUS can evaluate the angiogenesis of HCC in vivo noninvasively. Key words: Ultrasonography; Microbubbles; Carcinoma,hepatocellular; Neovascularization,pathologic

Expression of livin in hepatocellular carcinom and its significance

Objective To explore the expression of livin in hepatocellular carcinoma(HCC).Methods With the method of immunohistochemical staining,specimens from 42 HCC patients and their corresponding para-carcinoma liver tissues and 12 normal liver controls were studied.The relationship between the livin expression and pathological features as well as microvessel density(MVD)was evaluated.Results The expression of 1ivin in the HCC tissues was much higher than that in the corresponding para-carcinoma liver tissues(X2=39.13,P＜0.05)and normal liver tissues(X2=17.89,P＜0.05).Over expression of livin in HCC was related to the invasion of tumor Edmondson grades (X2=4.690,P＜0.05)and tumor metastasis(X2=4.404,P＜0.05).MVD of HCC with positive expression of livin was much higher than that in HCC with negative expression of livin(P＜0.05).Conclusion The up-regulated expression of the livin protein gene in HCC suggests that livin participates in carcinogenesis.Livin may play a crucial role in the angiogenesis,invasion and metastasis of HCC. Key words: Carcinoma,hepatocellular; Livin; Microvessel density; Immunohistochemistry

Contrast-Enhanced Ultrasonography for Assessment of Tumor Vascularity in Hepatocellular Carcinoma

Studies have shown that angiogenesis is a critical factor for tumor growth and metastasis in a variety of human tumors. Although various methods have been tried to assess vessels in tumors, including microvessel density (MVD), assessment of tumor vessels by radiologic techniques is not well established. The aim of this study was to investigate the efficacy of contrast-enhanced ultrasonography (CEUS) in determining the tumor vascularity of hepatocellular carcinoma (HCC). Contrast-enhanced ultrasonography was done in 50 patients with HCC, which was shown histopathologically through subsequent hepatic resection. A contrast pulse sequencing technique and quantitative auto-tracking contrast quantification software were used to analyze the peak intensity (PI) of HCC. Immunohistochemistry was performed to evaluate the level of MVD in HCC. Then the relationship between PI and the level of MVD was analyzed. The mean PIs of HCC and peripheral tissue +/- SD were 135.19 +/- 28.16 and 72.91 +/- 19.22 dB, respectively. The MVDs of HCC and peripheral tissue were 43.44 +/- 12.22 and 17.14 +/- 9.18, respectively. The values of PI and MVD of HCC were significantly higher than those of peripheral tissue. A significant correlation was found between PI and MVD in HCC tissues (P < .05). The PI in CEUS could reflect the MVD in HCC. Therefore, quantification of CEUS seems to be helpful for assessment of tumor vascularity in HCC.

Altered p-STAT3 (tyr705) expression is associated with histological grading and intratumour microvessel density in hepatocellular carcinoma

Background: Constitutive activation of signal transducer and activator of transcription 3 at tyrosine residue 705 (p-STAT3 (tyr705)) has been associated with many types of human cancers. However, its potential roles...

Role of transforming growth factor-beta1-smad signal transduction pathway in patients with hepatocellular carcinoma

To explore the role of transforming growth factor-beta1 (TGF-beta1)-smad signal transduction pathway in patients with hepatocellular carcinoma. Thirty-six hepatocellular carcinoma specimens were obtained from Qidong Liver Cancer Institute and Department of Pathology of the Second Affiliated Hospital of Nanjing Medical University. All primary antibodies (polyclonal antibodies) to TGF-beta1, type II Transforming growth factor-beta receptor (TbetaR-II), nuclear factor-kappaB (NF-kappaB), CD34, smad4 and smad7,secondary antibodies and immunohistochemical kit were purchased from Zhongshan Biotechnology Limited Company (Beijing, China). The expressions of TGF-beta1, TbetaR-II, NF-kappaB, smad4 and smad7 proteins in 36 specimens of hepatocellular carcinoma (HCC) and its adjacent tissue were separately detected by immunohistochemistry to observe the relationship between TGF-beta1 and TbetaR-II, between NF-kappaB and TGF-beta1, between smad4 and smad7 and between TGF-beta1 or TbetaR-IIand microvessel density (MVD). MVD was determined by labelling the vessel endothelial cells with CD34. The expression of TGF-beta1, smad7 and MVD was higher in HCC tissue than in adjacent HCC tissue (P<0.01, P<0.05, P<0.01 respectively). The expression of TbetaR-IIand smad4 was lower in HCC tissue than in its adjacent tissue (P<0.01, P<0.05 respectively). The expression of TGF-beta1 protein and NF-kappaB protein was consistent in HCC tissue. The expression of TGF-beta1 and MVD was also consistent in HCC tissue. The expression of TbetaR-IIwas negatively correlated with that of MVD in HCC tissue. The expressions of TGF-beta1, TbetaR-II, NF-kappaB, smad4 and smad7 in HCC tissue, which are major up and down stream factors of TGF-beta1-smad signal transduction pathway , are abnormal. These factors are closely related with MVD and may play an important role in HCC angiogenesis. The inhibitory action of TGF-beta1 is weakened in hepatic carcinoma cells because of abnormality of TGF-beta1 receptors (such as TbetaR-II) and postreceptors (such as smad4 and smad7). NF-kappaB may cause activation and production of TGF-beta1.

Correlative study of angiogenesis and dynamic contrast‐enhanced magnetic resonance imaging features of hepatocellular carcinoma

To explore the correlation between contrast-enhancement patterns on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and angiogenesis by analyzing microvessel density (MVD), vascular endothelial growth factor (VEGF), and P53 protein expression in hepatocellular carcinoma (HCC). MRI was performed with a GE Signa 1.5T MR scanner using SE and FMPSPGR sequences in 30 patients (38 lesions) during the period October 1998 to March 2000. All had histopathologically proven HCC. MR images were reviewed/ analyzed retrospectively. The 30 patients were between 35 and 65 years of age (average age 58; 18 M and 12 F). SE T1WI, PDWI, and T2WI were acquired initially. The FMPSPGR sequence was acquired in the same position. The DCE-MRI was performed in the arterial, portal vein, and delay phase after a bolus injection of Gd-DTPA. The specimens were stained immunohistochemically for CD34, VEGF, and P53. MVD was highlighted by anti-CD34 antibody staining. The enhancement features of HCC lesions were studied correlatively with the tumor MVD, VEGF, and P53 expression at protein level. In the arterial phase, the results showed that MVD of HCC in the high-enhancement group (229.76 +/- 80.96) was higher than that in the equal-enhancement (173.09 +/- 61.38) and low-enhancement groups (153.00 +/- 108.58) (P < 0.01, respectively). VEGF expression of HCC in the high-enhancement group (68.42%) was higher than that in the equal-enhancement (36.36%) and low-enhancement groups (38.89%) (P < 0.05, respectively). In the portal vein phase, MVD of HCC in the enhancement group (259.80 +/- 93.30) was higher than that in the non-enhancement group (178.64 +/- 92.65) (P < 0.05). No significant correlation was found between VEGF expression and the enhancement feature in the portal vein phase. In the delay phase, MVD of HCC in the ring-enhancement group (269.06 +/- 57.89) was significantly higher than that in the non-ring-enhancement group (144.10 +/- 88.90) (P < 0.01). There was a significant difference in VEGF expression between the ring-enhancement group (76.47%) and the non-ring-enhancement group (42.86%) (P < 0.05). No significant correlation was detected between P53 protein expression and the enhancement feature. Relative enhancement (RE) correlated with MVD, but not with VEGF and P53 protein expression. The contrast-enhancement patterns on DCE-MRI are influenced by tumor angiogenesis, as reflected by elevated VEGF expression, and are therefore valuable indicators for accessing tumor angiogenic activity and tumor neovascularization in vivo in HCC patients.

The correlation between CT perfusion parameters and microvessel density in hepatocellular carcinoma

目的 探讨肝细胞癌(HCC)的CT灌注参数与微血管密度(MVD)之间的相关性. 方法以18例行CT灌注扫描检查并经病理及免疫组织化学染色证实的患者为研究对象.CT灌注扫描计算的血供参数包括:肝动脉灌流量(HAP)、门静脉灌流量(PVP)、肝总灌流量(TLP)、肝动脉灌流指数(HAI)、门静脉灌流指数(PVI).病理组织切片经HE及CD34染色,确定癌细胞分化程度及测定组织MVD.分析CT灌注参数与肿瘤恶性程度及MVD之间的相关性.结果 18例中,高分化HCC 5例,中分化HCC 7例,低分化HCC 6例.MVD分别为高分化组73.6个/mm2,中分化组 166.7个/mm2,低分化组238.2个/mm2.各组灌注参数HAP、PVP、TLP、HAI、PVI分别依次为高分化组0.478 ml·min-1·ml-1、0.441 ml·min-1·ml-1、0.918 ml·min-1·ml-1、0.52、0.48;中分化组1.216 ml·min-1·ml-1、0.587 ml·min-1·ml-1、1.803 ml·min-1·ml-1、0.67、0.33;低分化组1.103 ml·min-1·ml-1、0.473 ml·min-1·ml-1、1.576 ml·min-1·ml-1、0.71、0.29.结果表明,高分化HCC的MVD、PVP、TLP、HAI最低,PVI 最高(P值均<0.01);中分化HCC的PVP、TLP最高 (P<0.01);低分化HCC的MVD、HAI最高,PVI最低(P<0.05).结论 CT灌流指数是反映肿瘤恶性程度及肿瘤血管生成的较好指标。

Relationship between microvessel density and telomerase activity in hepatocellular carcinoma.

To study the relationship between microvessel density (MVD), telomerase activity and biological characteristics in hepatocellular carcinoma (HCC). S-P immunohistochemical method and telomeric repeat amplification protocol (TRAP) were respectively used to analyze the MVD and telomerase activity in 58 HCC and adjacent normal tissues. The MVD in HCC with metastasis, lower differentiation or without intact capsule was significantly higher than that in HCC with intact capsule, higher differentiation, or without metastasis. While MVD had no relationship with tumor size, hepatic virus infection and other clinical factors. Telomerase activity was related to differentiation degree, but not to tumor size or histological grade. MVD in HCC with telomerase activity was higher than that in HCC without telomerase activity. MVD and telomerase activity may serve as diagnostic criteria of HCC in earlier stage. Meanwhile, there may be a cooperative effect between MVD and telomerase on the growth and metastasis of HCC.

Microvessel density of malignant and benign hepatic lesions and MRI evaluation.

To study the difference of microvessel density (MVD) between malignant and benign hepatic lesions and study the relationship between MVD and dynamic enhanced magnetic resonance imaging (MRI) for evaluation of microvessels within malignant and benign hepatic lesions. A total of 265 specimens of hepatocellular carcinoma (HCC), 122 cirrhosis tissues and 22 hepatic benign lesions were enrolled for MVD by immunohistochemistry on tissue microarray, of which 49 underwent MRI examination before surgery, then contrast-to-noise ratios (CNR) and enhancement index (EI) in all the phases were calculated. Pearson correlation was performed for correlation analysis between CNR, EI and MVD. MVD of HCC was 22.7+/-15.8 (mean+/-SD), which was obviously higher than that of cirrhosis tissue (8.3+/-7.6, P<0.01), but was not statistically different from that of benign lesions (31.3+/-22.7, P>0.05). Among HCC, MVD of grades I-II was 29.9+/-18.6, which was much higher than those of grade III (22.2+/-18.2, P<0.01) and grade IV (22.9+/-19.0, P<0.01). MVD of HCC (P=0.018) and of benign lesions (P=0.014) were both correlative with CNR in arterial phase. Neoangiogenesis is an important feature for malignant tumor, and MVD may act as a biological marker in differentiating malignant from benign hepatic lesions. Dynamic enhanced MRI, especially image in arterial phase, may act as an MVD evaluation criterion for malignant and benign hepatic lesions.