Density of intranodal lymphatics and VEGF-C expression in B-cell lymphoma and reactive lymph nodes

Lymphatic vasculature in solid tumors may serve as the pathway for metastatic spread of the cancer to the regional lymph nodes and to distant organs. Controversy still exists whether tumors metastasize through existing lymphatics or through newly formed vessels (lymphangiogenesis). The role of lymphangiogenesis in lymphoma spread and proliferation is not clearly established. VEGF-C is the most potent inducer of lymphangiogenesis. LYVE-1 was shown to be a specific marker for lymphatic vessels in normal and tumor tissue. The aim of the present study was the evaluation of lymph node LYVE-1-positive lymphatic sinus density (LSD) and VEGF-C expression in patients with non-Hodgkin's lymphoma (nHL) and in reactive lymph nodes. Sixty paraffin-embedded lymph nodes from newly diagnosed patients with B-cell nHL were evaluated. Twelve lymph node biopsy specimens from adult patients with reactive lymphonodulitis were used as controls. Sections of lymph nodes were stained immunohistochemically for LYVE-1 and VEGF-C. VEGF-C expression in lymph nodes of nHL patients was low and not significantly different from that in the control (p = 0.6). Moreover, VEGF-C expression did not differ significantly between aggressive and indolent lymphomas (p = 0.53). Similarly we did not find differences in LSD in aggressive nHL and in indolent nHL (p=0.49). The mean LSD in reactive lymph nodes was higher than in nHL (p = 0.03). Only in 2 out of 12 reactive lymph nodes LYVE-1-positive vessels were absent. In all groups we demonstrated a strong positive correlation between VEGF-C and LYVE-1-expression (p = 0.0001). Higher LSD in reactive lymph nodes as compared to those of nHL patients suggests that lymphoma proliferation leads to the destruction of the existing lymphatics rather than to lymphangiogenesis within lymph nodes. NHL are not associated with increased expression of VEGF-C nor increased LYVE-1-positive lymphatic sinuses density within lymph nodes.     

Angiogenesis in gliomas

Brain gliomas are characterized by invasive growth and neovascularisation potential. Angiogenesis plays a major role in the progression of gliomas and its determination has a great prognostic value. The aim of the study was to assess the vascularisation of chosen brain gliomas and to estimate how it is correlated with tumour histological type, malignancy grade, location and size, and with age and sex of patients. Tumour vascularisation analysis was based on the determination of microvascular proliferation (MVP) and microvessel density (MVD). Microvascular proliferation was measured with immunohistochemical methods using mouse monoclonal antibodies to detect cell proliferation antigens. The following antibodies were used Ki-67 and PCNA (DAKO). Identification of vessels was performed by CD31 antibody and anti-human von Willebrand factor (DAKO). The highest microvascular proliferation and microvascular density were observed in multiform glioblastomas and the lowest in oligodendrogliomas. Significant correlation was observed between the vascularisation and malignancy grade.     

Morphological parameters of the angiogenic response in pancreatic ductal adenocarcinoma--correlation with histological grading and clinical data.

The aim of this study was to evaluate angiogenesis in tissue of the pancreatic ductal adenocarcinoma and to correlate it with histopathological data such as tumour differentiation, tumour size, lymph node metastasis and patients survival. Tumour samples obtained during surgery from 36 patients were immunostained for the presence of blood vessels with monoclonal antibody against the CD31 molecule. Evaluation of microvasculature was perfomed by counting the microvessel density (MVD) in selected areas under light microscope as well as by computer assisted image analysis (CAIA). In the latter, the following parameters were used for assessment of microvessels: mean number/field, mean area of the vessels, total area/field and total perimeter/field. MVD values obtained under optical microscope and with CAIA were highly correlated. All parameters characterising microvasculature in CAIA also revealed a significant correlation with the histological grading of tumours; generally the less differentiated tumours manifested more extensive vascular network. No significant relationship was found between the tumour size and any of the CAIA parameters. The area of vessels (both total and mean values) revealed a significant, inverse correlation with the incidence of lymph node metastases. The same type of correlation was also found between the mean vessel area and the postoperative survival period. The results show that CAIA of microvessels offers new parameters with some predictive value for the outcome of patients with pancreatic cancer.     

食管鳞癌VEGF—C mRNA和CD31表达及其意义

To investigate the expression of vascular endothelial growth factor-C (VEGF-C) mRNA and CD 31 in esophageal squamous cell carcinoma (ESCC) and its promotion of lymphatic metastasis. The expression of VEGF-C mRNA was examined in 43 ESCC by in situ hybridization. Intratumoral microvessel density (MVD) was assessed by immunostaining endothelial cells, using anti-CD31 antibody. The positive rate of VEGF-C mRNA expression was 41.86%. The average rank of MVD was 76.36 +/- 20.30/mm2. VEGF-C mRNA expression correlated significantly with lymph node metastasis, TNM stage and depth of invasion (p < 0.05 or p < 0.01) in statistic, but not with histological grade (differentiation) (p > 0.05). MVD correlated significantly with lymph node metastasis and TNM stage (p < 0.05) in statistic, but not with depth of invasion and histological grade (differentiation) (p > 0.05). MVD was significant higher in the VEGF-C positive tumors than negative tumors (p < 0.05). The present study indicated that VEGF-C might play a role in lympatic metastasis via lymphangiogenesis and angiogenesis in ESCC.     

Comparative study of tumor angiogenesis and immunohistochemistry for p53, c-ErbB2, c-myc and EGFr as prognostic factors in gastric cancer

Gastric cancer (GC) continues to be a highly aggressive malignancy with poor prognosis and low survival rates. The survival of patients with GC depends mainly on the stage of the disease, with early GC having a 5 year survival of 90-100% and advanced tumors a 5 year survival of 15-25%. The role of other prognostic factors in these tumors is still under investigation. 28 gastric dysplasia, 45 Early GC and 98 Advanced Gastric Cancers were evaluated for expression of the oncogenes p53, c-ErbB2, c-myc and the EGFr in paraffin-embedded material utilizing Avidin-Biotin immunohistochemistry techniques. In 34 cases of GC microvessel density (MVD) was determined in CD34 stained sections. Statistical correlations with stage, histologic type, differentiation degree, location, size, ploidy patterns and overall survival were done. The Mantel-Cox test was performed to evaluate which factors had an independent prognostic value. Both, tumor angiogenesis and p53 protein expression were statistically associated (95% confidence intervals) with overall survival in patients with GC. p53 protein expression was also correlated with cardial location, nodal involvement and tumor stage. c-ErbB2 may recognize a group of highly aggressive well differentiated adenocarcinomas with worse prognosis. c-myc was also significantly enhanced in well differentiated tumors. EGFr showed no significant associations. Mantel-Cox was performed to compare the prognostic value of tumor stage, p53 protein expression and tumor angiogenesis. Tumor angiogenesis was the most important prognostic indicator to predict overall survival in our series. p53 expression was not independent and did not provide additional prognostic information to tumor stage. Our study suggests that angiogenesis as demonstrated by microvessel counts in CD34 stained sections is a significantly important prognostic factor for predicting survival in gastric cancer.     

胃癌中CD44v6 表达及与微血管密度和生物学行为的关系

目的:探讨CD44v6在胃癌中的表达及其与微血管密度(microvessel density,MVD)和生物学行为的关系。方法:采用免疫组化法检测80例胃癌组织CD44v6、CD34的表达,以CD34标记肿瘤微血管,并在显微镜下计数微血管密度(MVD)。结果:CD44v6在胃癌组织中的表达与肿瘤浸润深度、临床分期、淋巴结转移相关(P<0.05),CD44v6强阳性表达组中MVD明显高于CD44v6阴性表达组(P<0.05)。结论:CD44v6的表达和MVD计数是反映胃癌生物学特性的良好的指标,对判断胃癌的浸润转移具有一定的临床意义。     

Evaluation of Angiogenesis in Non-small Cell Lung Carcinoma by CD34 Immunohistochemistry

The objective of the study was to investigate angiogenesis in non-small lung cancer by measuring the expression of CD34. Immunohistochemistry was used to detect CD34 at the endothelial cell surface in 81 surgically resected non-small cell lung cancer specimens. CD34 immunohistochemistry had high specificity and sensitivity with minimal background, which enabled efficient identification of CD34-positive staining. Statistical analysis showed that increased microvessel density (MVD) was closely correlated to tumor progression as reflected by the clinical stage (P < 0.05). However, MVD was not significantly associated with lymph node metastasis and other clinical and pathological features (P > 0.05). In conclusion, microvascular density may play an important role in the development and progression of lung cancer.     

人胰腺癌组织中PFKFB3表达及其与MVD相关性的研究

目的:检测人胰腺癌组织6磷酸果糖激酶2/果糖双磷酸酶2同工酶3(PFKFB3)的表达及微血管密度(MVD),并探讨二者临床意义和相关性。方法:采用免疫组化SP法检测41例胰腺癌组织和11例癌旁组织石蜡块中PFKFB3的表达情况,并对CD34标记阳性的血管进行微血管密度计数,分析PFKFB3、MVD与胰腺癌临床病理特征的相关性及二者之间的相关性。结果:胰腺癌组织和癌旁组织中PFKFB3的阳性表达率分别为63.41%和9.09%,胰腺癌组织显著高于癌旁组织(P0.01);PFKFB3呈阳性和阴性表达的胰腺癌组织MVD值分别为(49.12±12.04)、(35.40±8.12),两者比较差异有统计学意义(P0.01)。PFKFB3表达与胰腺癌的分化程度显著相关(P=0.035),MVD与胰腺癌TNM分期及淋巴结转移显著相关(P0.05)。Spearman等级相关分析显示:胰腺癌PFKFB3表达与MVD值呈显著正相关(r=0.551,P0.01)。结论:胰腺癌组织中PFKFB3呈高表达,可能通过促进血管生成,在胰腺癌的发生发展、转移过程中发挥重要作用,并可能作为胰腺癌预防、治疗和预后评估的参考指标。     

High Expression of HuR in Cytoplasm,but Not Nuclei,Is Associated with Malignant Aggressiveness and Prognosis in Bladder Cancer

Introduction

Human antigen R (HuR) regulates the stability of mRNA and is associated with cell proliferation, angiogenesis, and lymphangiogenesis. However, the clinical significance and pathological role of HuR in bladder cancer remains unclear. The main objective of this investigation was to clarify the relationships between HuR expression and clinical significance and cancer cell proliferation, angiogenesis, lymphangiogenesis, and expressions of cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF)-A, -C, and -D.

Methods

All expressions were examined by immunohistochemical techniques in 122 formalin-fixed specimens of bladder cancer patients. HuR expression was evaluated separately with cytoplasmic and nuclear staining. Cell proliferation, angiogenesis and lymphangiogenesis were measured as the percentage of Ki-67-positive cell (proliferation index, PI), CD34-stained vessels (microvessel density, MVD), and D2-40-stained vessels (lymph vessel density, LVD). Relationships between each HuR expression and clinicopathological features, prognosis, and expressions of COX-2 and VEGFs were analyzed by multi-variate analyses. HuR expression was also investigated in 10 mice of N-Butyl-N-[4-hydroxybutil] nitrosamine (BBN) induced bladder cancer model.

Results

In human tissues, high cytoplasmic expression was seen in 5% and 25.4% of normal and cancer cells, respectively. Nuclear HuR expression bore no significant relationship to any pathological features. However, cytoplasmic HuR expression appeared positively associated with pT stage and grade (P<0.001). In mouse tissues, similar trends were confirmed. Cytoplasmic expression correlated with PI, MVD, and LVD, as well as expression of VEGF-A and -C, but not VEGF-D. High cytoplasmic expression of HuR was a significant predictor of metastasis and cause-specific survival, and was identified as a prognostic correlative factor for metastasis (hazard ratio, 4.75; P = 0.028) in a multivariate analysis model that included pathological features.

Conclusions

Cytoplasmic HuR appears to play important roles in cell proliferation, progression, and survival of bladder cancer patients. Its expression was associated with angiogenesis, lymphangiogenesis, and expressions of VEGF-A and –C.     

Expression and Biological Significance of Leptin,Leptin Receptor,VEGF, and CD34 in Colorectal Carcinoma

To investigate the expression and biological significance of Leptin, Leptin receptor, Vascular Endothelial Growth Factor (VEGF), and CD34 protein in colorectal carcinoma tissues. The expression of Leptin, Leptin receptor, VEGF, and CD34 was detected in 68 cases of colorectal carcinoma tissues, paired para-carcinoma tissues and normal colorectal tissues by Immunohistochemical SP Method. The results and related clinicopathological data were analyzed. The positive rate of Leptin, Leptin receptor, and VEGF was significantly higher in colorectal carcinoma tissues than that in paired para-carcinoma tissues and normal colorectal tissues. The expression of Leptin, Leptin receptor, and VEGF was correlated with grade of tumor differentiation, depth of bowel wall invasion, lymph node metastasis, Dukes stage, distant metastasis, and lympho/vascular tumor embolization. Microvessel density (MVD) value in colorectal carcinoma was significantly higher than that in para-carcinoma tissues and normal colorectal tissues, and the density in para-carcinoma tissues was higher than that in normal colorectal tissues. The expression of Leptin, Leptin receptor, VEGF, and MVD value in colorectal carcinoma was positively correlated. In conclusion, microvessel density value is an important index of the growth, invasion, and metastasis of colorectal carcinoma. The binding of Leptin and Leptin receptor promotes the proliferation of colorectal carcinoma cells. The synergy between Leptin and VEGF accelerates the angiogenesis in colorectal carcinoma and accelerates the invasion and metastasis of the tumor cells.     

Maspin and c-erbB-2 expression in correlation with microvessel density in invasive ductal breast cancer

Maspin is a unique member of the serpin family involved in regulation of cell migration, apoptosis and angiogenesis in breast and prostate cancers. In this study maspin expression in comparison with c-erbB-2 (HER2/neu) oncogene expression and microvessel density was investigated. The examined material included specimens of primary invasive ductal breast cancer derived from 69 patients. They were analyzed immunocytochemically to assess maspin and c-erbB-2 expression, as well as microvessel density using endothelium marker CD31. In the studied cancers, maspin expression in cancer cells was detected in more than half of the cases (50.73%). Although statistically insignificant (p=0.27), maspin expression showed decreasing tendency with the increase of tumor grade. C-erbB-2 oncogene expression was observed in 78.26% of the examined cancers. Statistically significant positive correlation was found between c-erbB-2 expression and tumor grade (p<0.005). Analysis of the dependence between maspin and c-erbB-2 expression exhibited statistically significant inverse correlation (p<0.001). Mean microvessel density (MVD) of the studied cancers was 71.64 (SD=19.36). MVD decreased with the increase of maspin expression, whereas in the cases showing c-erbB-2 overexpression MVD was clearly higher. Both correlations were statistically significant (p<0.005). In conclusion, it could be stated that increase in maspin expression is associated with weaker expression of c-erbB-2 oncogene and lower microvessel density, which implies a significant role of maspin in tumor biology. However, the exact mechanism of maspin action (including its potential role in angiogenesis), as well as the assessment of its prognostic significance in breast cancer require further studies.     

胃癌血管生成素和血管内皮生长因子的表达及其意义

目的探讨血管内皮生长因子(VEGF)和血管生成素(angiopoietin,Ang)在胃癌的表达及其与肿瘤血管生成和临床病理因素的关系。方法采用免疫组化SP法检测84例胃癌和30例癌旁正常组织中VEGF、Ang-1、Ang-2的表达,应用CD34抗体标记微血管内皮细胞,计数微血管密度(MVD),结合临床病理资料进行分析。结果胃癌组织VEGF、Ang-2阳性表达率、MVD值明显高于癌旁正常组织(P(0.05)。VEGF表达与肿瘤大小、侵袭深度、临床分期、淋巴结转移有关(P(0.05),而与患者年龄、性别、组织学类型和分化程度无关,其阳性组的Ang-2阳性表达率、MVD值明显高于阴性组,VEGF的表达与Ang-2、MVD呈正相关。胃癌组织Ang-2表达与肿瘤大小、侵袭深度、淋巴结转移有关(P(0.05),与MVD呈正相关。胃癌Ang-1表达略低于对照组,但无统计学差异(P(0.05),Ang-1的表达与肿瘤侵袭深度和MVD值呈负相关。结论胃癌中VEGF、Ang-2蛋白的过度表达以及Ang-1蛋白的低表达可能在肿瘤血管生成和肿瘤浸润、转移中起重要作用。     

Lung carcinoids. Tumor angiogenesis in relation to clinicopathologic characteristics

OBJECTIVE: To evaluate the prognostic value of carcinoid angiogenesis for the presence of lymph node metastases, histologic subtype and tumor size. STUDY DESIGN: The study group consisted of 72 resected primary lung carcinoids, 57 typical and 15 atypical. TNM staging was performed. The histologic criteria for carcinoids was based on the Flieder classification. Angiogenesis, expressed as tumor microvessel density, was estimated in sections stained with CD34 antibody, according to Weidner's method. RESULTS: The size of carcinoids was related to the histologic type: the average tumor diameter of typical carcinoids was significantly smaller than the average diameter of atypical carcinoids (P = .003, U = 207, Z = -3.023). Atypical carcinoids represented a more aggressive form of tumors than typical carcinoids; patients with typical carcinoids developed lymph node metastases less frequently (10% vs. 33%) as compared to patients with atypical carcinoids; the difference was statistically significant (P = .032). Tumor angiogenesis failed to distinguish the histologic type of carcinoids and did not indicate the presence or absence of regional lymph node metastases; neither did pTN stage or tumor size. CONCLUSION: Angiogenesis is not a determining factor of the metastatic potential of pulmonary carcinoids.     

Increased expression of angiogenic markers in patients with seasonal allergic rhinitis

BACKGROUND: Increased vascularity due to neo-angiogenesis is an essential part of airway remodelling. Vascular endothelial growth factor (VEGF), CD34 and von Willebrand's factor (FvW) are known angiogenic markers. Angiogenesis and airway remodelling has been documented in asthma but not in allergic rhinitis. OBJECTIVE: We aimed to investigate the presence of increased angiogenesis and its relation to angiogenic molecules, namely VEGF, CD34 and FvW, in endothelial cells of nasal mucosa in patients with seasonal allergic rhinitis (SAR), using three different immunohistochemical analysis methods, namely HSCORE, microvessel density (MVD) and vascular surface density (VSD). The findings in allergic rhinitis were compared with the findings in nasal septal deviation (NSD), which is not associated with increased angiogenesis. METHODS: Twenty patients with symptomatic SAR, who were not under treatment, were enrolled in the study. Ten patients with NSD, who needed surgical therapy, served as the control group. Demographic characteristics did not differ between the two groups. Inferior turbinate biopsy was obtained from SAR patients and control patients, under local anaesthesia and during surgery respectively. All biopsies were evaluated for angiogenesis on the basis of VEGF, CD34 and FvW by two blinded histologists using three immunohistochemical analysis methods (HSCORE, MVD and VSD).Results. HSCORE, estimated on the basis of each staining technique, showed statistically significant differences among the two groups (p=0.002; p=0.045; p=0.016, respectively). Anti-CD34 and anti-VEGF showed higher MVD values in SAR when compared to the controls (p=0.038; p=0,009, respectively). No statistically significant difference was found in Anti-FvW-based MVD between SAR patients and controls (p=0.071). The measurements of VSD for FvW and VEGF from nasal biopsy specimens displayed a statistically significant difference between the two groups (p=0.004; p=0.0001, respectively). However, measurement of VSD for CD-34 was not significantly different between the groups (p=0.086). On the other hand, morphometric data obtained by all three methods did not correlated. CONCLUSION: There are a few studies that have investigated the essential role of angiogenesis in the pathogenesis of allergic rhinitis. We conclude that, increased angiogenesis may be as prominent in patients with allergic rhinitis as in patients with non-allergic nasal pathologies and may play an important role in the remodelling of nasal mucosa of subjects with SAR.     

Angiogenesis and the role of bone marrow endothelial cells in haematological malignancies

Increased microvessel density (MVD) has been observed in the bone marrow (BM) of patients with multiple myeloma (MM), acute lymphoblastic leukaemia, acute myeloid leukaemia, and myelodysplastic and myeloproliferative syndrome. The MVD is the net result of cumulative phases of angiogenesis and angio-regression and is as such not an indicator of the ongoing angiogenesis at the time of biopsy. There is, therefore, a need for additional methods that allow the estimation of ongoing angiogenesis. Double immunostainings for CD34 and Ki-67 can be used on paraffin-embedded tissue to determine the endothelial proliferation fraction. The BM endothelial cells, as a component of the BM stroma, have a close interaction with the malignant cells. In MM, for example, they are involved in the specific homing and are a source of paracrine growth factors. Targeting the BM microvessels will not only influence the nutrient and oxygen supply, but will in addition reduce the growth stimuli provided by the EC.     

Evaluation of angiogenesis in normal and lichen planus skin by CD34 protein immunohistochemistry: preliminary findings

Angiogenesis is a critical component of both neoplastic and chronic inflammatory disorders, but whether angiogenesis also occurs in inflammatory skin diseases (such as lichen planus) has yet to be established. This study tests the hypothesis that the development of cutaneous lichen planus is associated with alterations of dermal vascularization (microvessel density, MVD). Thirty cases of cutaneous lichen planus and 40 cases of normal skin were studied. Dermal microvessels were immunostained for CD34 and counted in 10 areas with the highest numbers of microvessels; the mean value represented the final MVD. Compared with normal skin, dermal microvessel density was increased in cutaneous lichen planus [mean, 2.50 (SEM, 0.09) versus 1.39 (SEM, 0.12)]. The microvessel number was higher in the dermal inflammatory infiltrate (intralichenoid infiltrate) and at dermoepidermal junction (below Max-Josef space) compared with adventitial dermis [mean, 2.50 (SEM, 0.09) versus 1.6 (SEM, 0.10)]. The higher MVD values in cutaneous lichen planus suggest a possible link between angiogenesis, and development of these cutaneous lesions. These results provide a morphological evidence of potent angiogenic activity in cutaneous lichen planus, indicating that the local microvasculature may undergo an intense process of inflammation-dependent angiogenesis.     

瘦素及其受体在宫颈癌中的表达和意义

目的探讨瘦素(leptin)及其受体(OB-R)在宫颈癌中的表达与临床病理参数的关系。方法采用免疫组织化学技术检测10例慢性宫颈炎、12例宫颈上皮内瘤样病变、50例宫颈癌中leptin和OB-R的表达,利用CD34标记宫颈癌血管内皮细胞并计算微血管密度(MVD)。结果leptin和OB-R仅在10例慢性宫颈炎、12例上皮内瘤样病变的鳞状上皮层中呈弱阳性表达;50例宫颈癌中Leptin染色( )39例,OB-R染色( )33例;宫颈癌中leptin表达、MVD与肿瘤分化程度、浸润深度和是否远处转移呈正相关(P<0.05),与患者年龄和肿瘤组织学分型无关(P>0.05);OB-R表达与浸润深度和是否远处转移呈正相关(P<0.05),与患者年龄、肿瘤分化程度和组织学分型无关(P>0.05);leptin或OB-R染色( )MVD明显高于染色(-)者。结论Leptin是宫颈癌重要的血管生长因子,瘦素及其受体和MVD与肿瘤的恶性程度密切相关。     

中国人前列腺癌VEGF—C mRNA、VEGFR-3和CD31表达与肿瘤转移的关系

The expressions of VEGF-C mRNA, VEGFR-3 and CD31 were studied in order to investigate the correlation between them and neoangiogenesis, hyperplasia of micro-lymphatics and tumor metastases. 34 cases of prostate cancer tissue and 12 cases of adjacent nontumorous tissue specimens were tested. They were marked by VEGFR-3 and CD31 with immunohistochemistic staining and analyzed with image, the micro-lymphatics count (MLC) and microvessel density (MVD) were counted using Weidner's highest vessel density count method; the expression of VEGF-C mRNA was inspected in situ hybridization. The expression of VEGF-C mRNA was 44.12% positive in 34 cases of prostate cancer, the MLC (8.26 +/- 2.73)mm2 and MVD (74.82 +/- 11.76)mm2 in prostate cancer were significantly higher than those in adjacent nontumorous tissue (MLC, 4.82 +/- 3.48/mm2; MVD, 32.86 +/- 5.41/mm2). In addition, there was a correlation between the expression of VEGF-C mRNA and micro-lymphatics metastases and there was a positive correlation between the expression of VEGFR-3 and CD31. The expressions of VEGF-C mRNA , MLC, MVD in stage III and IV and those who have lymph metastasis were higher than those in stage I and II and those who have no lymph metastasis; the expressions of VEGFR-3 and CD31 in VEGF-C mRNA positive groups were significantly higher than those in negative groups. The difference of histopathologic grading in prostate cancer had no statistical significance. VEGF-C could accelerate the hyperplasia of micro-lymphatics and neoangiogenesis induced by tumor and play an important role in tumor lymph metastases. There was a close correlation between the expressions of VEGFR-3, CD31 and tumor metastases. The increase of MLC and MVD on prostate cancer indicated the hyperplasia of new micro-lymphatics and neoangiogenesis in the tumor tissue, which could also be a signal to determine the tumor metastases in clinic.     

Correlation between angiogenesis, apoptosis and cell proliferation in invasive ductal carcinoma of the breast and their relation to tumor behavior

OBJECTIVE: To investigate the relationship between angiogenesis, apoptosis and cell proliferation in invasive ductal carcinoma of the breast and their relation to tumor behavior. STUDY DESIGN: Microvessels were immunohistochemically labeled with antibody to CD34 in sections from 82 cases of invasive ductal carcinoma. Computerized image analysis was used to evaluate microvessel density (MVD). The authors measured the apoptotic index (AI) using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling technique and proliferating cell nuclear antigen labeling index (PCNA LI) by PCNA immunohistochemistry on serial sections. RESULTS: Statistical analysis revealed a significant inverse correlation between MVD and AI (r = -.313, P = .004) and failed to find a significant correlation between MVD and PCNA LI. There was a significant positive correlation between AI and PCNA LI (r = .393, P = .000). Significant differences in AI between high MVD (> or = 59.9%) and low MVD (< 59.9%) were seen (P < .001), with no appreciable differences in PCNA LI between the two groups. Histologic grade and stage were the only independent prognostic factors in both disease-free and overall survival. CONCLUSION: Angiogenesis in breast cancer may be related to the ability of tumor cells to survive rather than to their proliferative activity. Apoptosis is related to cell proliferation in breast cancer.     

Radiation-induced alterations in microvessel density as predictor of treatment efficiency in oropharyngeal cancer

In this prospective study we have evaluated the predictive role of intratumoral microvessel density (MVD) for the therapeutic response and progression of inoperable oropharyngeal cancer (OPCC) treated with radiotherapy. Thirty-five OPCC patients were enrolled in this study. Biopsies from the primary tumor were taken before and after 20 Gy irradiation. Pathological factors such as histological grade, mitotic activity index and MVD were determined in both samples. Correlations of these factors with response to therapy, progression-free and overall survival were analyzed after a follow-up period of a minimum of 50 months. Objective response and survival was independent of the pretreatment MVD of OPCC. On the other hand, objective response was significantly affected by stage and low posttreatment MVD. Response to irradiation, and therapy-induced low postirradiation MVD were significant indicators of better overall and progression-free survival. We have shown in this small exploratory study that the anti-angiogenic effect of irradiation has a predictive value of the success of radiotherapy in locally advanced OPCC and can be used to select a radioresistant patient population which might require a more aggressive protocol.