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

Microbiome impact on metabolism and function of sex, thyroid, growth and parathyroid hormones

Commensal bacteria and their genes associated with host are known as microbiome. In recent years, microbial influence on host endocrine system has been under detailed investigation. The role of microbiome in the pathogenesis of insulin resistance and obesity, the function of hypothalamic-pituitary-adrenal axis and secretion of hormones regulating appetite is well described in world literature. In this article we discuss poorly reviewed issues: the microbiome role in modulation of non-peptide (sex and thyroid) and peptide (growth hormone and parathyroid hormone) functions. Understanding complex bidirectional relations between host endocrine system and bacteria is of fundamental importance to understanding microbial impact on host reproduction, risk of endocrine-related cancers, pathogenesis of non-thyroidal illness syndrome, growth failure in children and hormonal changes during chronic kidney disease. This article also highlights effects of dietary compounds on microbiome composition and bacterial enzymes activity, and thus host hormonal status

Loss of E-Cadherin Staining Continuity in the Trophoblastic Basal Membrane Correlates with Increased Resistance in Uterine Arteries and Proteinuria in Patients with Pregnancy-Induced Hypertension

Pregnancy-induced hypertension (PIH), especially when complicated with pre-eclampsia (PE), could be a life-threatening complication of pregnancy. Pre-eclampsia is one of the leading causes of perinatal morbidity and mortality in women. Pre-eclampsia is mainly characterized by hypertension and kidney damage with proteinuria. Abnormal placentation and altered structure of the placental barrier are believed to participate in the pathogenesis of pregnancy-induced hypertension, leading to PE. In the current study, we aimed to analyze the immunohistochemical expression pattern of E-cadherin and p120, two markers of epithelial–mesenchymal transition, in placental samples derived from a group of 55 patients with pregnancy-induced hypertension, including pre-eclampsia and 37 healthy pregnant controls. The results were correlated with the presence of an obtained early uterine artery flow notching during diastole on Doppler ultrasound. We observed a higher frequency of discontinuous E-cadherin staining in the basement membrane of syncytiotrophoblast in patients with PIH/PE compared to controls (p p p = 0.013, Fisher’s exact test). These findings suggest that E-cadherin contributes to the integrity of the placental barrier, and its loss could be an immunohistochemical marker of PE

Testicular teratoma with nephroblastoma in an adult – case report and literature review

Testicular germ cell tumours are the most common malignancies in young men. Germ cell tumours can be classified as seminomas or non-seminomas, each with different clinical features and treatment approaches. Germ cell tumours are occasionally associated with somatic-type malignancy, particularly in metastatic lymph nodes after adjuvant chemotherapy. Adenocarcinomas and rhabdomyosarcoma are the most common malignancies in this setting. In this report, we present a unique case of a 37-year-old patient who presented with a testicular teratoma containing a nephroblastoma component. The tumour exhibited characteristic morphology that resembled foetal kidney and expressed nuclear WT-1 and PAX-8 on immunohistochemistry. Following surgery, the patient opted for active surveillance and remains disease-free. To date, only 7 cases of nephroblastoma in primary testicular teratoma have been reported. This case highlights the importance of considering this rare entity in the differential diagnosis of testicular teratomas and the need for careful pathological examination

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