Anna Sitkiewicz

LOCAL SERUM LEVELS OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN INFANTILE HEMANGIOMA: INTRIGUING MECHANISM OF ENDOTHELIAL GROWTH

UNLABELLED The pathogenesis of hemangiomas still remains poorly understood. Dysregulation of angiogenesis has been proposed to play a central role in hemangioma pathogenesis. The aim of our study was to determine the peripheral and local serum levels of VEGF in patients with hemangiomas and vascular malformations. MATERIAL AND METHODS The study group consisted of 52 children with infantile hemangioma (33 with proliferative lesions, 19 with involuting lesions), 14 children with vascular malformations and 36 healthy children. VEGF serum levels were analyzed by an ELISA assay and the values between the groups were compared. RESULTS The serum peripheral VEGF concentrations in children with proliferative hemangiomas were significantly higher than in patients with involuting hemangiomas, vascular malformations and controls. There was no correlation between the measured cytokine level, hemangioma size, and the age of the patients. The local serum VEGF levels in 29 children with hemangiomas were distinctly lower than in the peripheral blood, both in 20 proliferating hemangiomas (p<0.0001) and 9 involuting ones (p=0.007); and the difference between females and males was non-significant (NS p=0.06). CONCLUSIONS (1) VEGF serum levels vary in the different phases of hemangioma growth and may help to distinguish hemangiomas from vascular malformations; (2) obtained local results may support the intrinsic theory of endothelial cell proliferation in hemangiomas.

SERUM LEVELS OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND BASIC FIBROBLASTIC GROWTH FACTOR IN CHILDREN WITH HEMANGIOMAS AND VASCULAR MALFORMATIONS--PRELIMINARY REPORT

Abstract:  Impaired balance between proangiogenic and antiangiogenic factors has been implicated in the development of hemangiomas. Elevated vascular endothelial growth factor serum levels and basic fibroblastic growth factor urine levels in patients with proliferating hemangiomas were reported. However, whether these growth factors can be used for the differential diagnosis of vascular anomalies or assessment of the clinical course of hemangiomas has yet to be determined. We report here our preliminary results of serum vascular endothelial growth factor and basic fibroblastic growth factor levels as an aid in the diagnosis of hemangiomas and in the follow up of patients with this lesion. Twenty two children with infantile hemangioma (13 with proliferating hemangiomas, nine with involuting lesions), five children with vascular malformations, and 25 healthy children study group. Vascular endothelial growth factor and basic fibroblastic growth factor serum levels were analyzed by an ELISA assay. The serum vascular endothelial growth factor concentrations in children with proliferating hemangiomas were significantly higher than in patients with involuting hemangiomas, vascular malformations and healthy patients. The serum basic fibroblastic growth factor concentrations were low and similar in all patients with no statistical correlation between study groups. We concluded that (i) ELISA can easily determine vascular endothelial growth factor concentrations in different phases of hemangioma growth and help distinguishing them from vascular malformations. (ii) A potential role for vascular endothelial growth factor in the pathophysiology of hemangiomas is probable.

Soluble receptors for vascular endothelial growth factor (sVEGFR1/sVEGFR2) in infantile hemangioma

Vascular endothelial growth factor (VEGF) and its receptors were postulated to be involved in pathogenesis of infantile hemangioma. The aim of this study was to determine the serum levels of VEGF and soluble VEGF receptors (sVEGFR1/sVEGFR2) in children with hemangiomas. Materials and methods: Thirty-eight children with infantile hemangiomas (25 proliferating, 13 involuting) and 34 healthy children were included in the study. sVEGFR1 and sVEGFR2 serum levels in peripheral blood and in vascular tumors were determined with ELISA test. Results: sVEGFR1 serum levels were slightly lower in hemangioma patients (p = 0.049). No significant differences in sVEGFR2 levels were observed in any study group. VEGF levels did differ significantly, with median level being 364.05 pg/ml in hemangioma patients and 107.40 pg/ml in the control group (p < 0.0001). Conclusions: The obtained results suggest that VEGF is involved in hemangioma angiogenesis but that soluble VEGFRs marginally influence this process. Lower serum levels of sVEGFR1 in hemangioma patients indicate the possible dysregulation between VEGFR1 and VEGFR2 receptors.

Evaluation of potential prognostic value of Bmi-1 gene product and selected markers of proliferation (Ki-67) and apoptosis (p53) in the neuroblastoma group of tumors.

INTRODUCTION Cancer in children is a very important issue in pediatrics. The least satisfactory treatment outcome occurs among patients with clinically advanced neuroblastomas. Despite much research, the biology of this tumor still remains unclear, and new prognostic factors are sought. The Bmi-1 gene product is a currently highly investigated protein which belongs to the Polycomb group (PcG) and has been identified as a regulator of primary neural crest cells. It is believed that Bmi‑1 and N-myc act together and are both involved in the pathogenesis of neuroblastoma. The aim of the study was to assess the potential prognostic value of Bmi-1 protein and its relations with mechanisms of proliferation and apoptosis in the neuroblastoma group of tumors. MATERIAL/METHODS 29 formalin-fixed and paraffin-embedded neuroblastoma tissue sections were examined using mouse monoclonal antibodies anti-Bmi-1, anti-p53 and anti-Ki-67 according to the manufacturers instructions. RESULTS There were found statistically significant correlations between Bmi-1 expression and tumor histology and age of patients. CONCLUSIONS Bmi-1 seems to be a promising marker in the neuroblastoma group of tumors whose expression correlates with widely accepted prognostic parameters. The pattern of BMI-1 expression may indicate that the examined protein is also involved in maturation processes in tumor tissue.

Prognostic significance of MCM 2 and Ki-67 in neuroblastic tumors in children.

INTRODUCTION Neuroblastic tumors can be characterized by three features: spontaneous regression, maturation and aggressive proliferation. The most common and routinely used method of assessing tumor cell proliferation is to determine the Ki-67 index in the tumor tissue. Despite numerous studies, neuroblastoma biology is not fully understood, which makes treatment results unsatisfactory. MCM 2 is a potential prognostic factor in the neuroblastoma group. MATERIAL/METHODS The study is based on retrospective analysis of 35 patients treated for neuroblastic tumors in the Department of Pediatric Surgery and Oncology of the Medical University of Lodz, during the period 2001-2011. The material comprised tissues of 16 tumors excised during the operation and 19 biopsy specimens. Immunohistochemical examinations were performed with immunoperoxidase using mouse monoclonal anti-MCM 2 and anti-Ki-67 antibodies. RESULTS We observed that MCM 2 expression ranged from 2% to 98% and the Ki-67 index ranged from 0 to 95%. There was a statistically significant correlation between expression of MCM 2 and the value of the Ki-67 index and a correlation close to statistical significance between expression of MCM 2 and unfavorable histopathology. There was no statistical relationship between expression of MCM 2 and age over 1 year and N-myc amplification. DISCUSSION The presented research shows that MCM 2 may have prognostic significance in neuroblastic pediatric tumors and as a potential prognostic factor could be the starting point of new individualized therapy.

Is the SIOP-2001 Classification of Renal Tumors of Childhood accurate with regard to prognosis? A problem revisited

Introduction The goal of this study was to analyze morbidity and mortality of Wilms’ tumor based on the revised SIOP-2001 classification. Material and methods Sixty-four patients with unilateral Wilms’ tumor, 33 girls (51.5%) and 31 boys (48.5%), aged 1 to 144 months (mean: 42.8 months) were treated between 1993 and 2009. All patients underwent multimodal therapy according to the SIOP protocols. The follow-up period ranged from 2 to 18 years (mean: 11.6 years). Results Thirty-three patients (51.6%) had intermediate-risk, 6 (9.4%) low-risk and 25 (39%) high-risk tumors. Stage I disease was diagnosed in 28 (43.7%), stage II in 19 (29.7%), stage III in 8 (12.5%) and stage IV in 9 patients (14.1%). Event-free survival (EFS) in the entire group was 78.1% and OS was 92.2%. The EFS in stage IV (44.4%) was significantly lower than in stage I (82.1%, p = 0.04), stage II (89.5%, p = 0.02) and in the entire group (78.1%, p = 0.04). Sixteen complications were observed in 14 children (21.9%); metastases in 7 cases (10.9%), 8 relapses (12.5%) and 5 deaths (7.8%). Blastemal (20/24 – 83.3%) and anaplastic (3/24 – 12.5%) subtypes were responsible for mortality in high-risk tumors (OS – 87.5%), while poorly differentiated epithelial (7/34 – 20.6%) and regressive (8/34 – 23.5%) subtypes decreased OS (94.1%) in the intermediate-risk tumors. Conclusions The results of our study show that epithelial and regressive subtypes were responsible for mortality in the intermediate-risk Wilms’ tumors.