Factors affecting the variable outcomes of juvenile nasopharyngeal angiofibroma (2012)

Background Juvenile Nasopharyngeal Angiofibroma (JNA) is a rare, benign tumour affecting adolescent males. Due to its capability to erode bone, JNA can be accompanied by life-threatening complications when growing into the cranium. The etiology of JNA is unknown, as are the factors determing the variable growth patterns of individual tumours. The treatment of choice for JNA is surgery, but high recurrence rates or persistent growth are charasteristic. \n\nAims The aim of this study was to elucidate factors determing the variable outcomes of JNA. For this purpose the various surgical techniques used to resect JNA during the past 40 years at the Helsinki University Central Hospital (HUCH) were investigated, immunohistochemistry was performed and the gene copy number and mRNA expression data of two phenotypically different JNA tumours were combined to seek for processes putatively determining their growth pattern. \n\nMethods Retrospective clinicopathological data of all JNA patients diagnosed and treated, during the years 1970-2011, were reviewed. By immunohistochemistry, we investigated the cellular distribution and expression levels of C-KIT, C-MYC, BMI-1, GLUT-1, tenascin-C, syndecan-1, syndecan-2 and SYK in JNA samples, in order to find their possible correlations with clinicopathological factors. Comparative genomic hybridisation and gene expression analyses were performed for two phenotypically different tumour samples to investigate the possible processes leading to more aggressive growth. A gene ontology enrichment analysis for the in silico translated proteins of genes with altered gene expression status was performed to detect the categories with enrichments. \n\nResults The primary recurrence rate was 37% and correlated with the surgical approach used, transpalatal approach linked with higher risk of recurrence, vascularity of the tumour and young age of the patient. Contrary to previous reports, C-KIT was expressed in both stromal and endothelial cells of JNA samples and was more prominent in slit-like vessels. A correlation between its endothelial expression and cellular density of the tumour was found. Frequent stromal tenascin-C expression had a strong correlation with vessel density and higher tumour stage. When present, endothelial GLUT-1 expression correlated with higher tumour stage. SYK expression was found to correlate with lower tumour stage. Between the low and high stage JNA tumours studied, 1245 genes showed at least a two-fold- change in their expression. The corresponding proteins of these transcripts were enriched in different biological processes, e.g., hypoxia in the low stage tumour and signal transduction activity in the high stage tumour. \n\nConclusions The type of surgical approach seemed crucial for the outcome. Other clinical factors affecting the recurrence rate were young age of the patient and vascular density of the tumour. In selective cases of JNA, we could thus carefully recommend the consideration of antiangiogenic treatment. Based on our finding of protein expressions, we suggest that at least C-KIT, tenascin-C, GLUT-1 and SYK might be substantial in the growth of JNA by having an effect on tumour cellularity, vessel density and the stage of the tumour. Based on our result of GLUT-1 positivity correlating with higher tumour stage, we suggest that JNAs are not likely to be vascular malformations. Although we were able to identify gene expression changes that relate to particular biological processes, the assessing of clinically relevant molecular profiles of JNA still requires further characterization. In the future, combinating molecular profiling data from several studies will be useful to better understand the molecular background of this rare tumour.