A p16 tumorszuppresszor expressziojanak prognosztikai szerepe magyarorszagi szajuregi laphamrakokban.

Beside smoking and alcohol consumption, human papillomavirus (HPV) infection is the most common risk factor of squamous cell carcinoma in the head and neck region (HNSCC). The latter group of patients associates with better prognosis. During HPV infection, the level of p16 tumor suppressor elevates, which could give an additional opportunity for diagnosis: instead of molecular diagnostic tools, the application of immunohistochemistry is acceptable. However, the majority of the published studies focused on the whole head and neck region and did not separately handled cancers of the oral cavity. Our recent work analyzed the expression of p16 in 67 oral squamous cancers, and compared to routine clinicopathologic parameters. From surgical samples tissue microarray blocks were prepared and expression of p16 as well as other molecular markers (p53, Ki67, EGFR) were studied. In contrast to previous studies on HNSCC, with the exception of recurrence, the expression of p16 was not found associated to clinicopathologic parameters. Nuclear stabilization of p53 appeared mainly in younger patients. The expression of p53 and EGFR significantly correlated to each other. We concluded that traditional molecular categorization of HNSCC could not be completely adaptable to Hungarian samples. Potential coexposition of common etiological factors (e.g. HPV, smoking, alcohol) could blur borders between distinct categories

A p16 tumorszuppresszor expressziójának prognosztikai szerepe magyarországi szájüregi laphámrákokban.

A fej-nyaki régió laphámrákjának legfontosabb rizikófaktorai az alkohol- és dohányexpozíció, illetve a humán papillómavírussal (HPV) való fertőzés, mely utóbbi alcsoport jóval kedvezőbb klinikai prognózist mutat. A p16 tumorszuppresszor sejten belüli szintje magas kockázatú HPV-fertőzés mellett megemelkedik, ami lehetőséget teremt arra, hogy molekuláris diagnosztikai módszerek helyett immunhisztokémia segítségével diagnosztizáljuk a fertőző ágens jelenlétét. A témában megjelent legtöbb kutatás a fej-nyaki régió egészére fókuszált, és nem kezelte külön a szájüregi lokalizációt. Munkánk során a szájüregi régióból műtétileg eltávolított 67 rosszindulatú laphámdaganat p16-expresszióját vizsgáltuk, és vetettük össze a fej-nyaki régióban rutinszerűen meghatározott klinikopatológiai paraméterekkel. A műtéti anyagokból tissue microarray (TMA) blokkokat készítettünk, majd immunhisztokémiai vizsgálat segítségével megvizsgáltuk a p16, illetve több más ismert molekuláris marker (p53, Ki67, EGFR) expresszióját. A fej-nyak régió laphámrákjait taglaló szakirodalmi adatokkal ellentétben saját szájüregi anyagunkban nem kaptunk összefüggést a fő klinikai paraméterekkel, a p16-pozitivitás csupán a recidíva tekintetében jelentett kedvező prognózist. A magi p53-pozitivitás főként a fiatalabb betegcsoportra volt jellemző. A p53- és az EGFR-expresszió statisztikailag szignifikáns korrelációt mutatott egymással. Megállapítottuk, hogy a fej-nyaki laphámrákokban alkalmazott molekuláris csoportosítás nem adaptálható teljes egészében a hazai szájüregi laphámrákokra. Felmerül az egyes etiológiai tényezők (HPV, dohányzás, alkohol) ko-expozíciós szerepe, ami megnehezíti az egyes kategóriák elkülönítését

Region Specific Differences of Claudin-5 Expression in Pediatric Intracranial Ependymomas: Potential Prognostic Role in Supratentorial Cases

Ependymomas are common pediatric brain tumors that originate from the ependyma and characterized by poor prognosis due to frequent recurrence. However, the current WHO grading system fails to accurately predict outcome. In a retrospective study, we analyzed 54 intracranial pediatric ependymomas and found a significantly higher overall survival in supratentorial cases when compared to infratentorial tumors. Next we performed region-specific immunohistochemical analysis of the ependyma in neonatal and adult ependyma from the central canal of spinal cord to the choroid plexus of lateral ventricles for components of cell-cell junctions including cadherins, claudins and occludin. We found robust claudin-5 expression in the choroid plexus epithelia but not in other compartments of the ependyma. Ultrastructural studies demonstrated distinct regional differences in cell-cell junction organization. Surprisingly, we found that 9 out of 20 supratentorial but not infratentorial ependymomas expressed high levels of the brain endothelial tight junction component claudin-5 in tumor cells. Importantly, we observed an increased overall survival in claudin-5 expressing supratentorial ependymoma. Our data indicates that claudin-5 expressing ependymomas may follow a distinct course of disease. The assessment of claudin-5 expression in ependymoma has the potential to become a useful prognostic marker in this pediatric malignancy

Evaluation of Histological and non-Invasive Methods for the Detection of Liver Fibrosis: The Values of Histological and Digital Morphometric Analysis, Liver Stiffness Measurement and APRI Score.

Prognosis and treatment of liver diseases mainly depend on the precise evaluation of the fibrosis. Comparisons were made between the results of Metavir fibrosis scores and digital morphometric analyses (DMA), liver stiffness (LS) values and aminotransferase-platelet ratio (APRI) scores, respectively. Liver biopsy specimens stained with Sirius red and analysed by morphometry, LS and APRI measurements were taken from 96 patients with chronic liver diseases (56 cases of viral hepatitis, 22 cases of autoimmune- and 18 of mixed origin). The strongest correlation was observed between Metavir score and DMA (r = 0.75 p < 0.05), followed in decreasing order by LS and Metavir (r = 0.61), LS and DMA (r = 0.47) LS and APRI (r = 0.35) and Metavir and APRI (r = 0.24), respectively. DMA is a helpful additional tool for the histopathological evaluation of fibrosis, even when the sample size is small and especially in case of advanced fibrosis. The non-invasive methods showed good correlation with the histopathological methods; LS proved to be more accurate than APRI. The stronger correlation between LS values and Metavir scores, as well as the results of DMA in case of appropriate sample size were remarkable

Region specific differences of claudin-5 expression in pediatric intracranial ependymomas: Potential prognostic role in supratentorial cases

Ependymomas are common pediatric brain tumors that originate from the ependyma and characterized by poor prognosis due to frequent recurrence. However, the current WHO grading system fails to accurately predict outcome. In a retrospective study, we analyzed 54 intracranial pediatric ependymomas and found a significantly higher overall survival in supratentorial cases when compared to infratentorial tumors. Next we performed region-specific immunohistochemical analysis of the ependyma in neonatal and adult ependyma from the central canal of spinal cord to the choroid plexus of lateral ventricles for components of cell-cell junctions including cadherins, claudins and occludin. We found robust claudin-5 expression in the choroid plexus epithelia but not in other compartments of the ependyma. Ultrastructural studies demonstrated distinct regional differences in cell-cell junction organization. Surprisingly, we found that 9 out of 20 supratentorial but not infratentorial ependymomas expressed high levels of the brain endothelial tight junction component claudin-5 in tumor cells. Importantly, we observed an increased overall survival in claudin-5 expressing supratentorial ependymoma. Our data indicates that claudin-5 expressing ependymomas may follow a distinct course of disease. The assessment of claudin-5 expression in ependymoma has the potential to become a useful prognostic marker in this pediatric malignancy

Angiogenesis and Angiogenic Tyrosine Kinase Receptor Expression in Pediatric Brain Tumors

Tumor angiogenesis and receptor tyrosine kinases (RTK) are major novel targets in anticancer molecular therapy. Accordingly, we characterized the vascular network and the expression pattern of angiogenic RTK in the most frequent pediatric brain tumors. In a retrospective collection of 44 cases (14 astrocytoma, 16 ependymoma and 14 medulloblastoma), immunohistochemistry for VEGFR1, VEGFR2, PDGFRα, PDGFRβ, and c-Kit as well as microvessel labeling with CD34 and SMA were conducted on surgical specimens. We found a significantly higher vascular density in ependymoma. Glomeruloid formations were abundant in medulloblastoma but rare or almost absent in astrocytoma and ependymoma, respectively. C-Kit and VEGFR2 labeled blood vessels were more abundant in ependymoma than in the other two types of tumors. In contrast, medulloblastoma contained higher number of PDGFRα expressing vessels. In tumor cells, we found no VEGFR2 but VEGFR1 expression in all three tumor types. PDGFRα was strongly expressed on the tumor cells in all three malignancies, while PDGFRβ tumor cell expression was present in the majority of medulloblastoma cases. Interestingly, small populations of c-Kit expressing cancer cells were found in a number of medulloblastoma and ependymoma cases. Our study suggests that different angiogenic mechanisms are present in ependymoma and medulloblastoma. Furthermore ependymoma patients may benefit from anti-angiogenic therapies based on the high vascularization as well as the endothelial expression of c-kit and VEGFR2. The expression pattern of the receptors on tumor cells also suggests the targeting of specific angiogenic tyrosine kinase receptors may have direct antitumor activity. Further preclinical and biomarker driven clinical investigations are needed to establish the application of tyrosine kinase inhibitors in the treatment of pediatric brain tumors