Immunohistochemical Expression Of Vascular Endothelial Growth Factor Research Articles

Vascular Endothelial Growth Factor Expression in Breast Carcinoma and its Association with Expression of Estrogen Receptors, Progesterone Receptors and HER-2/neu and Molecular Subtypes

Background: The management of breast carcinoma depends on several molecular markers and tumor stages. In the last decades, estrogen receptors (ER), progesterone receptors (PR), and HER-2/neu have shown good therapeutic responses. Among other molecular markers, vascular endothelial growth factor (VEGF) is becoming more widely used as a prognostic indicator in patients with breast carcinoma. Anti-VEGF therapy already has been proven as an effective chemotherapeutic agent in some other carcinomas. The study aimed to find out the immunohistochemical expression of Vascular Endothelial Growth Factor (VEGF) in breast carcinoma and its possible correlation with the expression of ER, PR, and HER-2/neu and molecular subtypes to evaluate its prognostic value. Material & Methods: This study was conducted in the Department of Pathology, BIRDEM General Hospital, Dhaka, from March 2018 to January 2020. In this study, 45 diagnosed cases of breast carcinoma were enrolled. Slides of all cases were stained with ER, PR, HER-2/neu, and VEGF antibodies following the avidin-biotin-peroxidase staining method. Results: Among 45 cases, 60% showed positive immunohistochemical expression of VEGF. Most of these cases (71.1%) were ER/PR positive. VEGF did not show a significant association with other molecular markers or molecular subtypes. Conclusion: Although, the potential prognostic value of VEGF has not been confirmed. Based on the findings of the current study, it can be assumed that VEGF plays an important role in the pathogenesis of breast cancer. So, it may serve as a useful biomarker for immuno-targeting therapy in patients with breast cancer.

Immunohistochemical Expression of Vascular Endothelial Growth Factor in Different Histomorphological Types of Breast Carcinoma.

Background: Breast carcinoma is a heterogenous disease that represent a major health problem in Bangladeshi population. Several molecular markers have been detected over the past several decades, that are important in clinical aspects of breast carcinoma. Most recently, Vascular Endothelial Growth Factor (VEGF) is emerging as a prognostic marker in patients with several types of carcinoma including breast carcinoma. Many anti-angiogenic therapies targeting VEGF has been proven effective in many carcinomas. Objectives:This study was aimed to determine the expression of VEGF in different histomorphological types of breast carcinoma in an attempt to clarify its potential clinical outcome. Materials and Methods: This study was conducted in the Department of Pathology, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM) General Hospital, Dhaka from March 2018 to January 2020. In this study, 45 diagnosed cases of breast carcinoma were enrolled. Histopathological slides of all cases were re-evaluated. Thin sections were taken on coated slides from each paraffin block and immunohistochemical staining was done with VEGF antibody. Results: Among 45 cases, 73.3% cases were invasive ductal carcinoma and 13.3% cases were invasive lobular carcinoma. The immunohistochemical expression of VEGF was positive in 60% cases. In this study, 100% cases of in-situ ductal carcinoma, 83.3% cases of invasive lobular carcinoma and 57.6% cases of invasive ductal carcinoma showed overexpression of VEGF. However VEGF expression did not show significant association with histomorphological types. Conclusion: VEGF expression was found in 60% of breast carcinoma cases. It may serve as a potential therapeutic target for the management of breast carcinoma. KYAMC Journal Vol. 13, No. 01, April 2022: 9-12

Significance of Vascular Endothelial Growth Factor Expression in the Bladder Urothelial Carcinoma and Its Association with Tumor Grade and Invasiveness

Background & Objective: Vascular Endothelial Growth Factor (VEGF) is one of the newer molecular markers that acts as a central mediator of tumor angiogenesis and is essential for tumor growth, progression, and metastasis. So anti-angiogenic drugs can be used as anticancer therapy. Treatments with anti-VEGF (Bevacizumab) therapy have been proved to improve relapse-free survival in many tumors. Urinary bladder tumor has become emerging cancer globally among elderly individuals. So, the identification and development of novel biomarkers for effective treatment of urinary bladder carcinoma is essential. The present study aimed to investigate the immunohistochemical expression of VEGF in urothelial carcinoma of urinary bladder and to assess its association with tumor grade and muscle invasiveness.Methods: This cross-sectional study was conducted in the Department of Pathology, Chittagong Medical College, Chattogram from September 2018 to August 2020. Fifty-six formalin-fixed paraffin-embedded tissue blocks of urinary bladder carcinoma were prepared for both histopathological and immunohistochemical examination. Each slide was evaluated by at least two pathologists.Results: Weak to strong positive expression of VEGF were observed in 52 cases (92.86%). The proportion of tumors positive for VEGF expression was higher among patients with high grade and non-muscle invasive bladder carcinoma. Conclusion: We found that VEGF expression has a significant association with tumor grade and an inverse association with muscle invasion. These findings may be useful for selecting the subset of patients likely to respond to anti-VEGF targeted therapy.

Nasal expression of the vascular endothelial growth factor and its receptors is reduced by mepolizumab in chronic rhinosinusitis with nasal polyposis

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a phenotype of chronic rhinosinusitis characterized by the presence of nasal polyps. To date, medical therapy and surgery can manage the disease in most cases. 1 Fokkens W.J. Lund V.J. Hopkins C. et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology. 2020; 58: 1-464 Google Scholar However, despite improvements in surgical techniques, CRSwNP is characterized by relapses in severe cases, thus leading to the study of biologic drugs such as mepolizumab, antagonizing interleukin (IL)-5. Experimental and clinical evidence demonstrates that CRSwNP is driven by a type 2 immune response and displays eosinophil infiltration, mucosal inflammation, and hyperplasia of the epithelium. 2 Bachert C. Marple B. Hosemann W. Cavaliere C. Wen W. Zhang N. Endotypes of chronic rhinosinusitis with nasal polyps: pathology and possible therapeutic implications. J Allergy Clin Immunol Pract. 2020; 8: 1514-1519 Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar Furthermore, it has been described that vascular endothelial growth factor (VEGF) is strongly up-regulated in the mucosa of patients with CRSwNP, promoting edema and epithelial cell growth in nasal polyps when compared with normal mucosa. 3 Wittekindt C. Hess A. Bloch W. Sultanie S. Michel O. Immunohistochemical expression of VEGF and VEGF receptors in nasal polyps as compared to normal turbinate mucosa. Eur Arch Otorhinolaryngol. 2002; 259: 294-298 Crossref PubMed Scopus (56) Google Scholar Notably, other reports found that IL-5 stimulates VEGF production, which may influence immune cells’ activity in inflammatory conditions. 4 Puxeddu I. Ribatti D. Crivellato E. Levi-Schaffer F. Mast cells and eosinophils: a novel link between inflammation and angiogenesis in allergic diseases. J Allergy Clin Immunol. 2005; 116: 531-536 Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar

Significance of Vascular Endothelial Growth Factor Expression in the Bladder Urothelial Carcinoma and Its Association with Tumor Grade and Invasiveness.

Background & Objective:Vascular Endothelial Growth Factor (VEGF) is one of the newer molecular markers that acts as a central mediator of tumor angiogenesis and is essential for tumor growth, progression, and metastasis. So anti-angiogenic drugs can be used as anticancer therapy. Treatments with anti-VEGF (Bevacizumab) therapy have been proved to improve relapse-free survival in many tumors. Urinary bladder tumor has become emerging cancer globally among elderly individuals. So, the identification and development of novel biomarkers for effective treatment of urinary bladder carcinoma is essential. The present study aimed to investigate the immunohistochemical expression of VEGF in urothelial carcinoma of urinary bladder and to assess its association with tumor grade and muscle invasiveness.Methods:This cross-sectional study was conducted in the Department of Pathology, Chittagong Medical College, Chattogram from September 2018 to August 2020. Fifty-six formalin-fixed paraffin-embedded tissue blocks of urinary bladder carcinoma were prepared for both histopathological and immunohistochemical examination. Each slide was evaluated by at least two pathologists.Results:Weak to strong positive expression of VEGF were observed in 52 cases (92.86%). The proportion of tumors positive for VEGF expression was higher among patients with high grade and non-muscle invasive bladder carcinoma. Conclusion:We found that VEGF expression has a significant association with tumor grade and an inverse association with muscle invasion. These findings may be useful for selecting the subset of patients likely to respond to anti-VEGF targeted therapy.

Immunohistochemical Expression of Vascular Endothelial Growth Factor in Ovarian Surface Epithelial Neoplasms and its Association with Histological Type, Grade, Clinical Stage and Tumour Metastasis

Introduction: Ovarian carcinoma is one of the most common gynaecologic cancers and remains the leading cause of death as the patients are diagnosed at the advanced stage of the disease. Vascular Endothelial Growth Factor (VEGF), a promoter of angiogenesis, participates in multiple mechanisms to promote ovarian cancer cell growth, angiopoiesis and distant metastasis. So, it is a promising target for antiangiogenic therapy in management and downstaging of ovarian cancer. Aim: To evaluate the immunohistochemical expression of VEGF in different surface epithelial neoplasms of ovary and compare it with histological type, grade and stage in malignant cases. Materials and Methods: This was an observational cross-sectional study conducted from August 2018 to January 2020. Total 50 consecutive cases of surface epithelial ovarian neoplasms received in Pathology Department of Srirama Chandra Bhanja (SCB) Medical College, Cuttack were examined for expression of VEGF by Immunohistochemistry (IHC). Data was examined to find association of VEGF expression with demographic profile, grade, stage and were analysed statistically using Statistical Package for the Social Sciences (SPSS) software version 21.0. Statistical significance was tested by using Pearson’s chi-square test. The p<0.05 was considered significant. Results: Total 50 cases of ovarian surface epithelial neoplasms of different types and grade were included in the study. A 42 of the 50 cases (84%) showed VEGF expression. Out of the 42 positive cases, 18 were high VEGF expressors and 24 were low VEGF expressors. The VEGF expression was significantly higher in carcinomas as compared to benign and borderline neoplasms and also in high grade malignancies in comparison to low grade (p≤0.001). Conclusion: The study shows that the differential expression of VEGF in different ovarian epithelial neoplasms which can be a diagnostic and prognostic tool and can be applied as a VEGF targeted therapy in certain group of patients.

INVESTIGATION OF SFLT-1 AND VEGF EXPRESSION IN NORMOTENSIVE AND PREECLAMPTIC PLACENTA. AN IMMUNOHISTOCHEMICAL STUDY

Objectives: The pathogenesis of preeclampsia is still not clear, but endothelial dysfunction believed to be one of the most encountered problems during placenta development in preeclamptic patients. Both vascular endothelial growth factor (VEGF) and its antagonist, soluble Fms-Like tyrosine kinase-1 (sFlt-1), have roles in vascular function. In this study, we have investigated immunohistochemical expression of VEGF and sFlt-1 in term placenta of normotensive and preeclampsia patients. Methods: Totally twenty term placentas were obtained from pregnant women of which 10 preeclampsia patient and 10 normotensive. Placentas were dissected and tissue samples were subjected to routine tissue processing protocol, then embedded in paraffin blocks. Serial sections were obtained from paraffin blocks and stained with H&E and PAS for routine histopathology. VEGF and sFlt-1 immunohistochemistry was performed to the sections. Results: When compared to control group, severe pathological changes were observed in preeclamptic placentas. Increase in number of syncytial knots and intervillous bridges, hemorrhage in interstitium, dilatation and congestion in villous capillaries, increase in fibrin accumulation in villus stroma, and increase in thickening of basement membrane were very clear. VEGF expression was significantly higher in normotensive placentas compared to preeclamptic. On the other hand, sFlt-1 expression was significantly increased in preeclamptic placentas. Conclusions: When the VEGF and sFlt-1 expression was considered, higher expression of sFlt-1 at preeclampsia, but decrease in VEGF expression, might be related to endothelial dysfunction in preeclampsia. Overall, this study demonstrates, imbalance between VEGF and sFlt-1 is one of the major reason of endothelial dysfunction in preeclamptic placenta.

Immunohistochemical Expression of Vascular Endothelial Growth Factor as a Prognostic Marker for Canine Mast Cell Tumors

Strong to moderate vascular endothelial growth factor (VEGF) expression may be a negative prognostic factor in canine mast cell tumors (MCTs). This study set out to determine the prognostic value of combined analysis of VEGF-A immunoreactivity, clinical presentation, patient staging, and tumor histologic grade in canine MCTs. In this study, intense VEGF staining was significantly associated with decreased survival (P = .025). Immunohistochemical expression of VEGF is not routinely employed as a prognostic factor in canine MCT workup. However, results of this study support the inclusion of this marker in the MCT prognostic panel. Investigation of VEGF expression may assist in the development of anti-VEGF drugs.

The Effect of EGF on VEGF expression on Submandibular Salivary Gland of Albino Rats Receiving Doxorubicin

Background: Vascular endothelial growth factor (VEGF) has two prominent biological effects of inducing mitogenesis and migration of vascular endothelial cells and to produce permeability on the microvasculature. Epidermal growth factor (EGF), known by its mitogenic activity on different types of cells, could induce the proliferation and differentiation of the epithelial cells and stimulate its regeneration. Doxorubicin (DXR) is a widely used anticancer drug and is one of most commonly used chemotherapeutic drugs, however it may cause some serious complications such as toxicity in various tissues in the body.Aims: The present study aims to investigate the effect of EGF on the VEGF immunoexpression in submandibular salivary gland tissue of rats receiving Doxorubicin (DXR).Methods and Material: 30 male Albino rats, two months old and weighing 200-250 gm body weight, were divided equally into three groups as follows: Group I (control group). Group II: rats received 20 mg/kg body weight DXR as a single intra peritoneal injection. Whereas, group III: rats received the same dose of DXR and on the next day they were injected intraperitoneally with EGF in a daily dose of 10μg/kg body weight for 7 consecutive days.Submandibular salivary glands were dissected out and processed for histological investigation and immunohistochemical localization of VEGF in the glandular tissue.Statistical analysis used: ANOVA was used to compare the mean area percentage of VEGF immunostaining among the specimens of different groups followed by Tukey’s Multiple Comparison Test.Results: VEGF expression in submandibular salivary glands of rats significantly decreased after DXR injection. However, daily intraperitoneal injections of EGF restored normal levels of VEGF expression in the glandular tissue.Conclusions: EGF preserved glandular architecture after DXR injection and consequently the immunohistochemical expression of VEGF in the glands to approximately the normal level.

Молекулярные и клеточные эффекты внутрисуставного введения бетаметазона при экспериментальном остеоартрите

The objective of the study was to assess articular cartilage (AC) and subchondral bone (SCB) remodeling, expression of matrix metalloproteinase 9 (MMP-9) in tissues, vascular endothelial growth factor (VEGF) in experimental osteoarthritis (OA). Material and methods Experimental comparative study was conducted on 12 outbred guinea pigs of both sexes aged 28–30 weeks that were divided into 2 groups of 6 animals each. An injury to the knee joints of hind limbs of control and experimental animals was mechanically simulated by closed scarification using a sterile needle. No treatment was provided for controls. Experimental animals were given an intraarticular injection of betamethasone (BMZ) of 0.1 mg/kg every two weeks after two weeks of injury. Two subjects of each group were euthanized at 30, 45, 60 days and knee samples collected. Immunohistochemical expression of VEGF and MMP-9 was determined in tissues. Results A statistically significant decrease in VEGF positive chondrocytes and precipitate density, an increase in positive chondrocytes and intensity of tissue response to MMP-9 as compared to those in controls was observed in BMZ animals at 30 days of experiment. A statistically significant decrease in VEGF positive cells and precipitate density, an increase in VEGF positive chondrocytes as compared to those in controls were observed in BMZ animals at 45 days of experiment. Significant reduction in VEGF positive cells and deposit density, significantly higher density of MMP-9 positive precipitates as compared to those in controls were noted at 60 days of BMZ injections. Conclusion Intraarticular injections of BMZ demonstrated a negative effect on AC and SCB with articular tissue remodeling initiated through activation mechanisms of extracellular matrix degradation, as evidenced by high expression of MMP-9. BMZ was shown to block pathological angiogenesis via VEGF inhibition.

Nitric oxide synthase and VEGF expression in full-term placentas of obese women.

An adequate placental vascularization allows the proper development of the fetus and it is crucial for the gestational success. A number of factors regulate angiogenesis, including vascular endothelial growth factor (VEGF), which induces the synthesis of nitric oxide (NO), a potent vasodilator produced by three different nitric oxide synthase (NOS) isoforms. NO is essential to maintain a low vascular resistance in the fetoplacental circulation, although at high concentrations, it may combine with excess superoxide to produce peroxynitrite, which reacts with proteins giving rise to nitrotyrosine. Since obesity, whose incidence is increasing worldwide, is characterized by a low-grade inflammatory state and increased levels of oxidative and nitrative stress, both affecting placental function, our aim was to evaluate the expression of VEGF, eNOS, and iNOS in full-term placentas obtained from normal weight and pre-pregnancy obese women by means of immunohistochemistry and real-time PCR. Moreover, we assessed the NO levels and the nitrotyrosine immunoexpression in the same sample groups. Our results show a significantly higher immunohistochemical expression of VEGF and eNOS in the endothelium of placentas from obese women than in controls, whereas the immunoexpression of iNOS was comparable in the two groups. These data agree with those of the gene expression analysis, thus suggesting the possible existence of a compensatory mechanism for changes in placental blood flow associated with obesity. As concerns nitrotyrosine and NO levels, we observed a significant increase in placental tissue from obese women which may contribute to the development of metabolic and cardiovascular diseases both in the mother and the offspring.

Angiogenesis in odontogenic keratocyst and dentigerous cyst: Evaluation of JunB and VEGF expression

Nowadays, different clinical behaviors of odontogenic cysts, little information about their biological agents, importance of diagnosis, and early diagnosis of these lesions have encouraged the researchers to conduct new studies. JunB acts as a regulator of vascular endothelial growth factor (VEGF) protein production and affects vessel proliferation and tissue angiogenesis. Hence, this study was conducted to compare angiogenesis through VEGF and JunB expression in odontogenic keratocysts (OKCs) and dentigerous cysts (DCs). A total of 25 paraffin blocks of OKCs and 25 DCs were included in this experimental descriptive cross-sectional study, and immunohistochemical expression of VEGF and JunB was evaluated. Percentage and score of expression were recorded for each sample, and independent t-test, Mann-Whitney U, and Spearman statistical tests were run to analyze the data. The statistical significance level was set at <0.05. From 50 studied samples, 39.6% belonged to women and 60.4% belonged to men, with mean age of 34.2 ± 1.7 years. The mean percentages of JunB expression were 52.88 ± 17.35 and 74.6 ± 18.55 for DC and OKC samples, respectively. This expression was significantly higher in OKC than DC, and it had significantly higher scores as well (P = P = 0.0001 and 0.00033, respectively). The means of VEGF were 20.2% ±11.86 and 52.6% ±19.98 in DC and OKC samples, respectively. The mean VEGF expression was significantly higher in OKC than DC (P = 0.045), and it had significantly higher scores, too (P = 0.000). Furthermore, there was a significant correlation between VEGF and JunB expression in the studied samples (rs = 0.3 and P = 0.005). Based on the results of this study, it seems evaluation of angiogenesis through JunB expression can be helpful in the prediction of more aggressive behavior in pathologic lesions such as OKC.

EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN ORAL SQUAMOUS CELL CARCINOMA: A CLINICOPATHOLOGICAL STUDY

INTRODUCTION: Oral squamous cell carcinoma (OSCC) is one of the most widely occurring cancer worldwide. It represents the tenth most common cancer affecting the world population. Like all other tumors, malignant epithelial cells of the OSCC need adequate blood supply and thus tend to recruit new blood vessels by Angiogenesis (the formation of new vessels by sprouting of the pre-existing endothelium). The major regulators of blood and lymph vessel development are the members of the Vascular Endothelial Growth Factor (VEGF) family. These are multifunctional proteins mainly involved in normal and pathologic angiogenesis. Accordingly, there is an increasing interest in evaluating the diagnostic and prognostic value of VEGF family OBJECTIVES: To evaluate the expression of VEGF-A in OSCC and to correlate it with both histopathological grading and clinical data. MATERIALS AND METHODS: This study includes 20 patients with OSCC. The lesions of concern were clinically examined and biopsied. The tissue biopsies, as well as five negative control specimens, were processed and paraffin sections were prepared. Hematoxylin and eosinstained sections were examined for grading of the carcinoma. The immunohistochemical expression of VEGF was evaluated by the use of Anti-VEGF-A Antibody using the Strept-Avidin-Biotin method on paraffin sections. Immunohistochemical results were evaluated using an image analyzer. Results were recorded and statistically analyzed and correlated with both clinical and histological grading of the tumors. RESULTS: The expression of VEGF was found to be significantly related to the grade of differentiation of the tumor, where the poorer the differentiation, the more the expression the antibody. On the contrary, no significant relation between VEGF expression and clinical data was found. CONCLUSIONS: The expression of VEGF is of a great value as a means of diagnosis concerning histological grading of the tumor, but cannot be used as a sole method for evaluating the case prognosis

Tympanomastoid cholesterol granulomas: Immunohistochemical evaluation of angiogenesis.

This study investigates the immunohistochemical expression of vascular endothelial growth factor (VEGF) and CD34 in patients treated for middle ear and mastoid cholesterol granulomas to evaluate the angiogenesis and vascularization of this type of lesion. A correlation between the immunohistochemical data and the radiological and intraoperative evidence of temporal bone marrow invasion and blood source connection was performed to validate this hypothesis. Retrospective study. Immunohistochemical expression of VEGF and CD34 in a group of 16 patients surgically treated for cholesterol granuloma was examined. Middle ear cholesteatomas with normal middle ear mucosa and external auditory canal skin were used as the control groups. The radiological and intraoperative features of cholesterol granulomas were also examined. In endothelial cells, there was an increased expression of angiogenetic growth factor receptors in all the cholesterol granulomas in this study. The quantitative analysis of VEGF showed a mean value of 37.5, whereas the CD34 quantitative analysis gave a mean value of 6.8. Seven patients presented radiological or intraoperative evidence of bone marrow invasion, hematopoietic potentialities, or blood source connections that might support the bleeding theory. In all of these cases there was computed tomography or intraoperative evidence of bone erosion of the middle ear and/or temporal bone structures. The mean values of VEGF and CD34 were 41.1 and 7.7, respectively. High values of VEGF and CD34 are present in patients with cholesterol granulomas. Upregulation of VEGF and CD34 is indicative of a remarkable angiogenesis and a widespread vascular concentration in cholesterol granulomas. 3b. Laryngoscope, 127:E283-E290, 2017.

Immunohistochemical expression of vascular endothelial growth factor (VEGF) in prostate adenocarcinoma

Introduction: Clinical and morphological prognostic factors for PCa are Gleason score, TNM classification and lymph node invasion. VEGF is an inducer of angiogenesis, which plays an important role in tumor growth and metastasis. It was shown that PCa cells express VEGF. Aim: The aim of this paper is to analyze the immunohistochemical expression of VEGF in prostate adenocarcinoma and correlate it with the clinical and morphological prognostic factors in the sample of patients treated at the Clinical Hospital Center 'Dr Dragiša Mišović' in Belgrade. Material and methods: The operative material from 20 cases of prostate adenocarcinoma was used. TNM classification from 2002 was used to determine the stage of the tumor, and Gleason score from 2009 was applied to determine the grade. Immunohistochemical staining of prostate adenocarcinoma was semiquantitatively evaluated. Results: Expression of VEGF was present in all analyzed adenocarcinoma of the prostate. In fifteen cases (75%) of the analyzed twenty cases, immunostaning was diffuse, while in five cases it was moderate (25%). A statistically significant correlation was noted between diffuse expression of VEGF and higher Gleason score (p < 0.01). Frequency of diffuse expression of VEGF was higher in cases with the presence of lymphatic node metastasis and TNM stage III and IV, but the results were not statistically significant. Conclusion: Diffuse expression of vascular endothelial growth factor (VEGF) is more often observed in prostate cancer (PCa) with higher Gleason score, higher TNM stage and lymph node invasion, in the sample of patients treated at the Clinical Hospital Center 'Dr Dragiša Mišović' in Belgrade, all consistent with previous studies.

EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR DURING HEALING OF EXTRACTION SOCKETS IN DIABETIC RATS

Introduction: Vascular endothelial growth factor (VEGF) is one such candidate. It functions as an endothelial cell mitogen, chemotactic agent, and inducer of vascular permeability. Other angiogenic growth factors such as basic fibroblast growth factor (bFGF) and transforming growth factor β (TGF-β) have been described, but VEGF is unique for its effects on multiple components of the wound healing cascade, including angiogenesis and recently shown epithelization and collagen deposition. VEGF is produced by many cell types that participate in wound healing: endothelial cells, fibroblasts,smooth muscle cells, platelets, neutrophils, and macrophages. . Objectives: To evaluate the expression of VEGF during healing of extracted sockets in diabetic rats. Materials and methods: 24 adult male rats aged about 6 months and weighing about 250 gms were divided into 2 groups; Group I (12 rats) non diabetic and Group II (12 rats) diabetic. For study group, the rats were fasted overnight and diabetes was induced by a single intra peritoneal injection of streptozotocin 60 mg/kg body weight in 0.1 M citrate buffer. All animals, were exposed to surgical wounds (extracted lower right first molar). They were sacrificed as follows 4 rats from each group at intervals of 3 days, 7 days, 21 days after extraction for immunohistochemical study. Results: In the present study, immunohistochemical expression of VEGF was detected as brown cytoplasmic reaction. All the examined cases showed positive results for VEGF with different scores. Conclusions: these results demonstrated the expression of VEGF in diabetic rats during healing of extraction sockets significantly higher than control group in late periods.

Attenuation of choroidal neovascularization by histone deacetylase inhibitor.

Choroidal neovascularization (CNV) is a blinding complication of age-related macular degeneration that manifests as the growth of immature choroidal blood vessels through Bruch’s membrane, where they can leak fluid or hemorrhage under the retina. Here, we demonstrate that the histone deacetylase inhibitor (HDACi) trichostatin A (TSA) can down-regulate the pro-angiogenic hypoxia-inducible factor-1α and vascular endothelial growth factor (VEGF), and up-regulate the anti-angiogenic and neuro-protective pigment epithelium derived factor in human retinal pigment epithelial (RPE) cells. Most strikingly, TSA markedly down-regulates the expression of VEGF receptor-2 in human vascular endothelial cells and, thus, can knock down pro-angiogenic cell signaling. Additionally, TSA suppresses CNV-associated wound healing response and RPE epithelial-mesenchymal transdifferentiation. In the laser-induced model of CNV using C57Bl/6 mice, systemic administration of TSA significantly reduces fluorescein leakage and the size of CNV lesions at post—laser days 7 and 14 as well as the immunohistochemical expression of VEGF, VEGFR2, and smooth muscle actin in CNV lesions at post-laser day 7. This report suggests that TSA, and possibly HDACi’s in general, should be further evaluated for their therapeutic potential for the treatment of CNV.

Expression of vascular endothelial growth factor in oral squamous cell carcinoma.

ObjectivesThe goal of this study was to determine the correlation of clinicopathological factors and the up-regulation of vascular endothelial growth factor (VEGF) expression in oral squamous cell carcinoma.Materials and MethodsImmunohistochemical staining of VEGF and quantitative real-time polymerase chain reaction (RT-PCR) of VEGF mRNA were performed in 20 specimens from 20 patients with oral squamous cell carcinoma and another 20 specimens from 20 patients with carcinoma in situ as a controlled group.ResultsThe results were as follows: 1) In immunohistochemical study of poorly differentiated and invasive oral squamous cell carcinoma, high-level staining of VEGF was observed. Significant correlation was observed between immunohistochemical VEGF expression and histologic differentiation, tumor size of specimens (Pearson correlation analysis, significance r>0.6, P<0.05). 2) In VEGF quantitative RT-PCR analysis, progressive cancer showed more VEGF expression than carcinoma in situ. Paired-samples analysis determined the difference of VEGF mRNA expression level between cancer tissue and carcinoma in situ tissue, between T1 and T2-4 (Student's t-test, P<0.05).ConclusionThese findings suggest that up-regulation of VEGF may play a role in the angiogenesis and progression of oral squamous cell carcinoma.

Immunohistochemical Expression of VEGF in Relation to Other Pathological Parameters of Breast Carcinoma

Background: Several molecular markers have been detected that are important in clinical aspect of malignancies especially in breast cancer. More recently, the expression of vascular endothelial growth factor (VEGF), the most potent endothelial cell mitogen and also a regulator of vascular permeability, is emerging as a prognostic marker in patients with several types of cancer including breast cancer. This study assessed the expression of VEGF in a series of breast cancers in correlation with HER-2/neu and steroid receptors (ER and PR) in standard clinicopathological parameters in an attempt to clarify its potential clinical importance in Iraqi females of Middle Euphrates area. Findings: The present investigation was performed over a period starting from September 2011 through September 2012. Formalin-fixed, paraffin-embedded blocks from 52 patients with breast cancer (44 ductal and 8 lobular carcinoma) were included in this study. A group of 20 patients with fibroadenoma was included as a comparative group, and 20 samples of normal breast tissue sections were used as controls. Labeled streptavidin-biotin (LSAB+) complex method was employed for immunohistochemical detection of VEGF, HER-2/neu, ER and PR. The detection rate of VEGF, HER-2/neu, ER and PR was 59.62%, 36.96%, 34.62% and 36.54% respectively. There was a significant difference in immunoexpression between ductal and lobular carcinoma, but not significantly different among tumor sizes, tumor grades, axillary lymph node involvement and age of the patients. However, VEGF was positively correlated with tumor grade, tumor size, nodal involvement and HER-2/neu, but negatively correlated with ER and PR, which show the most unfavorable biopathological profile. Conclusion: VEGF overexpression play an important role in pathogenesis of breast carcinoma evolution, as its positivity associated with biologically aggressive tumors, so incorporation of this biomarker with other parameters into a prognostic index will more accurately predict clinical outcome and determine the effects of anti cancer therapy.

Correlation between selected angiogenic markers and prognosis in pediatric adrenocortical tumors: Angiogenic markers and prognosis in pediatric ACTs

Background/PurposePediatric adrenocortical tumor (ACT) remains a challenging disease. Tumor weight and disease stage are still the most used indicators to prognosis and guidance of clinical decisions. Histology has not added meaningful data for risk stratification and management. ACT is metabolically active, highly vascularized, locally invasive and has the propensity to produce distant metastasis. Our objective was to correlate the expression of vascular endothelial growth factor (VEGF) and intratumoral microvessel density (MVD) with clinical and prognostic aspects in pediatric ACT. ProcedureIn 27 tumors, immunohistochemical expression of VEGF, CD105 (endoglin) and CD34 was analyzed. MVD was determined by CD34 and CD105 antibodies. MVD and VEGF expression was correlated with clinical characteristics and outcome. Normal pediatric glands were used as controls. ResultsEndoglin MVD was significantly higher and CD34 MVD was significantly lower in ACT than control. The VEGF expression did not differ between groups. Cytoplasmic staining for endoglin was correlated with hypertension in ACT. Endoglin MVD greater than 1 mv/field, CD34 MVD less than 32 mv/field and VEGF expression levels above 4.8% were associated with clinical and biological indicators of poor prognosis. ConclusionsEndoglin and CD34 MVD values are potential histological markers to refine the histologic classification of pediatric ACT.