Tumor expression of survivin, p53, cyclin D1, osteopontin and fibronectin in predicting the response to neo-adjuvant chemotherapy in children with advanced malignant peripheral nerve sheath tumor

Purpose Selected cell-cycle regulators and extracellular matrix proteins were found to play roles in malignant peripheral nerve sheath tumor (MPNST) biology. We aimed to analyze whether initial tumor tissue expressions of survivin, p53, cyclin D1, osteopontin (OPN) and fibronectin (FN) correlate with the response to neo-adjuvant CHT (naCHT) in children with advanced inoperable MPNST. Methods The study included 26 children with MPNST (M/F 14/12, median age 130 months) treated in Polish centers of pediatric oncology between 1992 and 2013. Tissue expression of markers was studied immunohistochemically in the manually performed tissue microarrays and assessed semi-quantitatively as low and high, based on the rate of positive cells and staining intensity. Results Good response to naCHT was noted in 47.6%, while poor-in 52.4% of patients. The response to naCHT was influenced negatively by the presence of neurofibromatosis NF1 and high initial tumor tissue expression of OPN, survivin, p53 and cyclin D1. Patients with high tumor expression of either OPN, survivin or p53 and those with simultaneous high expression of ≥ 3 of the markers, responded significantly worse to naCHT, than patients, in whom expression of ≤ 2 markers were detected at diagnosis. Nearly, 85% of patients expressing ≥ 3 markers, responded poor to CHT; while 87.5% of children, expressing ≤ 2 markers, were good responders. Conclusion The initial tumor tissue expression of OPN, survivin, p53 and cyclin D1 may serve as markers to predict response to naCHT in pediatric advanced MPNST. Future studies in more numerous group of patients are needed to confirm these preliminary results

Fresh approach to Henoch–Schönlein purpura. Comparison of its course and complications in children and adults in the light of the latest reports

Henoch–Schönlein purpura is a disease that belongs to the group of vasculitides. The disease in children is usually mild, but if it occurs in adulthood it can bring many adverse consequences. In mild forms, the major manifestation is skin lesions. The disease may also affect the joints, kidneys, gastrointestinal tract and lungs. The aim of the study is to present the differences in the course and prognosis of Henoch–Schönlein purpura in children and adults, the diversity of aetiological factors of IgA-associated vasculitis as well as clinical implications and diseases concomitant with purpura. Typically, it is believed that viral and bacterial agents induce Henoch–Schönlein purpura. Vaccination is one of the stimuli which can cause IgA-associated vasculitides. The coexistence of Henoch–Schönlein purpura with neoplasms is another interesting issue. The appearance of purpura may indicate a metastasis or recurrence. In adults, the course of Henoch–Schönlein purpura is much more severe – up to 75% of adults who have developed it have gastrointestinal complications. Renal complications occur in up to 87% of adult patients. Pain in the hip joints in the course of Henoch–Schönlein purpura may be a manifestation of necrosis of the femoral head. There are also described cases of complete myocardial infarcts or only its clinical signs. Epididymitis and scrotal oedema are complications of boys and men who have developed purpura. The occurrence of Henoch–Schönlein purpura in males older than 50 is associated with a worse prognosis. Patients with recurrent vasculitis should be carefully evaluated for the presence of a neoplasm.Plamica Henocha–Schönleina to choroba należąca do grupy zapaleń naczyń. U dzieci ma zwykle łagodny przebieg, natomiast jeżeli wystąpi w wieku dorosłym, niesie za sobą wiele niekorzystnych konsekwencji. W lekkich postaciach występują tylko zmiany skórne. Choroba może także dotykać stawów, nerek, przewodu pokarmowego i płuc. Celem pracy jest wskazanie różnic w przebiegu oraz rokowaniu plamicy Henocha–Schönleina u dzieci i dorosłych, różnorodności czynników etiologicznych zapalenia naczyń związanego z IgA, a także implikacji klinicznych oraz chorób współistniejących z plamicą. Typowo uważa się, że czynniki wirusowe i bakteryjne indukują plamicę Henocha–Schönleina. Szczepienie stanowi jeden z bodźców, który może wywołać zapalenie naczyń związane z IgA. Interesujące jest współwystępowanie plamicy z nowotworem. Jej pojawienie się może również zwiastować przerzut lub wznowę. U dorosłych przebieg tej choroby jest znacznie cięższy. Nawet 75% dorosłych, u których wystąpiła plamica, ma powikłania gastroenterologiczne. Implikacje nerkowe dotyczą nawet 87% dorosłych pacjentów. Ból stawów biodrowych w przebiegu choroby może być manifestacją martwicy głowy kości udowej. Opisano przypadki wystąpienia dokonanego zawału serca lub tylko jego wykładników klinicznych. Zapalenie najądrzy, obrzęk moszny to powikłania dotyczące chłopców i mężczyzn, u których pojawiła się plamica. Wystąpienie tego schorzenia po 50. roku życia u mężczyzn wiąże się z gorszym rokowaniem. Pacjenci z nawracającym zapaleniem naczyń powinni zostać szczególnie wnikliwie przebadani w kierunku obecności nowotworu

High Expression of Solute Carrier Family 2 Member 1 (SLC2A1) in Cancer Cells Is an Independent Unfavorable Prognostic Factor in Pediatric Malignant Peripheral Nerve Sheath Tumor

Malignant peripheral nerve sheath tumor (MPNST) in children is a rare mesenchymal malignancy developing predominantly in the setting of neurofibromatosis type 1. The prognosis in advanced MPNST is poor therefore new prognostic markers are highly needed for optimal therapeutic decisions. In many solid tumors, the bidirectional interactions between hypoxia and inflammation in the tumor microenvironment via functions of tumor-associated cells, like neutrophils, lymphocytes and macrophages, have been investigated recently. There is no data whether in MPNST hypoxic microenvironment may translate into systemic inflammation, which is a well-established factor for worse prognosis in cancer patients. Therefore, we investigated the prognostic significance of markers of tumor hypoxia and systemic inflammation in 26 pediatric malignant peripheral nerve sheath tumors (MPNST). Tumor tissue microarrays were stained for hypoxia-inducible factor-1α (HIF1A), solute carrier family 2 member 1 (SLC2A1, also known as glucose transporter 1 (GLUT1)), carbonic anhydrase 9 (CA9), and vascular endothelial growth factor A (VEGFA) and classified into low- or high-expression groups. Baseline complete blood counts and C-reactive protein (CRP) levels were collected for all cases. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were calculated from age-adjusted complete blood count parameters. Both 10-year RFS and OS were significantly lower in patients with high NLR values (17% vs. 75%, p = 0.009, q = 0.018; and 31% vs. 100%, p = 0.0077, q = 0.014; respectively). Ten-year-OS was significantly lower in patients with high expression of SLC2A1 (20.00% vs. 94%, p < 0.001, log-rank), high expression of HIF1A (23% vs. 79%, p = 0.016, log-rank), and CRP higher than 31 mg/L (11% vs. 82%, p = 0.003, q = 0.009). Cox’s proportional hazard regression analysis revealed that high expression of SLC2A1 (HR = 3.31, 95% CI = 1.08–10.09, p = 0.036) and VEGFA (HR = 4.40, 95% CI = 0.95–20.34, p = 0.058) were the independent factors predicting relapse, whereas high SLC2A1 was identified as the independent risk factor for death (HR = 12.20, 95% CI = 2.55–58.33, p = 0.002). Patients with high expression of hypoxic markers and low or high NLR/CRP values had the highest events rate, patients with low hypoxic markers and high NLR/CRP had intermediate events rate, while patients with low hypoxic markers and low NLR/CRP had the lowest events rate. SLC2A1 and VEGFA are promising novel prognostic factors in pediatric MPNST. Correlations between hypoxic and systemic inflammatory markers suggest the interplay between local tumor hypoxia and systemic inflammation