ABSTRACT
The accurate evaluation of human epidermal growth factor receptor 2 (HER2) status is essential for the appropriate use of targeted therapies. An increased number of chromosome 17 centromere enumeration probe (CEP17) signals may underrate fluorescence in situ hybridization (FISH) outcomes, resulting in false-negative or a false-equivocal HER2 status assessment. The aim of the present study was to assess the frequency of CEP17 copy number increase (CNI), its effects on HER2 protein expression (and the subsequent effects on tumor cells), and the survival outcomes of patients with gastric cancer. Archival primary tumor samples from 244 patients that underwent gastric resection for adenocarcinoma were retrieved for both HER2 protein expression analysis (using immunochemistry) and HER2 gene amplification (using FISH). The associations between HER2 status, CEP17 CNI and multiple clinicopathological parameters (including survival outcome), were assessed. The relationship between CEP17 CNI and HER2 protein upregulation was also investigated. CEP17 CNI was detected in 17.2% of cases, and a strong association between CEP17 CNI and HER2 upregulation was revealed. The impact of CEP17 CNI on survival did not reach statistical significance. Consequently, CEP17 CNI was discovered to be strongly associated with HER2 upregulation in tumor cells, which may characterize a critical issue in HER2 testing. Therefore, the eligibility for HER2-targeted agents in CEP17 CNI-positive patients warrants further recognition.
ABSTRACT
INTRODUCTION: Tumour angiogenesis is one of the most important hallmarks of cancer, which enables its development, progression and metastasizing. The extent of angiogenesis seems to be an essential prognostic factor in many solid tumours of children and adults. There have also been reports on the significance of angiogenesis in osteosarcoma. The most common methods to estimate angiogenesis is assessment of microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression. AIM: The aim of the study was assessment of angiogenesis in osteosarcoma patients treated in our centre on the basis of MVD and VEGF expression. PATIENTS AND METHODS: Histopathological specimens of 16 patients with osteosarcoma aged 9-18 years (median 13.5), treated in Department of Paediatrics, Paediatric Gastroenterology and Paediatric Oncology of Medical University in Gdansk, between 1997-2004, were studied retrospectively. Immunochemistry was performed using anti CD34 monoclonal antibody and chromogen to highlight vessels, which were counted at 200 x magnification on 3 microscopic fields. In the same specimens VEGF expression was evaluated semiquantitatively using immunohistochemical method. Patients were divided into two groups depending on presence of metastases. The two parameters were also compared in patients who died and the survivors. RESULTS: 11 of 16 patients are alive, with time of follow up 19-100 months (median 52). Five children died. Mean vascular density ranged from 25 to 87 (46 +/- 16.5). No significant statistical difference in microvessel density between metastatic and non-metastatic patients was observed. Microvessel density in these groups is 46.8 +/- 22.7 and 45.2 +/-7.0 respectively. In the group of survivors MVD was 44.3 +/- 5.9, inpatients who died it was 47.1 +/- 21.0 showing no significant statistical difference. In all patients positive VEGF expression was seen. Only one patient presented low expression of VEGF, the rest had high or medium degree of VEGF expression. MVD in the group with high expression of VEGF was higher than in the group with low and medium expression of VEGF. It was 51.8 +/- 18.7 and 39.2 +/- 14.2. The difference was not significant. CONCLUSIONS: In the presented group of patients no differences in the extent of angiogenesis were seen in relation to treatment outcome or presence of metastases.
