Plasma Vascular Endothelial Growth Factor Dysregulation in Defining Aggressiveness of Head and Neck Squamous Cell Carcinoma (original) (raw)
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Background. High circulating vascular endothelial growth factor (VEGF) levels tend to reflect tumor aggressiveness for being associated with tumor progression and prognosis. Measurement of soluble VEGF receptor-1 (sVEGFR-1) may improve diagnostic power of VEGF assay. Methods. This study investigated regulation of plasma VEGF by sVEGFR-1 in 82 patients with head and neck squamous cell carcinoma compared with 32 healthy subjects to obtain information for assay characterization. Results. Normality or abnormality of VEGF/sVEGFR-1secretion patterns was rated into five diagnostic levels from definitely abnormal (likelihood ratios) (LRs = 4–∞) to definitely normal (LRs = 0–0.17). Because of ineffective VEGF regulation, high grade tumor had a greater chance (62.5%) than low grade tumor (20%) in expressing a definitely abnormal pattern and a lower chance to express the normal pattern (P = 0.007). VEGF alone had much lower diagnostic power in differentiating between normal (LRs = 0.3–0.9) and...
2013
Introduction This study aimed to investigate the prognostic and predictive value of serum vascular endothelial growth factor (VEGF) in head and neck squamous cell carcinoma (HNSCC). Method Preoperative and 6-month postoperative serum VEGF levels were measured using a quantitative sandwich enzyme immunoassay technique in 55 consecutive patients with HNSCC and two control groups. The first control group included normal, healthy, age-and sexmatched individuals (n=20), while the second control group included the patients who had history of HNSCC and were free of disease for at least 5 years (n =25). Results The mean baseline serum VEGF concentrations of the 55 patients with HNSCC and the first and the second control groups were 437.86, 42.56, and 48.03 pg/ml, respectively (P<0.001). After a median follow-up of 75 months, 15 patients of the study group developed recurrent disease and 40 patients remained free of disease. The mean preoperative and 6-month postoperative serum VEGF levels for the 40 patients who did not have recurrent disease were respectively 327.69 and 153.50 pg/ml compared to 731.72 and 692.96 pg/ml for the 15 patients with recurrent disease (P <0.001). High (≥540 pg/ml) serum VEGF level was associated with poor overall survival (P < 0.001). Moreover, multivariate analysis showed node stage (P< 0.001) and preoperative serum VEGF level (P=0.020) as significant, independent prognostic factors for overall survival. Conclusion Preoperative or postoperative elevated serum levels of VEGF are highly predictive for disease recurrence and are associated with poor disease-free and overall survival of patients with HNSCC.
Evaluation of tissue and serum VEGF in patients with head and neck carcinoma
Angiogenesis, 1998
Serum vascular endothelial growth factor (VEGF) was measured in 54 cancer patients with head and neck carcinoma. In addition, tumor VEGF was examined by immunohistochemistry in sections of biopsies obtained within 4 weeks to serum sampling in 37 of these patients. Serum VEGF levels were higher in the sera of the tumor patients than in the sera of healthy control subjects (P < 0.005). Patients with stage II-IV tumors showed increased levels of serum VEGF, whereas patients with stage I tumors did not. The receiver operating characteristics (ROC) of serum VEGF were similar to those observed with TPS (tissue protein specific antigen). Immunohistochemistry of tissue sections showed that 24/37 tumors were VEGF positive. No connection was observed between strong VEGF staining of tumor tissue sections and high levels of serum VEGF. We conclude that serum VEGF could be a useful marker for monitoring head and neck carcinoma patients, but that serum and tissue VEGF levels do not appear to c...
Cancers, 2021
Vascular endothelial growth factor (VEGF) is centrally involved in cancer angiogenesis. We hypothesized that pre-therapeutic VEGF levels in serum and plasma differ in their potential as biomarkers for outcomes in head and neck squamous cell carcinoma (HNSCC) patients. As prospectively defined in the study protocols of TRANSCAN-DietINT and NICEI-CIH, we measured VEGF in pretreatment serum and plasma of 75 HNSCC test cohort (TC) patients. We analyzed the prognostic value of VEGF concentrations in serum (VEGFSerum) and plasma (VEGFPlasma) for event-free survival (EFS) utilizing receiver-operating characteristics (ROC). Mean VEGF concentrations in plasma (34.6, 95% CI 26.0–43.3 ng/L) were significantly lower (p = 3.35 × 10−18) than in serum (214.8, 95% CI 179.6–250.0 ng/L) but, based on ROC (area under the curve, AUCPlasma = 0.707, 95% CI 0.573–0.840; p = 0.006 versus AUCSerum = 0.665, 95% CI 0.528–0.801; p = 0.030), superiorly correlated with event-free survival (EFS) of TC patients. Y...
Asian Pacific journal of cancer prevention : APJCP, 2014
To evaluate serum VEGF-A levels in squamous cell carcinoma of head and neck (SCCHN) patients and relationships with response to therapy. Serum VEGF-A levels in patients (n=72) treated with radiotherapy (RT) or radio-chemotherapy (RCT) and controls (n=40) were measured by ELISA. Serum VEGF-A levels of the SCCHN cases were significantly higher (p=0.001) than in healthy controls, and in patients with positive as compared to negative lymph node status (p=0.004). Similarly, patients with advanced stage (Stage III-IV) disease had more greatly elevated levels of serum VEGF-A level than their early stage (Stage I-II) counterparts (p=0.001). In contrast, there was no significant difference (p=0.57) in serum level of VEGF-A in patients with advanced T-stage (T3-4) as compared to early stage (T1-2). Similarly, patients with distant metastasis had no significant (p=0.067) elevation in serum VEGF-A level as compared to non-metastatic disease. However, the non-responder patients had significantly...
Clinical cancer research : an official journal of the American Association for Cancer Research, 1999
Angiogenesis has been linked to increased metastasis formation and decreased overall survival in patients with various tumors, including and neck squamous cell carcinomas (HNSCC). Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. In the present study, we evaluated VEGF expression and microvessel density (MVD), a quantitative means of angiogenesis, in both experimental and clinical models of HNSCC. Analysis of VEGF RNA expression in cell lines of keratinocyte origin [HNSCC, facial skin squamous cell carcinoma (SCC), and transformed but nontumorigenic keratinocytes] and normal skin keratinocytes revealed two VEGF transcripts corresponding to proteins of 165 and 121 amino acids in length, with the transcript for the 165-amino acid species predominating. Six of eight SCC cell lines showed increased levels of one or both transcripts, and seven SCC cell lines and the transformed keratinocyte cell line showed increased protein expression. We then evaluated VEGF ...
Clinical & experimental metastasis, 2000
Vascular endothelial growth factor (VEGF) and its receptors, Flt-1 and flk-1(KDR), constitute an important angiogenic pathway which, under hypoxic conditions, is up-regulated in many solid tumours. We used the monoclonal antibody 11B5, specific for recognizing VEGF expression and the 'VEGF/flk-1(KDR) complex' on tumour endothelium, to assess free VEGF protein expression and VEGF/receptor activated microvessel density (aMVD) in a series of 104 inoperable locally advanced squamous cell carcinomas of the head and neck, treated with chemo-radiotherapy. High VEGF expression in cancer cells was strongly associated with high VEGF/receptor expression in the vasculature. The high VEGF expression and the aMVD were not associated with the standard microvessel density (sMVD), as assessed with the monoclonal antibody anti-CD31 and, were not detected in normal tissue. An increased sMVD, however, was significantly related with the expression thymidine phosphorylase (TP), and also with the ...
2011
Vascular endothelial growth factor-c (VEGF-C) is a potent lymphangiogenic factor and play a crucial role in the regulation of tumor growth and metastasis. Using an ELISA kit, we assessed the circulating levels of VEGF-C in sera from 25 head and neck squamous cell carcinoma (HNSCC) patients as well as from 14 healthy controls. The serum VEGF-C level in HNSCC patients was significantly higher (142.6 ± 41.1 pg/ml ) compared with the healthy controls (35.5 ± 8.3 pg/ml, p<0.005). There was no apparent correlation in serum VEGF-C concentration with the clinico - pathological features such as stage, tumor size, nodal status, distant metastasis and histological grade. This result suggests that the measurement of serum VEGF-C concentration can be an adjuvant test for establishing the diagnosis of HNSCC beside the other tests.
The Turkish Journal of Ear Nose and Throat, 2011
In this study we quantified the expression of vascular endothelial growth factor (VEGF) using quantitative real-time polymerase chain reaction in laryngeal squamous cell carcinoma (LSCC) tissues and evaluated the correlation between the level of VEGF and microvessel density (MVD), and clinicopathological factors. Patients and Methods: Twenty-seven patients with LSCC undergoing total or partial laryngectomy at the Ear, Nose, and Throat and Head and Neck Surgery Department of the Izmir Tepecik Training and Research Hospital between September 2006 and July 2008. There was no VEGF expression in two patients that were excluded from the study. Twenty-five patients (24 males, 1 female; mean age 61 years; range 43 to 82 years) were included in this study, but MVD levels of 10 patients could not be determined. Results: As defined by the 2003 American Joint Committee on Cancer (AJCC) TNM classification, seven patients (28%) were stage 1, six patients (24%) were stage 2, four patients (16%) were stage 3, and eight patients (32%) were stage 4. Thirteen patients (52%) had well-differentiated (G1) tumors, and twelve had moderately differentiated tumors. Among the 15 patients for whom the MVD was determined, the median value was 48, with a (range 13-78; vessels / 3.76 mm 2). Among the 25 patients for whom the VEGF level was determined, the median value was 0.035 vessels / 3.76 mm 2 (range 0.010-0.127). Conclusion: We could not find a statistical correlation between clinicopathological factors and either VEGF or MVD. Our study demonstrates that VEGF is expressed by LSCC.
British Journal of Oral and Maxillofacial Surgery, 2008
Background: Saliva is an enriched milieu containing biologically active proteins, including growth factors and cytokines. The endothelial growth factor family of proteins is important for the development of blood and lymphatic vessels in a healthy individual but also can aide tumour growth. The aim of this study is to develop an independent normative database of values of salivary VEGF in a healthy population and to test the hypothesis that values would be raised in the saliva of patients with oral cancer. Methods: Twenty-one participants (12 males and 9 females) of whom 14 were healthy and 7 had oral squamous cell carcinoma took part in this study. An immunoassay was employed to quantify a range of specific vascular endothelial and lymphatic endothelial growth factors in various body fluid compartments (blood, saliva). This was correlated to tumour factors and patient outcomes. Results: The mean salivary levels and serum VEGF A 165 levels were significantly correlated in the sample as a whole. Additionally, both saliva and serum VEGF A 165 levels were significantly correlated with age. There were significant differences in the salivary and serum levels of the control group and the cancer group. Conclusion: We present independent normative data on the levels of endothelial growth factor in the saliva of a healthy control population. We also suggest the use of simple non-invasive tests in helping to predict head and neck tumour biology and outcomes.