Different types of tumor microvessels in stageⅠ-ⅢA squamous cell lung cancer and their clinical significance

BACKGROUND Lung cancer(LC)is the leading cause of morbidity and mortality among malignant neoplasms.Improving the diagnosis and treatment of LC remains an urgent task of modern oncology.Previously,we established that in gastric,breast and cervical cancer,tumor microvessels(MVs)differ in morphology and have different prognostic significance.The connection between different types of tumor MVs and the progression of LC is not well understood.AIM To evaluate the morphological features and clinical significance of tumor MVs in lung squamous cell carcinoma(LUSC).METHODS A single-center retrospective cohort study examined medical records and archival paraffin blocks of 62 and 180 patients with stage I-IIIA LUSC in the training and main cohorts,respectively.All patients underwent radical surgery(R0)at the Orenburg Regional Cancer Clinic from May/20/2009 to December/14/2021.Tumor sections were routinely processed,and routine Mayer's hematoxylin and eosin staining and immunohistochemical staining for cluster of differentiation 34(CD34),podoplanin,Snail and hypoxia-inducible factor-1 alpha were performed.The morphological features of different types of tumor MVs,tumor parenchyma and stroma were studied according to clinicopathological characteristics and LUSC prognosis.Statistical analysis was performed using Statistica 10.0 software.Univariate and multivariate logistic regression analyses were performed to identify potential risk factors for LUSC metastasis to regional lymph nodes(RLNs)and disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with and without metastases in RLNs and those with and without disease recurrence.The effectiveness of the predictive models was assessed by the area under the curve.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.A value of P<0.05 was considered to indicate statistical significance.RESULTS Depending on the morphology,we classified tumor vessels into the following types:normal MVs,dilated capillaries(DCs),atypical DCs,DCs with weak expression of CD34,"contact-type"DCs,structures with partial endothelial linings,capillaries in the tumor solid component and lymphatic vessels in lymphoid and polymorphocellular infiltrates.We also evaluated the presence of loose,fine fibrous connective tissue(LFFCT)and retraction clefts in the tumor stroma,tumor spread into the alveolar air spaces(AASs)and fragmentation of the tumor solid component.According to multivariate analysis,the independent predictors of LUSC metastasis in RLNs were central tumor location(P<0.00001),the presence of retraction clefts(P=0.003),capillaries in the tumor solid component(P=0.023)and fragmentation in the tumor solid component(P=0.009),whereas the independent predictors of LUSC recurrence were tumor grade 3(G3)(P=0.001),stage N2(P=0.016),the presence of LFFCT in the tumor stroma(P<0.00001),fragmentation of the tumor solid component(P=0.0001),and the absence of tumor spread through the AASs(P=0.0083).CONCLUSION The results obtained confirm the correctness of our previously proposed classification of different types of tumor vessels and may contribute to improving the diagnosis and treatment of LUSC.

Microvessel density in patients with gastrointestinal stromal tumors:A systematic review and meta-analysis

BACKGROUND Gastrointestinal stromal tumors(GISTs)are considered the most common mesenchymal tumors of the gastrointestinal tract.Microvessel density(MVD)constitutes a direct method of vascularity quantification and has been associated with survival rates in multiple malignancies.AIM To appraise the effect of MVD on the survival of patients with GIST.METHODS This study adhered to Systematic reviews and Meta-Analyses guidelines and the Cochrane Handbook for Systematic Reviews of Interventions.Electronic scholar databases and grey literature repositories were systematically screened.The Fixed Effects or Random Effects models were used according to the Cochran Q test.RESULTS In total,6 eligible studies were identified.The pooled hazard ratio(HR)for disease free survival(DFS)was 8.52(95%CI:1.69-42.84,P=0.009).The odds ratios of disease-free survival between high and low MVD groups at 12 and 60 mo did not reach statistical significance.Significant superiority of the low MVD group in terms of DFS was documented at 36 and 120 mo(OR:8.46,P<0.0001 and OR:22.71,P=0.0003,respectively)as well as at metastases rate(OR:0.11,P=0.0003).CONCLUSION MVD significantly correlates with the HR of DFS and overall survival rates at 36 and 120 mo.Further prospective studies of higher methodological quality are required.

Endocan-expressing microvessel density as a prognostic factor for survival in human gastric cancer

AIM: To investigate the expression of endocan in tumour vessels and the relationships between endocan and the expression of vascular endothelial growth factor(VEGF) and prognosis in gastric cancer.METHODS: This study included 142 patients with confirmed gastric cancer in a single cancer centre between 2008 and 2009. Clinicopathologic features were determined, and an immunohistochemical analysis of endocan-expressing microvessel density(MVD)(endocan-MVD), VEGF and vascular endothelial growth factor receptor 2(VEGFR2) was performed. Potential relationships between endocan-MVD and clinicopathological variables were assessed using a Student's t-test or an analysis of variance test. Spearman's rank correlation was applied to evaluate the relationship between endocan-MVD and the expression of VEGF/VEGFR2. long-term survival of these patients was analysed using univariate and multivariate analyses.RESULTS: Positive staining of endocan was observed in most of the gastric cancer tissues(108/142) and in fewer of the normal gastric tissues. Endocan-MVD was not associated with gender or histological type(P > 0.05), while endocan-MVD was associated with tumour size,Borrmann type, tumour differentiation, tumour invasion, lymph node metastasis and TNM stage(P < 0.05). According to the Spearman's rank correlation analysis, endocan-MVD had a positive correlation with VEGF(r = 0.167, P = 0.047) and VEGFR2(r = 0.410, P = 0.000). The univariate analysis with a log-rank test indicated that the patients with a high level of endocan-MVD had a significantly poorer overall survival rate than those with a low level of endocan-MVD(17.9% vs 64.0%, P = 0.000). The multivariate analysis showed that a high level of endocan-MVD was a valuable prognostic factor.CONCLUSION: Endocan-MVD significantly correlates with the expression of VEGF and VEGFR2 and is a valuable prognostic factor for survival in human gastric cancer.

Microvessel changes in the gerbil hippocampus after cerebral ischemia and reperfusion by Buyang Huanwu decoction pretreatment

Buyang Huanwu decoction （BYHWD） is a classic recipe for the prevention and treatment of ischemic cerebrovascular disease. Gerbils were pretreated with BYHWD, and then subjected to cerebral ischemia and reperfusion. Microvascular changes were determined with laser Doppler monitoring, tannic acid-ferric chloride mordant, and electron microscopy. Results showed that BYHWD pretreatment could enhance the function of hippocampal microvessels, prevent injury, and increase microvasular density and microvasular area density. Thus, these results suggest that BYHWD pretreatment could prevent microvascular occlusion, enhance the capacity of microvascular reperfusion, increase cerebral blood flow, and inhibit neuronal damage, and may be an effective therapy against brain ischemic injury.

Study on the Changes in Microvessel Density in Hepatocellular Carcinoma Following Transcatheter Arterial Chemoembolization

To study the changes in intratumoral microvessel density (MVD) in hepatocellular carcinoma (HCC) following transcatheter arterial chemoembolization (TACE), MVD in 42 HCC specimens histologically verified was studied by using immunohistochemical method. Of all the specimens, 20 were obtained from the patients treated with surgical resection alone, 22 from those with second stage surgical resection after TACE. The results showed that the MVD in HCC tissues was 53.4±21 9 in the TACE group and 27.6±9.2 in the single operating group, respectively, with the difference being significant between them ( P <0.001). It was suggested that TACE might contribute to angiogenesis of HCC, possibly due to anoxic stress and ischemia reperfusion injury.

Evaluation of hepatocellular carcinoma using contrast-enhanced ultrasonography:correlation with microvessel morphology

BACKGROUND: Contrast-enhanced ultrasonography (CEUS) is an important technique for depiction and assessment of tumor vascularity. This study aimed to explore the relationship between the morphological characteristics of tumor microvessels and enhancement patterns on CEUS in hepatocellular carcinoma (HCC). METHODS: Eighty patients with HCC underwent CEUS using SonoVue before hepatectomy. Contrast-enhanced ultrasonographic enhancement patterns and quantitative parameters were recorded. The tumor tissue sections were immunostained with human CD34 monoclonal antibody. The patients were classified into a point-line type group (n=36) and a loop-strip type group (n=44) according to microvessel morphology. The microvascular density (MVD) in the different types of microvessels was calculated. The relationship between enhancement patterns of HCC lesions and morphological characteristics of tumor microvessels was analyzed. RESULTS:TS: The mean MVD in HCC was 22.4 +/- 3.5 per 0.2 mm(2) in the point-line group, and 19.6 +/- 6.7 per 0.2 mm(2) in the loop-strip group, and there was no significant difference between them (t=0.948, P=0.354). In the portal vein phase, hypoenhancement was significantly more frequent in HCC (chi(2)=4.789, P=0.029) in the loop-strip group (40/44, 90.9%) than in the point-line group (26/36, 72.2%). The time to hypoenhancement in the loop-strip group (mean 64.84 +/- 26.16 seconds) was shorter than that in the point-line group (mean 78.39 +/- 28.72 seconds) (t=2.247, P=0.022). The time to hypoenhancement was correlated with MVD in the loop-strip group (r=-0.648, P=0.001). CONCLUSIONS: The enhancement patterns on CEUS are related to tumor microvascular morphology, and the type of microvascular morphology influences CEUS characterization. CEUS, an important noninvasive imaging technique, is used to evaluate microvascular morphology and angiogenesis, providing valuable information for antiangiogenic therapy in HCC. (Hepatobiliary Pancreat Dis Jut 2010; 9:605-610)

Correlation of RUNX3 expression with microvessel density in colorectal adenocarcinoma tissues and clinical significance

Objective: To study the expression of RUNX3 in colorectal adenocarcinoma tissues and its correlation with microvessel density(MVD),and investigate the clinical pathological prognostic significance of RUNX3 and MVD in patients with colorectal cancer,Methods: The expression value of RUNX3 and MVD in 70 specimens' colorectal adenocarcinoma tissues were detected by immunohistochemistry staining technique,The correlation between their expression and the clinicopathologic features was also investigated,Results: The expression value of RUNX3 and the positive rates of RUNX3 in colorectal adenocarcinoma tissues were 3.25±1.14 and 25.71%(18/70),The expression value of MVD in colorectal adenocarcinoma tissues was 13.14±3.23,Expression of RUNX3 and MVD value were correlated with CEA,serosal invasion,liver metastasis,lymph node metastasis,and TNM stage(P<0.01),The expression value of RUNX3 had negative correlations with that of MVD,Conclusions: The high expression of RUNX3 could inhibit tumor microvascular generation in order to have negative control response on invasion and distant metastasis.

Microvessel density at different levels of normal or injured bile duct in dogs and its surgical implications

BACKGROUND:Ischemic recurrent stricture after surgical repair for iatrogenic bile duct injury(BDI)remains a challenge in clinical practice.The present study was designed to investigate whether ischemia is universal and of varied severity at different levels of the proximal bile duct after BDI. METHODS:A total of 30 beagle dogs were randomly divided into control,BDI,and BDI-repaired groups.The BDI animal model was established based on the classic pattern of laparoscopic cholecystectomy-related BDI.The animals were sacrificed on postoperative day 15,and bile duct tissue was harvested to assess microvessel density(MVD)at selected levels of the normal,post-BDI and BDI-repaired bile duct with the CD34 immunohistochemistry technique. RESULTS:In the control group,MVD at level H(high level) was remarkably higher than that at level L(low level).No significant difference was found between MVDs at levels H and M(middle level),as well as at levels M and L.However, the tendency was noted that the closer the level to the hilus, the greater the MVD at that level.In both the BDI and BDI-repaired groups,MVDs at level H were generally greater than those at level L,despite the unremarkable differences between MVDs at neighboring levels.In these two groups,a similar tendency of MVD distribution to that in the control group was found;the closer the level to the injury site,the lower was the MVD at that level.Moreover,compared with the MDVs at the levels M and L in the control group,MVDs at the corresponding levels in the BDI and BDI-repaired groups were all remarkably reduced(P<0.05).In addition,MVDs at all three levels in the BDI group significantly declined further after BDI repair.CONCLUSIONS:After BDI,universal ischemic damage in the injured proximal bile duct develops close to the injury site, while close to the hilus,ischemia is relatively slight.High hepaticojejunostomy,rather than low biloenterostomy or end-to-end duct anastomosis,should be recommended for BDI repair.Great care should be taken to protect the peribiliary plexus during repair.

Effect of Renin Angiotensin System Blockade on the Islet Microvessel Density of Diabetic Rats and Its Relationship with Islet Function

To investigate the effects of rennin angiotensin system blockade on the microvessel density in islets of diabetic rats and its relationship with islet function, diabetes model was created by feeding of high-caloric laboratory chow plus intraperitoneal injection of a small dose of streptozotocin （30 mg/kg）. After 8 weeks intervention with perindopril （AE, n=10） or valsartan （AR, n=10）, the islet function of the animals was evaluated by intravenous insulin release test （IVIRT）. The pancreases were immunohistochemically stained to analyze the content of insulin and vascular endothelial growth factor （VEGF） in the islets. The microvessel density （MVD） of islets was detected by counting CD34 positive cells. The hypoxia inducible factor （HIF）-1α mRNA expression in the islets was detected by RT-PCR. Compared with normal control group （NC, n=10）, the area under the curve for insulin from 0 to 30 min （AUCI0-30） of diabetes group （DM, n=8） was decreased by 66.3%; the insulin relative concentration （IRC） of βcell was decreased significantly; the relative content of VEGF was increased obviously [（–4.21±0.13） vs （–4.06±0.29）]; MVD in islets was decreased by 71.4%; the relative expression of HIF-1α mRNA was increased by 1.19 times （all P〈0.01）. Compared with DM group, the AUCI0-30 of AE and AR group was increased by 44.6% and 34.9% respectively; IRC was also increased significantly; the relative content of VEGF was decreased by 21.2% and 21.7% respectively; MVD was increased by 62.5% and 75.0% respectively; the relative expression of HIF-1α was decreased by 27.2% and 29.0% respectively （all P〈0.01 or P〈0.05）. There were no significant differences in the said indexes between group AE and AR. It is concluded that the blockade of RAS may ameliorate islets function of diabetic rats by increasing the MVD in islets.

Effects of Ligustrazine on Bone Marrow Microvessel Systemin the Early Period of Acute Radiation Injury in Mice

Sublethally irradiated mice were immediately treated with 250 mg/kg Ligustrazine Phosphiatis intraperitoneally twice a day for seven days, and the bone marrow sections of ulna were observed. On the 5th day, the number of bone marrow microvessels of the Ligustrazine group was much greater than that of the control group. On the 7th day, the amount of the control group decreased to normal, while the ligustrazine group was still increasing, and the microvessel area was enlarged obviously. The percentage of the hematopoietic tissue volume in bone marrow between the two groups had no significant difference in the first 7days. On the 7th day after irradiation, the peripheral neutrophilic granulocytes increased in the Ligustrazine group- The results suggested that early use of Ligustrazine after acute radiation injury might improve the blood supply of bone marrow, and be helpful for recovery of hematopoiesis.

Relationship between peritumoral lymphatic microvessel density and the clinical and pathological characteristics of invasive breast cancer

Objective The aim of the study was to determine the morphological characteristics of lymphatic microvessels and the relationship between lymphatic microvessel density(LMVD) and clinical and pathological characteristics of invasive breast cancer.Methods Tissue specimens and clinical pathological data of 51 cases of female breast cancer were collected in the General Hospital of Shenyang Military Region(Shenyang, China) from January 2007 to October 2011. Another 20 breast fibroadenoma tissue samples were used as controls. All specimens were cut into 4-μm slices, and immunohistochemically stained using streptomycin-resistant avidin peroxidase antibody D2-40. SPSS 17.0 for Windows was used to perform all analyses.Results A total of 38 breast cancer tissue specimens showed varied staining with monoclonal antibody D2-40. The rate of positive staining was in these tissues was 74.5%(38/51), which is significantly higher than that observed in breast fibroadenoma tissues(chi-square = 35.197, P = 0.000). The average LMVD in 38 cases of breast cancer was(26.46 ± 10.06) microvessels/100× magnification field, which was higher than that in the control group(t = 10.74, P = 0.000). Microvessels in peritumoral tissues were abundant, with an average LMVD of(38.42 ± 11.38) microvessels/100× magnification field. Based on layered analysis, the expression level of peritumoral LMVD was correlated with metastasis of lymph nodes, tumor size, and the expression of C-erb B-2(P < 0.05); however, there was no correlation with age or expression of estrogen receptors or progesterone receptors(P > 0.05).Conclusion Lymphatic microvessels detected using D2-40 antibody are mainly present in the peritumoral region of breast cancer tissues, and LMVD showed a correlation with lymph node metastasis and the expression of C-erb B-2. Positive lymphatic vessels, especially in the peritumoral region, may provide a path for lymphatic metastasis in breast cancer. Peritumoral LMVD may be used to estimate the prognosis of patients with breast cancer and may aid in research on treatment methods.

An experimental study of early anastomosis of injured microvessels of maxillofacial region in dogs

This study was designed to evaluate whether the microvascularanastomosis of small arteries and veins in the wound area was possible after gun-shot wound was inflicted to the maxillofacial region of a dog.It was found thatsmall vessels could be connected with subsequent patency of their lumen if theoperation was performed on the 3rd day after the debridment of the gunshotWound,which provides a basis for microvascular anastomosis to repairmaxillofacial defect due to gunshot wound with free vascularized flap grafting.Inaddition the best time to have a defect repaired and the healing features of thewounds after vascular anastomosis are discussed.

STUDY ON THE CLINICAL-PATHOLOGICAL SIGNIFICANCE OF MICROVESSEL DENSITY AND VASCULAR ENDOTHILIAL GROWTHFACTOR EXPRESSION IN PRIMARY LIVER CANCER

Objective: To evaluate the clinical-pathological significance of intratumoral microvessel density (MVD) and Vascular Endothelial Growth Factor (VEGF) expression in primary liver cancer (PLC). Methods: A retrospective study from 63 postoperative patients all with small PLC (diameter ≤5 cm) was done. One group of 29 patients developed recurrence or metastasis within 2 years. The other group of 34 patients had no evidence of recurrence or metastasis within 2 years. Three sections were taken from each patient. One for H.E. staining, the other two for VEGF and Bio-UEA-I immunohistochemical staining respectively. MVD was counted by endothelial cells, which were highlighted by Bio-UEA-I. Results: The MVD of the recurrence (or metastasis) group (49.6±29.7) were significantly greater than the other, group (22.7±28.2) (P<0.01); The VEGF positive rate of the recurrence group was 86.2% (25/29), the rate of the other group was 47.1% (16/34). the difference between the 2 groups was stafistically significant (P<0.01). The stage of the tumor, the positive rate of satellite nodules and the positive rate of the portal vein embolus were all significantly different between the 2 groups. Conclusion: Besides tumor stage, satellite nodule and portal vein embolus, the MVD and VEGF are also of prognostic significance.

Issues of origin,morphology and clinical significance of tumor microvessels in gastric cancer

Gastric cancer(GC)remains a serious oncological problem,ranking third in the structure of mortality from malignant neoplasms.Improving treatment outcomes for this pathology largely depends on understanding the pathogenesis and biological characteristics of GC,including the identification and characterization of diagnostic,prognostic,predictive,and therapeutic biomarkers.It is known that the main cause of death from malignant neoplasms and GC,in particular,is tumor metastasis.Given that angiogenesis is a critical process for tumor growth and metastasis,it is now considered an important marker of disease prognosis and sensitivity to anticancer therapy.In the presented review,modern concepts of the mechanisms of tumor vessel formation and the peculiarities of their morphology are considered;data on numerous factors influencing the formation of tumor microvessels and their role in GC progression are summarized;and various approaches to the classification of tumor vessels,as well as the methods for assessing angiogenesis activity in a tumor,are highlighted.Here,results from studies on the prognostic and predictive significance of tumor microvessels in GC are also discussed,and a new classification of tumor microvessels in GC,based on their morphology and clinical significance,is proposed for consideration.

Changes of 5－hydroxytryptamine and dopamine contents in brain microvessels and the influence on cerebral edema at early stage

The contents of 5-hydroxytryptamine(5-HT)and dopamine(DA) in the brain microvessels(BMVs) at the early stage of rat brain injury were measured by using high performance liquid chromatography with electrochemical detector(HPLC-ECD) and the influence of the

Research on the prognosis of different types of microvessels in bladder transitional cell carcinoma

BACKGROUND At present,there is controversy on the role of microvessel density(MVD)in tumors as a prognostic indicator of bladder transitional cell carcinoma(BTCC).However,the MVD in tumors is simply classified based on the expression of several different vascular markers,which has not been related to analytical research on the prognosis of patients with BTCC.AIM To explore the classification of blood vessels in tumors and studied the relationship between MVD and the prognosis of patients with BTCC.METHODS The tissue mass was detected by tissue microarray and immunohistochemical analysis with monoclonal antibodies against CD31,CD34,CD105,and vascular smooth muscle actin to investigate the MVD in BTCC.The measurement data are expressed as the mean±SD.The difference between the groups was analyzed by the t-test,the counting data were analyzed byχ2 test.The Kaplan-Meier survival curve was estimated by the product-limit method.The log-rank time-series test was employed to compare the tumor-free survival curves.RESULTS The MVD was closely related to the pathological grade,invasive depth,and prognosis of BTCC.Significant differences were found between grade I and grade II,grade II and grade III,superficial and invasive type,and the tumor-free survival group and the recurrence or metastasis group(P<0.01).Multivariate analysis showed that undifferentiated MVD was an independent prognostic factor for patient survival time.An inverse correlation between undifferentiated tumor MVD and differentiated tumor MVD in BTCC was also shown.CONCLUSION The classification of blood vessels in BTCC could act as an important prognostic indicator and may also be of great significance in the treatment of cancer.

Relationship between Vasodilation Effect of Aniso-damine and Endothelial Target for Acetylcholine on Microvessels in Rat

Objective To study the effects of anisodamine on microvessels and its relationship with endothelium target for acetylcholine (ETA). Methods Norepinephrine precontracted mesen-teric vascular beds in rat were used to determine changes of tension of vessels in response to anisodamine after removal of endotlielium, coincubated with L- NAME, nitric oxide synthase (NOS ) inhibitor, in-domethacin,cyclo-oxygenase inhibitor and glibenclamide, ATP-dependent K+ channels (KATP) inhibitor. Results Anisodamine produced a vasodilatian effect on mesenteric vascular beds,which was remarkably inhibited after removal of endothelium (P<0. 01). The vasodilation effect of anisodamine was also significantly inhibited after coincubated with indometliacin (1 μmol/U) ,NG-nitro-L-arginine methyl ester (L-NAME,100 μmol/L) and glibenclamide (1 /μmol/L, P< 0. 01, vs control). Conclusion The vasodilation effect of anisodamine on microvessels was mediated by ETA. This is related to prostacyclin,endothelium derived relaxing factor (EDRF) and KATP besides M, a-receptor on vascular smooth muscle cell(VSMC) and calcium-antagonistic effects.

Microvessel density in differentiated thyroid carcinoma:A systematic review and meta-analysis

BACKGROUND Microvessel density(MVD)has been proposed as a direct quantification method of tumor neovascularization.However,the current literature regarding the role of MVD in differentiated thyroid carcinoma(DTC)remains inconclusive.AIM To appraise the effect of tumoral MVD on the survival of patients with DTC.METHODS This meta-analysis was based on the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions.The electronic databases Medline,Web of Science,and Scopus were systematically screened.A fixedeffects or random-effects model was used,according to the Cochran Q test.The data were then extracted and assessed on the basis of the Reference Citation Analysis(https://www.referencecitationanalysis.com/).RESULTS A total of nine studies were included in the present study.Superiority of low MVD tumors in terms of 10-year disease free survival(OR:0.21,95%CI:0.08–0.53)was recorded.Lowly vascularized thyroid cancers had a lower recurrence rate(OR:13.66,95%CI:3.03–61.48).Moreover,relapsing tumors[weighed mean difference(WMD):11.92,95%CI:6.32–17.52]or malignancies with regional lymph node involvement(WMD:8.53,95%CI:0.04–17.02)presented with higher tumoral MVD values.CONCLUSION MVD significantly correlates with the survival outcomes of thyroid cancer patients.However,considering several study limitations,further prospective studies of higher methodological and quality level are required.

Microvessel density is a prognostic marker of human gastric cancer

AIM: To investigate whether microvessel density (MVD) is related with prognosis in gastric cancer patients, and the expression of cyclooxygenase-2 (COX-2) and vessel endothelial growth factor (VEGF) so as to determine the possible role of COX-2 and VEGF in gastric cancer angiogenesis.METHODS: Forty-seven formalin-fixed paraffin-embedded tissue samples of gastric cancer were evaluated for COX-2, VEGF by immunohitochemical staining. To assess tumor angiogenesis, MVD was determined by immunohitochemical staining of endothelial protein factor Ⅷ-related antigen. The relationship among COX-2 and VEGF expression, MVD, and clinicopathologic parameters was analyzed. RESULTS: Among the 67 samples, high MVD was significantly associated with lymph node metastasis and poor survival. Multivariate survival analysis showed that MVD value and lymph node metastasis were independent prognostic factors. The expression rate of COX-2 and VEGF was significantly higher than that of the adjacent tissues. COX-2 and VEGF expression in gastric cancer was significantly correlated with tumor differentiation and depth of invasion, but not with survival. The mean MVD value of COX-2 or VEGF positive tumors was higher than that of COX-2 or VEGF negative tumors. A significant correlation was found between the expressions of COX-2and VEGF. CONCLUSION: MVD may be one of the important prognostic factors for gastric cancer patients. COX-2 and VEGF may play an important role in tumor progression by stimulating angiogenesis. VEGF might play a main role in the COX-2 angiogenic pathway. The inhibition of angiogenesis or COX-2, VEGF activity may have an important therapeutic benefit in the control of gastric cancer.

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 von 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, co-accounting of LVD and MVD might be a useful prognostic factor in SCRC.