Clinicopathological and prognostic implications of endoglin （CD105） expression in hepatocellular carcinoma and its adjacent non-tumorous liver

AIM: The expression pattern of endoglin (CD105) in hepatocellular carcinoma (HCC) has not been reported so far. We hypothesized that CD105 could differentially highlight a subset of microvessels in HCC, and intratumoral microvessel density (IMVD) by CD105 immunostaining (IMVD-CD105) could provide better prognostic information than IMVD by CD34 immunostaining (IMVD-CD34). METHODS: Paraffin blocks of tumor and adjacent non-tumorous liver tissues from 86 patients who underwent curative resection of HCC were used for this study. Serial sections were stained for CD105 and CD34, respectively, to highlight the microvessels. IMVD was counted according to a standard protocol. RESULTS: In the HCC tissues, CD105 was either negatively or positively stained only in a subset of microvessels. In contrast, CD34 showed positive and more extensive microvessel staining in all cases examined. However, in the adjacent non-tumorous liver sections, CD105 showed a diffuse pattern of microvessel staining in 20 of 86 cases, while CD34 showed negative or only focal staining of the sinusoids around portal area. Correlation with clinicopathological data demonstrated that lower scores of IMVD-CD105 were found in larger sized tumors [mean 41.4/0.74 mm2 (>5 cm tumor) vs 65.9/0.74 mm2 (≤5 cm tumor), P= 0.043] and more aggressive tumors, as indicated by venous infiltration [36.8/0.74 mm2 (present) vs 64.2/0.74 mm2 (absent), P = 0.020], microsatellite nodules [35.1/0.74 mm2 (present) vs 65.9/0.74 mm2 (absent), P= 0.012], and advanced TNM tumor stage [38.8/0.74 mm2 (stage 3 or 4) vs 68.3/0.74 mm2 (stage 1 or 2), P= 0.014]. No prognostic significance was observed when median values were used as cut-off points using either IMVD-CD105 or IMVD-CD34. However, the presence of the diffuse pattern of CD105 expression in the adjacent non-tumorous liver tissues predicted a poorer disease-free survival (median 8.6 vs 21.5 mo, P= 0.026). CONCLUSION: Our data demonstrate that a lower IMVD-CD105 is associated with larger and more aggressive tumors. In this study, IMVD-CD105 did not provide significant prognostic information. However, active angiogenesis as highlighted by diffuse CD105 staining of the microvessels in the adjacent non-tumorous liver tissues is predictive of early recurrence.     

Morphometric study of microvessels in primary CNS tumors and its correlation with tumor types and grade

IntroductionAlterations of microvasculature are integral to CNS neoplasia, and a diagnostic feature of high-grade gliomas. The objectives of this study were two fold: First, to correlate morphometrically measured microvessel density (MVD), microvessel caliber (VC), and percentage of total microvessel area (%TVA) with WHO histologic grade in various types of primary CNS tumors. Second, to evaluate if such a correlation could be further refined by using mathematical derivatives of measured parameters namely coefficient of variation of VC (COofVC), microvessel cross-sectional area (VCSA), and percentage of total VCSA (%TVCSA).Materials and methodsVarious microvessel parameters were assessed in a variety of 30 primary CNS tumors as consecutively encountered in routine surgical pathology practice including gliomas, meningiomas and others by image morphometry using CD34-immunostained sections. We introduced a novel method of effectively determining VC. Results were correlated with tumor type and grade. Appropriate statistical analysis was performed.ResultsMicrovessel characteristics, especially VC (p < 0.0022), VCSA (p < 0.0164), CVofVC (p < 0.0001), %TVCSA (p < 0.0002) and %TVA (p < 0.0003) of tumors were significantly greater than normal tissue. MVD increased in all tumors, excepting meningiomas, and was significantly higher in gliomas (p < 0.0062). MVD showed negative correlation with VC (r = ? 0.808) and VCSA (r = ? 0.848) in the normal brain but was less significant in tumors. Unlike tumors, caliber distribution of microvessels in normal brain was noted to follow a Gaussian pattern. Histological grades of tumors showed positive correlation with MVD (r = 0.547), VC (r = 0.606), CVofVC (r = 0.623), VCSA (r = 0.485), %TVCSA (r = 0.783) and %TVA (r = 0.603). Calculated scores, estimated from multiple regressions of vessel parameters, correlated well with histological grade, with S2 (calculated using all measured as well as mathematically derived microvessel parameters) being better than S1 (calculated using measured parameters: MVD and VC).ConclusionTumor grades positively correlated with all microvessel parameters, with %TVCSA displaying the best. The correlation of %TVA with tumor grade was weaker than %TVCSA mainly due to the impact of MVD. These findings emphasize the value of VC as effectively measured using our novel method and best illustrated by its derivative %TVCSA (an indicator of blood flow), in addition to the well-recognized value of MVD in tumor prognostication. Multiple regressions of microvessel parameters provided the best correlation with grade. Morphometric analysis of microvessels in CNS tumor facilitates a better understanding of the tumor grade, tumor progression and overall prognosis.     

肝细胞癌生物行为学特性与肿瘤微血管特征的关系研究

探讨肝细胞肝癌（HCC）生物行为学特性与肿瘤微血管特征的关系。收集手术切除的HCC标本52例,进行了肿瘤微血管密度（microvessel density,MVD）记数、微血管直径测量、梁索直径测量、肿瘤直径测量、细胞分化程度分级、癌栓、卫星结节观察。对肿瘤生物行为学特性和微血管特征观察指标进行统计分析。（1）HCC肿块大小与肿瘤MVD相关,与肿瘤微血管直径和肿瘤梁索直径呈正相关趋势;（2）有卫星结节、低分化HCC的MVD较高,肿瘤微血管直径较大;（3）有门脉癌栓的HCC的MVD较高。结论（1）HCC的MVD分布不均匀;（2）HCC在不同生长阶段、不同分化程度,其肿瘤微血管特征是不同的,并有一定的规律;（3）HCC临床生物学特性与肿瘤微血管特征之因果关系有待进一步探讨。     

Lymphangiogenic and angiogenic microvessel density in human primary sporadic colorectal carcinoma

AIM： To investigate the distribution pattern of lymphatic vessels and microvessels in sporadic colorectal carcinoma （SCRC） and their relationship to metastasis and prognosis. METHODS： The lymphatic vessel density （LVD） and microvessel density （MVD） in tumor tissue obtained from 132 patients with primary SCRC, including 74 with metastases and 58 without metastases, were evaluated by immunohistochemistry using antibodies directed against D2-40 and yon Willebrand factor （vWF）. RESULTS： （1） The lymphatic vessels and microvessels at central portions of SCRC often had a reticular architecture with numerous tiny and ill-defined lumina, while those at tumor borders had large and open lumina. The LVD and MVD were both obviously higher in colorectal cancer patients with metastases than in those without （P 〈 0.001）. （2） For each one lymphatic vessel increased, there was a 1.45-fold increase in the risk of metastasis in SCRC. The specificity and sensitivity of LVD in predicting metastasis or non-metastasis in SCRC were 71.62% and 56.90%, respectively, and the corresponding LVD was 5. For each one microvessel increased, there was a 1.11-fold increase in the risk of metastasis in SCRC. The specificity and sensitivity of MVD were 66.22% and 51.72%, respectively. （3） Double labeling immunohistochemistry showed D2-40 immunoreactivity to be specific for lymphatic vessels. （4） Univariate analysis indicated that high LVD, high MVD, as well as co-accounting of high LVD and high MVD were associated with patient＇s poor disease-free survival （Puni 〈 0.05）; multivariate analysis indicated that co-accounting of LVD and MVD was an independent prognostic factor of colorectal cancer, CONCLUSION： D2-40 is a new specific antibody for lymphatic endothelial cells. Lymphogenesis and angiogenesis are commonly seen in SCRC, especially at tumor borders. The detection of LVD and MVD at tumor borders may be useful in predicting metastasis and prognosis in patients with SCRC, and, in particular, coa     

Quantitative analysis of angiogenesis using confocal laser scanning microscopy

Angiogenesis is essential for tumor growth and metastasis. Angiogenesis is commonly quantified by measuring microvessel density (MVD) within tumors. In this report, we compared light microscopy with confocal laser scanning microscopy (CLSM) in the qualitative and quantitative analysis of angiogenesis. MVDs were determined manually in a lung tumor xenograft and a normal skeletal muscle using CD31 immunohistochemical staining and light microscopy. Area of three-dimensional representation of microvessels, detected as CD31 immunofluorescence, was measured automatically using computer-assisted CLSM. By manual counting under light microscopy, the relative level of MVD of the lung tumor vs. skeletal muscle was 0.8. However, the corresponding relative level of microvessels was 3.4 as determined by computer-assisted CLSM. Futhermore, the architecture of microvessels was better delineated with CLSM than with light microscopy. We have applied this CLSM method for analyzing the antiangiogenic effect of an anticancer drug, paclitaxel, in the lung tumor xenograft model. We conclude that CLSM is an appropriate method for quantitative and qualitative analysis of microvasculature in normal and tumor tissues. This revised version was published online in June 2006 with corrections to the Cover Date.     

Single-level dynamic spiral CT of hepatocellular carcinoma：Correlation between imaging features and density of tumor microvessels

AIM: To investigate the correlation of enhancement features of hepatocellular carcinoma (HCC) revealed by single-level dynamic spiral CT scanning (DSCT) with tumor microvessel density (MVD), and to determine the validity of DSCT in assessing in vivo tumor angiogenic activity of HCC. METHODS: Twenty six HCC patients were diagnosed histopathologically. DSCT was performed for all patients according to standard scanning protocol. Time-density curves were generated, relevant curve parameters were measured, and gross enhancement morphology was analyzed. Operation was performed to remove HCC lesions 1 to 2 weeks following CT scan. Histopathological slides were carefully prepared for the standard F(8)RA immunohistochemical staining and tumor microvessel counting. Enhancement imaging features of HCC lesions were correlatively studied with tumor MVD and its intra-tumor distribution characteristics. RESULTS: On DSCT images of HCC lesions, three patterns of time-density curve and three types of gross enhancement morphology were recognized. Histomorphologically, the distribution of positively stained tumor endothelial cells within tumor was categorized into 3 types. Curve parameters such as peak enhancement value and contrast enhancement ratio were significantly correlated with tumor tissue MVD (r=0.508 and r=0.423, P<0.01 and P<0.05 respectively). Both the pattern of time-density curve and the gross enhancement morphology of HCC lesions were also correlated with tumor MVD, and reflected the distributive features of tumor microvessels within HCC lesions. Correlation between the likelihood of intrahepatic metastasis of HCC lesions with densely enhanced pseudocapsules and rich pseudocapsular tumor MVD was found. CONCLUSION: Enhancement imaging features of HCC lesions on DSCT scanning are correlated with tumor MVD, and reflect the intra-tumor distribution characteristics of tumor microvessels. DSCT is valuable in assessing the angiogenic activity and tumor neovascularity of HCC patients in vivo.     

Different pathways of macromolecule extravasation from hyperpermeable tumor vessels

Tumor microvessels are hyperpermeable to plasma proteins, a consequence of tumor cell-secreted vascular permeability factor/vascular endothelial growth factor (VPF/VEGF). However, the pathways by which macromolecules extravasate from tumor vessels have been little investigated. To characterize tumor vessels more precisely and to elucidate the pathways by which macromolecules extravasated from them, we studied two well-defined, VPF/VEGF-secreting murine carcinomas, MOT and TA3/St. Whether grown in ascites or solid form, MOT tumors induced large, pericyte-poor "mother" vessels whose lining endothelium developed fenestrae that involved 1.8-5.6% of the surface. Fenestrae developed in parallel with markedly reduced endothelial cell vesiculo-vacuolar organelles (VVOs). TA3/St tumors, which secreted more VPF/VEGF than MOT tumors, elicited mother vessels with unchanged VVOs and without fenestrae. In both tumors, a plasma protein tracer, ferritin, extravasated through VVOs and in MOT tumors ferritin also extravasated through fenestrae. Endothelial gaps were not observed in either tumor. Thus, not all VPF/VEGF-secreting tumors induce fenestrated endothelium. Also, VVOs provide an internal store of membrane that can be transferred to the endothelial cell surface to provide the substantial increase in plasma membrane necessary for mother vessel formation in MOT tumors. Such transfer was apparently unnecessary in TA3/St tumors in which extensive early endothelial cell division provided the increased plasma membrane necessary for forming mother vessels.     

Cyclooxygenase-2 overexpression correlates with vascular endothelial growth factor expression and tumor angiogenesis in gastric cancer

Angiogenesis is a key prerequisite for the successful establishment, growth, and dissemination of tumors. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity and cyclooxygenase-2 (COX-2) promotes angiogenesis by modulated production of angiogenic factors including VEGF. The current study was designed to investigate the possible roles of COX-2 and VEGF in gastric cancer angiogenesis. In this study, we conducted an immunohistochemical investigation of COX-2 and VEGF expression in 97 patients with gastric cancer. To assess tumor angiogenesis, microvessel density (MVD) was determined by CD34 immunohistochemical staining. Expression of COX-2 and VEGF in gastric cancer tissues, was demonstrated in 63.9% and 75.3% of cases, respectively. The expression of COX-2 correlated significantly with VEGF expression. High MVD was significantly associated with depth of tumor invasion and poor survival. The mean MVD value of VEGF positive tumors was 79.8 +/- 32.0 and significantly higher than that of VEGF negative tumors. The mean MVD value of COX-2 positive tumors was 77.9 +/- 29.9 and not significantly higher than that of COX-2 negative tumor. The mean value of MVD in tumors positive for both COX-2 and VEGF was significantly higher than that in tumors negative for both. However, there was no correlation between COX-2 or VEGF expression and various clinicopathological features including patient survival. These results suggest that COX-2 may play an important role in carcinogenesis by stimulating tumor angiogenesis in concert with VEGF in human gastric cancer.     

Evaluation of serum vascular endothelial growth factor (VEGF) and microvessel density (MVD) as prognostic indicators in carcinoma breast

Purpose  Vascular endothelial growth factor (VEGF) is a potent angiogenic peptide. A great deal of interest has been paid to the predictive value of neoangiogenesis represented by microvessel density (MVD), on clinical progression and prognosis of several types of tumors. Serum VEGF levels may therefore be clinically useful for the prediction of increase in tumor growth, metastasis or recurrence spread in individual patients. Methods  A total of 265 cases of breast lesions were studied to note the importance of Serum VEGF as a prognostic marker in cases of breast carcinoma. The expressed serum VEGF levels and microvessel density (MVD) were assessed quantitatively and were correlated with tumor grade, tumor necrosis, stromal reaction and nodal metastasis. Results  Serum VEGF was increased in patients with lesions of breast and the levels of serum VEGF in malignant lesions were significantly increased when compared to benign lesions. It was also noted that the levels of serum VEGF increased with increasing grades of malignancy. MVD showed a significant correlation in the early stages of the malignant tumors, where there was no necrosis, but in tumors associated with necrosis and hemorrhage MVD failed to show significant correlation. Conclusion  Hence, serum vascular endothelial growth factor can be used as a more reliable, non-invasive adjunctive diagnostic criteria in the assessment of the grade and hence, the prognosis of malignant tumors of the breast. S. Shivakumar and B. T. Prabhakar have contributed equally to this work.     

Podoplanin expression in advanced-stage gastric carcinoma and prognostic value of lymphatic microvessel density

In gastric cancer, lymph node metastasis is a major prognostic factor. Tumor lymphangiogenesis promotes metastasis in experimental models, but in human tumors data about the presence and clinical significance of lymphatic vessels in the tumor area are controversial. We investigated 70 patients with advanced-stage gastric carcinoma and the pathological examination showed 40 cases with intestinal subtype and 30 cases with diffuse subtype. Forty three from 70 cases had regional lymph node metastasis. Additional slides were stained with an antibody against podoplanin, and lymphatic microvessel density (LMVD) was evaluated in the tumoral and peritumoral areas. Lymphatic vessels were identified in tumor area in all cases and LMVD was higher in the peritumoral than in the tumor area. Podoplanin-positive vessels in tumor area were usually small, with narrow lumen. A significant correlation was found between LMVD and stage of the tumor (p<0.002) and lymph node metastasis (p<0.031), but not with the pathological subtype and grade of the tumor. We found tumor cells in the lumen of lymphatic vessels in 11 cases, whereas tumor cells expressing podoplanin were found in 4 cases of less differentiated diffuse subtype gastric carcinoma. In conclusion, our results suggest that LMVD predicts tumor stage and lymph node metastasis, and podoplanin-positive tumor cells select a subgroup of tumors with high potential of invasion and metastasis. Key words: gastric cancer, podoplanin, lymphatic microvessel density (LMVD), lymphangiogenesis, prognosis.     

星形细胞肿瘤组织中VEGF—A、VEGF—C的表达变化及其与肿瘤血管生成的关系

目的观察血管内皮生长因子（VEGF）．A和VEGF—C在星形细胞肿瘤组织中的表达变化,分析两指标间及与肿瘤血管生成的关系。方法留取93例星形细胞肿瘤患者肿瘤组织及9例接受高血压脑出血开颅手术患者的正常脑组织,用免疫组织化学（sP）方法检测VEGF-A、VEGF-C蛋白表达和微血管密度（MVD）,RT-PCR法检测VEGF．A、VEGF．CmRNA表达,对两VEGF间及与肿瘤WHO分级、MVD的关系进行统计学分析。结果星形细胞肿瘤组织中VEGF．A、VEGF．C蛋白阳性表达率及MVD均显著高于正常脑组织,且均随肿瘤恶性程度增高而增强（P均〈0．叭）;星形细胞肿瘤组织中VEGF—A、VEGF-C蛋白表达及两者与MVD均呈显著相关（P均〈0．01）。星形细胞肿瘤组织中VEGF—A和VEGF．CmRNA表达均显著高于正常脑组织,且均随肿瘤恶性程度增高而增强（P均〈0．05）;肿瘤组织中VEGF．A和VEGF．CmRNA表达呈显著相关（P均〈0．05）。结论VEGF—A、VEGF—C在星形细胞肿瘤组织中的表达上调并与肿瘤恶性程度有关,两者间及与肿瘤血管生成均关系密切。     

Chronic administration of a gonadotropin-releasing hormone (GnRH) agonist affects testicular microvasculature

Three months of daily sc injections of adult male dogs with the gonadotropin-releasing hormone agonist (GnRH-A) [D-Trp6, des-Gly-NH2(10)]GnRH ethylamide produced significant decrease in the diameter of seminiferous tubules and conspicuously altered the ultrastructure of testicular microvasculature. In contrast to capillaries and venules in untreated controls, which had typical continuous endothelial layers surrounded by a basal lamina, in testes of dogs chronically treated with GnRH-A, 14.3% of the capillaries and 21.2% of the venules showed wide (30-500 nm) endothelial gaps. In a few capillaries (1.7%) and venules (4%) endothelial fenestrations were found. A high percentage of capillaries (59.3%) and venules (32.8%), with endothelial gaps or continuous endothelium were surrounded by multiple layers of basal lamina. All arterioles, 24.7% of the capillaries and 42.6% of the venules showed the normal features as found in the controls. Superfluous basal laminae, not associated with cells were present in the testes of the chronically treated dogs, but were also found after 4 months of recovery from the GnRH-A treatment. However, within 4 months after cessation of the GnRH-A treatment, the diameters of the seminiferous tubules were comparable to those in untreated controls. Capillaries and venules with endothelial gaps or fenestrations were completely absent. All arterioles, 43.6% of the capillaries and 65.6% of the venules revealed the normal features of continuous endothelium. However, 56.4% of the capillaries and 34.4% of the venules were characterized by superfluous layers of basal lamina.(ABSTRACT TRUNCATED AT 250 WORDS)     

血管内皮细胞生长因子的表达及微血管密度与胆囊癌浸润、转移及预后的相关研究

探讨血管内皮细胞生长因子 (vascularendothelialgrowthfactor,VEGF)及微血管密度 (Microvesseldensity ,MVD)在胆囊癌发生发展中的作用及与胆囊癌浸润、转移及预后的关系。应用S -P免疫组化技术对 3 1例经手术切除的原发性胆囊癌及 10例经手术切除的慢性胆囊炎标本进行VEGF蛋白和微血管密度检测。 3 1例胆囊癌组织中癌旁VEGF表达及MVD值均明显高于癌中央及正常组织 ,三者差异具有显著性 (P <0 0 1) ;VEGF表达与MVD具有相关性 ,VEGF阳性者MVD值显著高于阴性者 (P <0 0 1) ;VEGF表达和MVD与胆囊癌分化程度、浸润转移、Nevin分期密切相关 (P <0 0 1) ;VEGF阳性者及高MVD者预后较阴性者差 ;Cox比例危险模型多因素分析表明 :VEGF对胆囊癌是一个独立的预后因子。VEGF的表达及MVD在胆囊癌的发生和浸润转移过程中发挥重要的作用 ,VEGF和MVD可作为反映胆囊癌生物学行为的指标     

Synergistic anti-tumor effect of recombinant chicken fibroblast growth factor receptor-1-mediated anti-angiogenesis and low-dose gemcitabine in a mouse colon adenocarcinoma model

AIM: To evaluate whether the combination of recom- binant chicken fibroblast growth factor receptor -1 (FGFR-1) protein vaccine (cFR-1) combined with low- dose gemcitabine would improve anti-tumor efficacy in a mouse CT26 colon adenocarcinoma (CT26) model. METHODS: The CT26 model was established in BABL/c mice. Seven days after tumor cell injection, mice were randomly divided into four groups: combination therapy, cFR-1 alone, gemcitabine alone, and normal saline groups. Tumor growth, survival rate of tumor-bearing mice, and systemic toxicity were observed. The presence of anti-tumor auto-antibodies was detected by Western blot analysis and enzyme-linked immunospot assay, microvessel density (MVD) of the tumors and tumor cell proliferation were detected by Immunohistochemistry staining, and tumor cell apoptosis was detected by TdT- mediated biotinylated-dUTP nick end label staining. RESULTS: The combination therapy results in apparent decreases in tumor volume, microvessel density andtumor cell proliferation, and an increase in apoptosis without obvious side-effects as compared with either therapy alone or normal control groups. Also, both auto- antibodies and the antibody-producing B cells against mouse FGFR-1 were detected in mice immunized with cFR-1 vaccine alone or with combination therapy, but not in non-immunized mice. In addition, the deposition of auto-antibodies on endothelial cells from mice immunized with cFR-1 was observed by immunofluorescent stain- ing, but not on endothelial cells from control groups. Synergistic indexes of tumor volume, MVD, cell apoptosis and proliferation in the combination therapy group were 1.71 vs 1.15 vs 1.11 and 1.04, respectively, 31 d after tumor cell injection. CONCLUSION: The combination of cFR-1-mediated anti- angiogenesis and low-dose gemcitabine synergistically enhances the anti-tumor activity without overt toxicity in mice.     

胃癌组织碱性成纤维细胞生长因子表达及对血管新生和肿瘤进展的影响

目的　探讨碱性成纤维细胞生长因子 (bFGF)在胃癌组织中表达及其对血管新生和肿瘤生物学行为的影响。方法　应用免疫组化SP法检测 74例胃癌 ,17例癌旁组织bFGF表达及间质微血管密度 (MVD)。结果　胃癌组织中肿瘤细胞、间质新生血管高度表达bFGF。癌组织bFGF表达(77.0 3% )明显高于癌旁组织 (2 9.4 1% ,P <0 .0 1)。癌旁胃黏膜及伴有肠上皮化生的胃黏膜表达bFGF较弱。bFGF高表达组的平均MVD值 (79.3± 11.2 )明显高于bFGF低表达组 (71.2± 11.9,P <0 .0 5 )。此外bFGF表达程度与胃癌淋巴结转移和癌浸润深度密切相关。结论　bFGF可促进肿瘤间质微血管生成 ,加速肿瘤浸润和转移。     

Expression of PTEN and its correlation with angiogenesis in gastric carcinoma]

BACKGROUND/AIMS: Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a recently clarified tumor suppressor gene located in 10q23.3. Alterations of this gene are associated with tumor progression and unfavorable outcome in various human cancers. Recently, PTEN has a possible role in angiogenesis by modulating angiogenic factor including vascular endothelial growth factor (VEGF). The aim of this study was to investigate the roles of PTEN and VEGF status for angiogenesis in human gastric cancer. METHODS: We conducted an immunohistochemical investigation of PTEN and VEGF expression in 90 cases of paraffin section obtained from gastric cancer patients undergone surgical treatment. RESULTS: Negative expression of PTEN and positive expression of VEGF in gastric cancer tissues, were demonstrated in 40.0% and 77.8% of cases, respectively. However, no significant correlation was found between PTEN, VEGF expression and various clinicopathological parameters. PTEN expression did not correlate significantly with VEGF expression (p=0.301). High microvessel density (MVD) was significantly associated with lymph node metastasis and poor survival (p=0.014, 0.011, respectively). The mean MVD value of PTEN negative tumors was 90.4+/-43.0 and significantly higher than that of PTEN positive tumors (p=0.028). The mean MVD value of VEGF positive tumors was 86.4+/-6.7 and significantly higher than that of VEGF negative tumors (p=0.002). The mean MVD value of PTEN negative and VEGF positive tumors was 98.0+/-42.2, and significantly higher than those of the others. CONCLUSIONS: These results suggest that loss of PTEN expression may play a critical role in tumor progression and metastasis by stimulating tumor angiogenesis in human gastric cancer.     

Comparison of microvessel density before and after peripheral blood stem cell transplantation in multiple myeloma patients and its clinical implications: multicenter trial

Bone marrow angiogenesis has been reported to increase in several hematologic malignant diseases, including multiple myeloma. Because high-dose chemotherapy combined with autologous stem cell transplantation (SCT) improves the response rate, event-free survival, and overall survival in patients with multiple myeloma (MM), we studied the changes in bone marrow microvessel density (MVD) in 21 patients who underwent high-dose chemotherapy combined with autologous SCT to determine whether there was persistently increased angiogenesis at the time of response. Bone marrow biopsy specimens were obtained before and after SCT for each patient and immunostained with anti-CD34 antibodies for the identification of microvascular endothelial cells. The mean value of MVD in 21 MM patients at initial diagnosis was 46.0 +/- 24.0 and in healthy controls was 26.8 +/- 8.54 (P = .046). The mean MVD at initial diagnosis was 46.0 +/- 24.0 compared with 29.0 +/- 12.5 after achievement of response with SCT, and there was a statistically significant difference (P = .004). Sixteen of 21 patients (76.2%) had decreased MVD after SCT, and 5 patients were found to have a greater than 50% decrease in MVD after SCT. However, there was no difference in overall survival between the patient group with decreased MVD after SCT and that without decreased MVD (P = .9370). These results suggest that angiogenesis plays an important role in MM. In addition, the persistence of MVD at the time of response indicates continuous stimulus of microvessels by minimal residual disease even after SCT.     

Microvessel density is a prognostic marker of human gastric cancer

INTRODUCTIONGastric cancer is one of the most frequent and lethal malignancies worldwide, especially in Eastern Asia including China, and the 5-year survival rate is only about 20%[1]. A recent research has shown an increasing trend of gastric cancer mortality in China in the past 20 years, especially in rural areas and among aged people[2]. To date, the treatment outcome of this common malignancy is still not satisfactory. One major difficulty in the diagnosis and treatment of gastric c…     

Expression of survivin in gastric cancer and its relationship with tumor angiogenesis

BACKGROUND/AIMS: Survivin, a member of inhibitors of apoptosis, has been found in various human cancers. Its expression is associated with tumor progression and adverse outcome. Angiogenesis is an essential process for the primary tumor to grow and invade the adjacent normal structures. Angiogenic factors such as vascular endothelial growth factor induce survivin expression in endothelial cells. The current study was designed to investigate the possible role of survivin and vascular endothelial growth factor status for angiogenesis in human gastric cancer. METHODS: In this study, we conducted an immunohistochemical investigation of survivin and vascular endothelial growth factor expression in 106 tissue samples obtained from gastric cancer patients undergoing surgical treatment. To assess tumor angiogenesis, microvessel density was counted by staining endothelial cells immunohistochemically using anti-CD34 monoclonal antibody. RESULTS: The positive expression of survivin and vascular endothelial growth factor in gastric cancer tissues was demonstrated in 50.0 and 69.8% of cases, respectively. The expression of survivin did not associate with vascular endothelial growth factor expression. Expression of survivin was significantly associated with tumor size, depth of invasion, lymph node metastasis, tumor stage and poor survival (P=0.011, 0.004, 0.020, 0.002, 0.046, respectively). High microvessel density was significantly associated with lymph node metastasis and poor survival (P=0.006 and 0.017, respectively). The mean microvessel density value of survivin positive tumors was 87.4+/-34.4 and significantly higher than that of survivin negative tumors (P=0.016). The mean microvessel density value of vascular endothelial growth factor positive tumors was 98.7+/-37.0 and significantly higher than that of vascular endothelial growth factor negative tumors (P=0.001). A combined analysis of survivin and vascular endothelial growth factor status showed that the mean microvessel density value of both positive tumors was 103.7+/-33.1 and significantly higher than that of both negative tumors (P<0.001). CONCLUSION: These results suggest that survivin may play an important role in carcinogenesis by stimulating tumor angiogenesis in human gastric cancer.     

瘤内微血管密度与舌癌术后复发的相关性研究

应用免疫组化方法（ＬＡＳＢ法）对３８例舌癌患者进行了血管内皮细胞染色观察。结果发现，复发组舌癌中的瘤内微血管密度（ＩＭＶＤ）较未复发组明显升高、差异有显著性（Ｐ〈０．００１），两组间的肿瘤分化程度、临床分期、肿瘤大小无显著性差异（Ｐ〉０．０５）。提示肿瘤复发与ＩＭＶＤ有关，ＩＭＶＤ可作为预测舌瘤复发的指标。