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CHL1 and NrCAM are primarily expressed in low grade pediatric neuroblastoma

  • Robin Wachowiak EMAIL logo , Steffi Mayer , Anne Suttkus , Illya Martynov , Martin Lacher , Nathaniel Melling , Jakob R. Izbicki and Michael Tachezy
Published/Copyright: December 31, 2019
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Open Medicine
From the journal Open Medicine Volume 14 Issue 1

Abstract

Background

Neural cell adhesion molecules like close homolog of L1 protein (CHL1) and neuronal glia related cell adhesion molecule (NrCAM) play an important role in development and regeneration of the central nervous system. However, they are also associated with cancerogenesis and progression in adult malignancies, thus gain increasing importance in cancer research. We therefore studied the expression of CHL1 and NrCAM according to the course of disease in children with neuroblastoma.

Methods

CHL1 and NrCAM expression levels were histologically assessed by tissue microarrays from surgically resected neuroblastoma specimens of 56 children. Expression of both markers was correlated to demographics as well as clinical data including metastatic dissemination and survival.

Results

CHL1 was expressed in 9% and NrCAM in 51% of neuroblastoma tissue samples. Expression of CHL1 was higher in patients with low Hughes grade 1a/b (p=0.01). NrCAM was more often detected in patients with a low International Staging System (INSS) score 1/2 (p=0.04).

Conclusion

CHL1 and NrCAM expression was associated with low-grade pediatric neuroblastoma. These adhesion molecules may play a role in early tumor development of neuroblastoma.

Keywords: CHL1; NrCAM; Neuroblastoma; Immunohistochemistry; Tumor markers; Neuropathology

1 Introduction

Neuroblastoma is an embryonic malignancy deriving from neural crest cells that undergo rapid differentiation during fetal development. As the transition from normal to malignant tissue can occur in multiple steps, its phenotype is highly heterogeneous [1]. Although progress has been made in the treatment of neuroblastoma, the outcome of children at high risk remains poor with a long-term survival as low as 50 % [2]. Different parameters such as age, stage and chromosomal aberrations have an impact on prognosis. Still, there is an ongoing need for tumor markers, which allow a better determination of the individual prognosis and therapeutic monitoring especially in high risk patients.

Recently, cell adhesion molecules (CAMs) have been implicated in the processes of malignant transformation and progression [3]. In particular, members of the immunoglobulin superfamily L1, including transmembrane proteins L1CAM, close homologue of L1 (CHL1), neuron glia related CAM (NrCAM) and neurofascin have been identified as important factors [4, 5]. Various studies emphasized the importance of L1CAMs in neuronal migration and survival, axon outgrowth, synaptic plasticity, and regeneration, resulting in a regular development and homoeostasis of the central nervous system (CNS) [6]. Alterations in the expression and function of CAMs, especially L1, CHL1 and NrCAM, have been associated with pathological processes leading to different malignancies including melanoma, prostate and colon cancer [7, 8, 9, 10, 11, 12]. CHL1 can be down- or upregulated in human cancer genesis [13]. An increased expression of NrCAM has been correlated to metastatic development and tumorigenesis in different human cancers [7, 14, 15]. Moreover, overexpression of NrCAM elevates cancer cell motility and invasiveness in vitro and has been linked to a poor prognosis in adult patients [7, 14]. Likewise, overexpression of L1 in adults correlates to tumor progression and metastatic dissemination in glioma, melanoma, ovarial and colon carcinomas [12]. In contrast, an increased expression of NrCAM and L1 in gene array analyses has been associated with a favorable outcome in pediatric neuroblastoma [16, 17].

Taken together, members of the immunoglobulin superfamily L1, which share a similar structure with a 35-45% homology, might serve as interesting prognostic markers in neuroblastoma. The aim of the study was to investigate members of the L1 family with regards to their diagnostic and prognostic potential in this pediatric tumor. We therefore determined the expression of CHL1 and NrCAM by immunohistochemistry in a neuroblastoma tissue microarray and correlated it to the individual course of disease.

2 Material and Methods

2.1 Study design

The study was approved by the Ethics Committee of the Chamber of Physicians in Hamburg, Germany. The research related to human has been complied with all relevant national regulations, institutional policies and in accordance to the tenets of the Helsinki Declaration. Written informed consent was obtained from all parents for investigation of resected neuroblastoma tissue samples. Pediatric patients who underwent surgical treatment of neuroblastoma at the University Medical Center Hamburg Eppendorf between November 1999 and October 2004 were included. No preselection was performed and none of the children was pretreated. Clinical and pathological data included the International Neuroblastoma Staging System (INSS), histological grade (according to Hughes), N-myc amplification, loss of heterozygosity of chromosome 1p (LOH 1p), age at diagnosis, sex, metastatic dissemination and event free as well as overall survival.

2.2 Tissue Microarray

Pediatric neuroblastoma tissues were fixed in 4% buffered formalin and embedded in paraffin as described previously [18]. Hematoxylin-eosin stained sections were cut from primary tumor blocks, containing representative tumor regions. Afterwards, tissue cylinders with a diameter of 600 μm were used to stamp out selected sections of the original donor block. These were arrayed on a new paraffin block using a semi-automated tissue arrayer. Subsequently, 5 μm slides of the complete tissue microarray (TMA) were cut using the paraffin sectioning aid system (Instrumentics, Hackensack, NJ, USA).

2.3 Immunohistochemistry

For immunohistochemistry, 5-μm sections were placed on precoated slides (3-triethoxysilylpropylamin; Merck, Darmstadt, Germany), deparaffinized and exposed to heat-induced antigen retrieval for 5 minutes in an autoclave at 121°C in Tris-EDTA-Citrate buffer, pH 7.8. Afterwards, the primary antibody either specific for CHL1 (goat, polyclonal antibody: AF2126, R&D Systems, MN, USA) or NrCAM (goat anti-human NrCAM antibody: AF2034, R&D Systems, MN, USA,) was applied at 37°C and pH 9.1 for 60 minutes. Bound antibodies were then visualized using the EnVision Kit (Dako, Glostrup, Denmark) according to the manufacturer’s directions. Unaffected pancreatic tissue served as positive and lymphoid as negative controls.

2.4 Quantification of staining intensities

Staining intensities of positive tumor cells were assessed as described recently [19]. In brief, lack of staining was defined negative, while weak, moderate and strong staining were defined positive. Labeled sections were analyzed by two independent investigators (RW and MT) that were blinded to the patient’s identity or clinical status. A pathologist was involved in cases of discrepancy to reach a consensus.

2.5 Statistical Analysis

Statistical analysis was performed by SPSS for Windows version 11.5 (SPSS, IBM Corporation, NY, USA) and Graph-Pad Prism (Version 7.04, GraphPad Software, Inc., San Diego, CA, USA). Chi square test was used to compare categorical variables, Fischer’s exact test to compare odds between two groups and Kruskal-Wallis test for comparisons of continuous variables. Categorical variables are expressed as frequency and percentage; continuous variables are represented as medians with maximum and minimum or as means with standard deviation. Kaplan-Meier survival curves were analyzed using the log-rank test. Significance level was set as p<0.05.

3 Results

3.1 Study population

A total of 56 children (24 female and 32 male) who underwent surgical resection of neuroblastoma were included in the study. Median age at the time of diagnosis was 30 months. The tumor was localized adrenally in 34 (61%) and non-adrenally in 22 (39%) patients. 28 patients (50%) had metastatic dissemination at the time of operation. Median follow-up of all patients was 72 months. During the observation period, six children (11%) died due to the underlying disease.

3.2 Expression of CHL1

Immunohistochemistry revealed a heterogonous staining pattern of CHL1 inside cancerous lesions with predominant membranous expression. Expression of CHL1 was detected in five (9%) samples (Fig. 1A /1B). Each CHL1 positive tumor was classified Hughes grade 1, which differed significantly from CHL1 negative samples (p=0.01). In CHL1 negative samples, Hughes grade 1 (n=17; 33%), 2 (n=15; 29%) and 3 (n=19; 37%) were equally distributed (p>0.05). Comparing CHL1 positive and negative tumor samples, no significant differences regarding INSS stages, n-MYC amplification as well as 1p mutation status were found. Overall (84.2 vs. 69.0 months) and event free (84.3 months vs. 64.0 months) survival of the children did not differ for CHL1 positive and negative samples (Fig. 2 A/B,

Figure 1 Expression of CHL1 and NrCAM in pediatric neuroblastoma. Representative examples of CHL1 positive (A) and CHL-1 negative (B) (magnification x100) as well as NrCAM positive (C) and NrCAM negative (D) immunostaining (magnification x200).
Figure 1

Expression of CHL1 and NrCAM in pediatric neuroblastoma. Representative examples of CHL1 positive (A) and CHL-1 negative (B) (magnification x100) as well as NrCAM positive (C) and NrCAM negative (D) immunostaining (magnification x200).

Figure 2 Kaplan-Meier survival curves for overall and event-free survival. No association was found for CHL1-expression (A/B). Survival rates were better by trend in children with NrCAM positive tumors (C/D) but without statistical significance (p=0.07 and p=0.06).
Figure 2

Kaplan-Meier survival curves for overall and event-free survival. No association was found for CHL1-expression (A/B). Survival rates were better by trend in children with NrCAM positive tumors (C/D) but without statistical significance (p=0.07 and p=0.06).

Tab. 1). Subgroup analysis of overall survival for children with metastatic or non-metastatic tumors as well as adrenally or non-adrenally tumors revealed no statistical difference (data not shown).

Table 1

CHL1 expression as well as clinical, pathologic and molecular characteristics of the analysed neuroblastoma tissue samples. Statistical analyses by using cross-tables, two-sided Fisher´s and Chi-squared test.

Variable Number of patients CHL1 expression p-value
positive negative
Total 56 5 (9%) 51 (91%)
age ≤ 1 year 17 1 (6%) 16 (94%) ns
> 1 year 39 4 (10%) 35 (90%)
sex female 24 (43%) 3 (12%) 21 (88%) ns
male 32 (57%) 2 (6%) 30 (94%)
1 23 (41%) 2 (9%) 21 (91%)
2 13 (23%) 1 (8%) 12 (92%)
INSS 3 7 (13%) 1 (14%) 6 (86%) ns
4 9 (16%) 1 (11%) 8 (89%)
4s 4 (7%) 0 (0%) 4 (100%)
1a/b 22 (39%) 5 (23%) 17 (77%)
Hughes grade 2 15 (27%) 0 (0%) 15 (100%) 0.01
3 19 (34%) 0 (0%) 19 (100%)
n-MYC amplification positive 7 (12%) 0 (0%) 7 (100%)
negative 49 (88%) 5 (10%) 44 (90%) ns
LOH1p detection positive 9 (21%)) 1 (11%) 8 (89%) ns
negative 35 (79%) 2 (6%) 33 (94%)

  1. INSS: International Neuroblastoma Staging System

3.3 Expression of NrCAM

Likewise, a heterogeneous distribution with prevalent membranous staining was observed after immunostaining for NrCAM. 28 (51%) of the samples showed a positive NrCAM expression (Fig. 1C/1D). Patients with NrCAM positive and negative tissue differed significantly in INSS stages (p=0.04). NrCAM positive tumors were pre-dominantly detected in children with earlier INSS stages (stages 1 and 2) as compared to NrCAM negative samples. No significant differences in Hughes grades, n-MYC amplification and 1p mutation could be found (Tab. 2). Overall (76.0 months vs. 65.3 months) and event free (72.6 months vs. 60.0 months) survival rates were better by trend in children with NrCAM positive tumors but without statistical significance (p=0.07 and p=0.06; Fig. 2 C/D). The subgroup analysis revealed a significantly better overall survival for NrCAM positive tumors (73.8 months) compared to NrCAM negative tumors (65.7 months) in children with metastases (p=0.04). Likewise, patients with adrenal tumors had a significantly longer overall survival with NrCAM positive tissue (81.8 months vs. 60.9 months, p= 0.04). The overall survival comparing NrCAM positive and negative tissue of non-adrenal as well as non-metastatic disease revealed no significant differences (data not shown).

Table 2

NrCAM expression as well as clinical, pathologic and molecular characteristics of the analysed neuroblastoma tissue samples. Statistical analyses by using cross-tables, two-sided Fisher´s and Chi-squared test.

Variable Number of patients NrCAM expression p-value
positive negative
Total 55 28 (51%) 27 (49%)
age ≤ 1 year 17 9 (53%) 8 (48%) ns
> 1 year 38 19 (50%) 19 (50%)
sex female 23 (42%) 12 (52%) 11 (48%) ns
male 32 (58%) 16 (50%) 16 (50%)
1 23 (42%) 11 (48%) 12 (52%)
2 12 (22%) 9 (75%) 3 (25%)
INSS 3 7 (13%) 4 (57%) 3 (43%) 0.04
4 9 (16%) 1 (11%) 8 (89%)
4s 4 (7%) 3 (75%) 1 (25%)
1a/b 21 (38%) 10 (48%) 11 (52%)
Hughes grade 2 15 (27%) 11 (73%) 4 (27%) ns
3 19 (35%) 7 (37%) 12 (63%)
n-MYC amplification positive 7 (13%) 2 (29%) 5 (71%) ns
negative 48 (87%) 26 (54%) 22 (46%)
LOH1p detection positive 9 (21%) 4 (44%) 5 (56%) ns
negative 34 (79%) 20 (59%) 14 (41%)

  1. INSS: International Neuroblastoma Staging System

4 Discussion

In the present study, the protein expression of CHL1 and NrCAM in pediatric neuroblastoma in correlation to clinical and survival data were analyzed. CHL1 was spotted in 9% of the patients, each classified as Hughes grade 1a/b. NrCAM was detected in 51% of the cases predominantly in earlier INSS stages 1/2.

Expression of CHL1 as well as NrCAM has already been studied in neuroblastoma before. Lastowska et al. found an overall downregulation of CHL1 in 28 tumor samples that did not impact on the individual prognosis [20]. Conversely, low CHL1 gene expression in 417 neuroblastoma samples was significantly correlated to a reduced overall survival [21]. That parallels our findings of positive protein expression of CHL1 in low tumor grades Hughes 1a/b by immunohistochemistry only. Thus, expression of CHL1 may be associated with high risk, immature neuroblastoma.

Accordingly, an increased NrCAM gene detection has been reported for low risk neuroblastomas with favorable outcome before [17]. In our study, NrCAM protein expression was detected in 51% of patients, predominantly in children with low risk INSS stage 1 and 2. We also found a trend to a better event free and overall survival for children with NrCAM positive tumors [17]. Thus, the tumor may initially still be able to translate and transcribe NrCAM, but loses this ability within progression. Moreover, the survival analysis using subgroups revealed a significantly better overall survival for patients with NrCAM positive tumors in the subgroup of metastatic tumors as well as for patients with adrenal tumors. These results strengthen the findings that children with NrCAM positive tumors have a favorable outcome even if metastases are detected.

Adhesion molecules of the L1 superfamily are typically found in normal neuronal tissue. NrCAM is expressed in the developing as well as adult organism and can be detected in the central as well as peripheral nervous system [22]. It regulates axonal growth and guidance during development. In the mature brain, NrCAM can be detected at the nodes of Ranvier, suggesting a relevant role in synaptic signaling [3, 22]. CHL1 is found in neuronal development regulating axon growth as well as in cell migration in children and to a lesser extent in adult tissue, predominantly during regeneration processes [23]. The downregulation and -expression of CAMs in high grade neuroblastoma tissue may depict the loss of normal function of the originating neuronal tissue. Thus, the expression of CHL1, NrCAM, L1CAM, and ALCAM may be associated with a less aggressive tumor and, as a consequence, with a better prognosis [16, 24, 25]. However, mechanisms of induction, expression, and intracellular signaling of adhesions molecules especially during tumorigenesis have not been understood yet.

The gene expression of NrCAM and CHL1 has also been studied in adult tumors of various entities with a divergent prognosis. CHL1 was down-regulated in colon, stomach, bladder, or pancreatic cancer but upregulated in lung, liver prostate, and cervix cancers [13, 26, 27]. In contrast, higher levels of NrCAM in tumorous tissue deriving from glioblastoma, pancreatic, and colon cancer as well as papillary thyroid carcinoma were associated with a poorer prognosis [14, 15, 28, 29]. These conflictive results for children and adults are in line with previous findings of our group. We found a more favorable outcome for upregulated cell adhesion molecules L1 and ALCAM in pediatric neuroblastoma patients, while higher expression in adult cancer patients was correlated to poor survival [16, 24, 30]. This might be due to the different tumor entities in pediatric neuroblastoma versus malignancies in adulthood. Interestingly, no significant association between survival and the expression of L1 and NrCAM in other embryonic tumors like rhabdomyosarcoma and Wilms tumor could be found by others [31, 32]. In contrast, in CNS tumors like astrocytoma as well as ependymoma, overexpression of L1 or NrCAM was correlated with a poor prognosis [33, 34, 35, 36]. Thus, the underlying embryonic or non-embryonic ethiopathogenesis may impede the role of CAMs in tumorigenesis. However, their value as prognostic markers has not been fully understood yet [13].

In conclusion, CHL1 and NrCAM as members of the L1 superfamily may play an important role in early tumor development. However, larger prospective studies are warranted to better understand the role of adhesion molecules in neuroblastoma and other embryonic tumors in children and adolescents.

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Acknowledgements

We acknowledge support from the German Research Foundation (DFG) and Leipzig University within the program of Open Access Publishing.

  1. Conflict of interest: Authors state no conflict of interest.

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Received: 2018-11-07
Accepted: 2019-10-19
Published Online: 2019-12-31

© 2019 Robin Wachowiak et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Articles in the same Issue

  1. Research Article
  2. Prostate Cancer-Specific of DD3-driven oncolytic virus-harboring mK5 gene
  3. Case Report
  4. Pediatric acute paradoxical cerebral embolism with pulmonary embolism caused by extremely small patent foramen ovale
  5. Research Article
  6. Associations between ambient temperature and acute myocardial infarction
  7. Case Report
  8. Discontinuation of imatinib mesylate could improve renal impairment in chronic myeloid leukemia
  9. Research Article
  10. METTL3 promotes the proliferation and mobility of gastric cancer cells
  11. The C677T polymorphism of the methylenetetrahydrofolate reductase gene and susceptibility to late-onset Alzheimer’s disease
  12. microRNA-1236-3p regulates DDP resistance in lung cancer cells
  13. Review Article
  14. The link between thyroid autoimmunity, depression and bipolar disorder
  15. Research Article
  16. Effects of miR-107 on the Chemo-drug sensitivity of breast cancer cells
  17. Analysis of pH dose-dependent growth of sulfate-reducing bacteria
  18. Review Article
  19. Musculoskeletal clinical and imaging manifestations in inflammatory bowel diseases
  20. Research Article
  21. Regional hyperthermia combined with chemotherapy in advanced gastric cancer
  22. Analysis of hormone receptor status in primary and recurrent breast cancer via data mining pathology reports
  23. Morphological and isokinetic strength differences: bilateral and ipsilateral variation by different sport activity
  24. The reliability of adjusting stepped care based on FeNO monitoring for patients with chronic persistent asthma
  25. Comparison of the clinical outcomes of two physiological ischemic training methods in patients with coronary heart disease
  26. Analysis of ticagrelor’s cardio-protective effects on patients with ST-segment elevation acute coronary syndrome accompanied with diabetes
  27. Computed tomography findings in patients with Samter’s Triad: an observational study
  28. Case Report
  29. A spinal subdural hematoma induced by guidewire-based lumbar drainage in a patient with ruptured intracranial aneurysms
  30. Research Article
  31. High expression B3GAT3 is related with poor prognosis of liver cancer
  32. Effects of light touch on balance in patients with stroke
  33. Oncoprotein LAMTOR5 activates GLUT1 via upregulating NF-κB in liver cancer
  34. Effects of budesonide combined with noninvasive ventilation on PCT, sTREM-1, chest lung compliance, humoral immune function and quality of life in patients with AECOPD complicated with type II respiratory failure
  35. Prognostic significance of lymph node ratio in ovarian cancer
  36. Case Report
  37. Brainstem anaesthesia after retrobulbar block
  38. Review Article
  39. Treating infertility: current affairs of cross-border reproductive care
  40. Research Article
  41. Serum inflammatory cytokines comparison in gastric cancer therapy
  42. Behavioural and psychological symptoms in neurocognitive disorders: Specific patterns in dementia subtypes
  43. MRI and bone scintigraphy for breast cancer bone metastase: a meta-analysis
  44. Comparative study of back propagation artificial neural networks and logistic regression model in predicting poor prognosis after acute ischemic stroke
  45. Analysis of the factors affecting the prognosis of glioma patients
  46. Compare fuhrman nuclear and chromophobe tumor grade on chromophobe RCC
  47. Case Report
  48. Signet ring B cell lymphoma: A potential diagnostic pitfall
  49. Research Article
  50. Subparaneural injection in popliteal sciatic nerve blocks evaluated by MRI
  51. Loneliness in the context of quality of life of nursing home residents
  52. Biological characteristics of cervical precancerous cell proliferation
  53. Effects of Rehabilitation in Bankart Lesion in Non-athletes: A report of three cases
  54. Management of complications of first instance of hepatic trauma in a liver surgery unit: Portal vein ligation as a conservative therapeutic strategy
  55. Matrix metalloproteinase 2 knockdown suppresses the proliferation of HepG2 and Huh7 cells and enhances the cisplatin effect
  56. Comparison of laparoscopy and open radical nephrectomy of renal cell cancer
  57. Case Report
  58. A severe complication of myocardial dysfunction post radiofrequency ablation treatment of huge hepatic hemangioma: a case report and literature review
  59. Solar urticaria, a disease with many dark sides: is omalizumab the right therapeutic response? Reflections from a clinical case report
  60. Research Article
  61. Binge eating disorder and related features in bariatric surgery candidates
  62. Propofol versus 4-hydroxybutyric acid in pediatric cardiac catheterizations
  63. Nasointestinal tube in mechanical ventilation patients is more advantageous
  64. The change of endotracheal tube cuff pressure during laparoscopic surgery
  65. Correlation between iPTH levels on the first postoperative day after total thyroidectomy and permanent hypoparathyroidism: our experience
  66. Case Report
  67. Primary angiosarcoma of the kidney: case report and comprehensive literature review
  68. Research Article
  69. miR-107 enhances the sensitivity of breast cancer cells to paclitaxel
  70. Incidental findings in dental radiology are concerning for family doctors
  71. Suffering from cerebral small vessel disease with and without metabolic syndrome
  72. A meta-analysis of robot assisted laparoscopic radical prostatectomy versus laparoscopic radical prostatectomy
  73. Indications and outcomes of splenectomy for hematological disorders
  74. Expression of CENPE and its prognostic role in non-small cell lung cancer
  75. Barbed suture and gastrointestinal surgery. A retrospective analysis
  76. Using post transplant 1 week Tc-99m DTPA renal scan as another method for predicting renal graft failure
  77. The pseudogene PTTG3P promotes cell migration and invasion in esophageal squamous cell carcinoma
  78. Lymph node ratio versus TNM system as prognostic factor in colorectal cancer staging. A single Center experience
  79. Review Article
  80. Minimally invasive pilonidal sinus treatment: A narrative review
  81. Research Article
  82. Anatomical workspace study of Endonasal Endoscopic Transsphenoidal Approach
  83. Hounsfield Units on Lumbar Computed Tomography for Predicting Regional Bone Mineral Density
  84. Communication
  85. Aspirin, a potential GLUT1 inhibitor in a vascular endothelial cell line
  86. Research Article
  87. Osteopontin and fatty acid binding protein in ifosfamide-treated rats
  88. Familial polyposis coli: the management of desmoid tumor bleeding
  89. microRNA-27a-3p down-regulation inhibits malignant biological behaviors of ovarian cancer by targeting BTG1
  90. PYCR1 is associated with papillary renal cell carcinoma progression
  91. Prediction of recurrence-associated death from localized prostate cancer with a charlson comorbidity index–reinforced machine learning model
  92. Colorectal cancer in the elderly patient: the role of neo-adjuvant therapy
  93. Association between MTHFR genetic polymorphism and Parkinson’s disease susceptibility: a meta-analysis
  94. Metformin can alleviate the symptom of patient with diabetic nephropathy through reducing the serum level of Hcy and IL-33
  95. Case Report
  96. Severe craniofacial trauma after multiple pistol shots
  97. Research Article
  98. Echocardiography evaluation of left ventricular diastolic function in elderly women with metabolic syndrome
  99. Tailored surgery in inguinal hernia repair. The role of subarachnoid anesthesia: a retrospective study
  100. The factors affecting early death in newly diagnosed APL patients
  101. Review Article
  102. Oncological outcomes and quality of life after rectal cancer surgery
  103. Research Article
  104. MiR-638 repressed vascular smooth muscle cell glycolysis by targeting LDHA
  105. microRNA-16 via Twist1 inhibits EMT induced by PM2.5 exposure in human hepatocellular carcinoma
  106. Analyzing the semantic space of the Hippocratic Oath
  107. Fournier’s gangrene and intravenous drug abuse: an unusual case report and review of the literature
  108. Evaluation of surgical site infection in mini-invasive urological surgery
  109. Dihydromyricetin attenuates inflammation through TLR4/NF-kappaB pathway
  110. Clinico-pathological features of colon cancer patients undergoing emergency surgery: a comparison between elderly and non-elderly patients
  111. Case Report
  112. Appendix bleeding with painless bloody diarrhea: A case report and literature review
  113. Research Article
  114. Protective effects of specneuzhenide on renal injury in rats with diabetic nephropathy
  115. PBF, a proto-oncogene in esophageal carcinoma
  116. Use of rituximab in NHL malt type pregnant in I° trimester for two times
  117. Cancer- and non-cancer related chronic pain: from the physiopathological basics to management
  118. Case report
  119. Non-surgical removal of dens invaginatus in maxillary lateral incisor using CBCT: Two-year follow-up case report
  120. Research Article
  121. Risk factors and drug resistance of the MDR Acinetobacter baumannii in pneumonia patients in ICU
  122. Accuracy of tumor perfusion assessment in Rat C6 gliomas model with USPIO
  123. Lemann Index for Assessment of Crohn’s Disease: Correlation with the Quality of Life, Endoscopic Disease activity, Magnetic Resonance Index of Activity and C- Reactive Protein
  124. Case report
  125. Münchausen syndrome as an unusual cause of pseudo-resistant hypertension: a case report
  126. Research Article
  127. Renal artery embolization before radical nephrectomy for complex renal tumour: which are the true advantages?
  128. Prognostic significance of CD276 in non-small cell lung cancer
  129. Potential drug-drug interactions in acute ischemic stroke patients at the Neurological Intensive Care Unit
  130. Effect of vitamin D3 on lung damage induced by cigarette smoke in mice
  131. CircRNA-UCK2 increased TET1 inhibits proliferation and invasion of prostate cancer cells via sponge miRNA-767-5p
  132. Case report
  133. Partial hydatidiform mole and coexistent live fetus: a case report and review of the literature
  134. Research Article
  135. Effect of NGR1 on the atopic dermatitis model and its mechanisms
  136. Clinical features of infertile men carrying a chromosome 9 translocation
  137. Review Article
  138. Expression and role of microRNA-663b in childhood acute lymphocytic leukemia and its mechanism
  139. Case Report
  140. Mature cystic teratoma of the pancreas: A rare cystic neoplasm
  141. Research Article
  142. Application of exercised-based pre-rehabilitation in perioperative period of patients with gastric cancer
  143. Case Report
  144. Predictive factors of intestinal necrosis in acute mesenteric ischemia
  145. Research Article
  146. Application of exercised-based pre-rehabilitation in perioperative period of patients with gastric cancer
  147. Effects of dexmedetomidine on the RhoA /ROCK/ Nox4 signaling pathway in renal fibrosis of diabetic rats
  148. MicroRNA-181a-5p regulates inflammatory response of macrophages in sepsis
  149. Intraventricular pressure in non-communicating hydrocephalus patients before endoscopic third ventriculostomy
  150. CyclinD1 is a new target gene of tumor suppressor miR-520e in breast cancer
  151. CHL1 and NrCAM are primarily expressed in low grade pediatric neuroblastoma
  152. Epidemiological characteristics of postoperative sepsis
  153. Association between unstable angina and CXCL17: a new potential biomarker
  154. Cardiac strains as a tool for optimization of cardiac resynchronization therapy in non-responders: a pilot study
  155. Case Report
  156. Resuscitation following a bupivacaine injection for a cervical paravertebral block
  157. Research Article
  158. CGF treatment of leg ulcers: A randomized controlled trial
  159. Surgical versus sequential hybrid treatment of carotid body tumors
https://doi.org/10.1515/med-2019-0109
Keywords for this article
CHL1; NrCAM; Neuroblastoma; Immunohistochemistry; Tumor markers; Neuropathology
Creative Commons
BY-NC-ND 4.0

Articles in the same Issue

  1. Research Article
  2. Prostate Cancer-Specific of DD3-driven oncolytic virus-harboring mK5 gene
  3. Case Report
  4. Pediatric acute paradoxical cerebral embolism with pulmonary embolism caused by extremely small patent foramen ovale
  5. Research Article
  6. Associations between ambient temperature and acute myocardial infarction
  7. Case Report
  8. Discontinuation of imatinib mesylate could improve renal impairment in chronic myeloid leukemia
  9. Research Article
  10. METTL3 promotes the proliferation and mobility of gastric cancer cells
  11. The C677T polymorphism of the methylenetetrahydrofolate reductase gene and susceptibility to late-onset Alzheimer’s disease
  12. microRNA-1236-3p regulates DDP resistance in lung cancer cells
  13. Review Article
  14. The link between thyroid autoimmunity, depression and bipolar disorder
  15. Research Article
  16. Effects of miR-107 on the Chemo-drug sensitivity of breast cancer cells
  17. Analysis of pH dose-dependent growth of sulfate-reducing bacteria
  18. Review Article
  19. Musculoskeletal clinical and imaging manifestations in inflammatory bowel diseases
  20. Research Article
  21. Regional hyperthermia combined with chemotherapy in advanced gastric cancer
  22. Analysis of hormone receptor status in primary and recurrent breast cancer via data mining pathology reports
  23. Morphological and isokinetic strength differences: bilateral and ipsilateral variation by different sport activity
  24. The reliability of adjusting stepped care based on FeNO monitoring for patients with chronic persistent asthma
  25. Comparison of the clinical outcomes of two physiological ischemic training methods in patients with coronary heart disease
  26. Analysis of ticagrelor’s cardio-protective effects on patients with ST-segment elevation acute coronary syndrome accompanied with diabetes
  27. Computed tomography findings in patients with Samter’s Triad: an observational study
  28. Case Report
  29. A spinal subdural hematoma induced by guidewire-based lumbar drainage in a patient with ruptured intracranial aneurysms
  30. Research Article
  31. High expression B3GAT3 is related with poor prognosis of liver cancer
  32. Effects of light touch on balance in patients with stroke
  33. Oncoprotein LAMTOR5 activates GLUT1 via upregulating NF-κB in liver cancer
  34. Effects of budesonide combined with noninvasive ventilation on PCT, sTREM-1, chest lung compliance, humoral immune function and quality of life in patients with AECOPD complicated with type II respiratory failure
  35. Prognostic significance of lymph node ratio in ovarian cancer
  36. Case Report
  37. Brainstem anaesthesia after retrobulbar block
  38. Review Article
  39. Treating infertility: current affairs of cross-border reproductive care
  40. Research Article
  41. Serum inflammatory cytokines comparison in gastric cancer therapy
  42. Behavioural and psychological symptoms in neurocognitive disorders: Specific patterns in dementia subtypes
  43. MRI and bone scintigraphy for breast cancer bone metastase: a meta-analysis
  44. Comparative study of back propagation artificial neural networks and logistic regression model in predicting poor prognosis after acute ischemic stroke
  45. Analysis of the factors affecting the prognosis of glioma patients
  46. Compare fuhrman nuclear and chromophobe tumor grade on chromophobe RCC
  47. Case Report
  48. Signet ring B cell lymphoma: A potential diagnostic pitfall
  49. Research Article
  50. Subparaneural injection in popliteal sciatic nerve blocks evaluated by MRI
  51. Loneliness in the context of quality of life of nursing home residents
  52. Biological characteristics of cervical precancerous cell proliferation
  53. Effects of Rehabilitation in Bankart Lesion in Non-athletes: A report of three cases
  54. Management of complications of first instance of hepatic trauma in a liver surgery unit: Portal vein ligation as a conservative therapeutic strategy
  55. Matrix metalloproteinase 2 knockdown suppresses the proliferation of HepG2 and Huh7 cells and enhances the cisplatin effect
  56. Comparison of laparoscopy and open radical nephrectomy of renal cell cancer
  57. Case Report
  58. A severe complication of myocardial dysfunction post radiofrequency ablation treatment of huge hepatic hemangioma: a case report and literature review
  59. Solar urticaria, a disease with many dark sides: is omalizumab the right therapeutic response? Reflections from a clinical case report
  60. Research Article
  61. Binge eating disorder and related features in bariatric surgery candidates
  62. Propofol versus 4-hydroxybutyric acid in pediatric cardiac catheterizations
  63. Nasointestinal tube in mechanical ventilation patients is more advantageous
  64. The change of endotracheal tube cuff pressure during laparoscopic surgery
  65. Correlation between iPTH levels on the first postoperative day after total thyroidectomy and permanent hypoparathyroidism: our experience
  66. Case Report
  67. Primary angiosarcoma of the kidney: case report and comprehensive literature review
  68. Research Article
  69. miR-107 enhances the sensitivity of breast cancer cells to paclitaxel
  70. Incidental findings in dental radiology are concerning for family doctors
  71. Suffering from cerebral small vessel disease with and without metabolic syndrome
  72. A meta-analysis of robot assisted laparoscopic radical prostatectomy versus laparoscopic radical prostatectomy
  73. Indications and outcomes of splenectomy for hematological disorders
  74. Expression of CENPE and its prognostic role in non-small cell lung cancer
  75. Barbed suture and gastrointestinal surgery. A retrospective analysis
  76. Using post transplant 1 week Tc-99m DTPA renal scan as another method for predicting renal graft failure
  77. The pseudogene PTTG3P promotes cell migration and invasion in esophageal squamous cell carcinoma
  78. Lymph node ratio versus TNM system as prognostic factor in colorectal cancer staging. A single Center experience
  79. Review Article
  80. Minimally invasive pilonidal sinus treatment: A narrative review
  81. Research Article
  82. Anatomical workspace study of Endonasal Endoscopic Transsphenoidal Approach
  83. Hounsfield Units on Lumbar Computed Tomography for Predicting Regional Bone Mineral Density
  84. Communication
  85. Aspirin, a potential GLUT1 inhibitor in a vascular endothelial cell line
  86. Research Article
  87. Osteopontin and fatty acid binding protein in ifosfamide-treated rats
  88. Familial polyposis coli: the management of desmoid tumor bleeding
  89. microRNA-27a-3p down-regulation inhibits malignant biological behaviors of ovarian cancer by targeting BTG1
  90. PYCR1 is associated with papillary renal cell carcinoma progression
  91. Prediction of recurrence-associated death from localized prostate cancer with a charlson comorbidity index–reinforced machine learning model
  92. Colorectal cancer in the elderly patient: the role of neo-adjuvant therapy
  93. Association between MTHFR genetic polymorphism and Parkinson’s disease susceptibility: a meta-analysis
  94. Metformin can alleviate the symptom of patient with diabetic nephropathy through reducing the serum level of Hcy and IL-33
  95. Case Report
  96. Severe craniofacial trauma after multiple pistol shots
  97. Research Article
  98. Echocardiography evaluation of left ventricular diastolic function in elderly women with metabolic syndrome
  99. Tailored surgery in inguinal hernia repair. The role of subarachnoid anesthesia: a retrospective study
  100. The factors affecting early death in newly diagnosed APL patients
  101. Review Article
  102. Oncological outcomes and quality of life after rectal cancer surgery
  103. Research Article
  104. MiR-638 repressed vascular smooth muscle cell glycolysis by targeting LDHA
  105. microRNA-16 via Twist1 inhibits EMT induced by PM2.5 exposure in human hepatocellular carcinoma
  106. Analyzing the semantic space of the Hippocratic Oath
  107. Fournier’s gangrene and intravenous drug abuse: an unusual case report and review of the literature
  108. Evaluation of surgical site infection in mini-invasive urological surgery
  109. Dihydromyricetin attenuates inflammation through TLR4/NF-kappaB pathway
  110. Clinico-pathological features of colon cancer patients undergoing emergency surgery: a comparison between elderly and non-elderly patients
  111. Case Report
  112. Appendix bleeding with painless bloody diarrhea: A case report and literature review
  113. Research Article
  114. Protective effects of specneuzhenide on renal injury in rats with diabetic nephropathy
  115. PBF, a proto-oncogene in esophageal carcinoma
  116. Use of rituximab in NHL malt type pregnant in I° trimester for two times
  117. Cancer- and non-cancer related chronic pain: from the physiopathological basics to management
  118. Case report
  119. Non-surgical removal of dens invaginatus in maxillary lateral incisor using CBCT: Two-year follow-up case report
  120. Research Article
  121. Risk factors and drug resistance of the MDR Acinetobacter baumannii in pneumonia patients in ICU
  122. Accuracy of tumor perfusion assessment in Rat C6 gliomas model with USPIO
  123. Lemann Index for Assessment of Crohn’s Disease: Correlation with the Quality of Life, Endoscopic Disease activity, Magnetic Resonance Index of Activity and C- Reactive Protein
  124. Case report
  125. Münchausen syndrome as an unusual cause of pseudo-resistant hypertension: a case report
  126. Research Article
  127. Renal artery embolization before radical nephrectomy for complex renal tumour: which are the true advantages?
  128. Prognostic significance of CD276 in non-small cell lung cancer
  129. Potential drug-drug interactions in acute ischemic stroke patients at the Neurological Intensive Care Unit
  130. Effect of vitamin D3 on lung damage induced by cigarette smoke in mice
  131. CircRNA-UCK2 increased TET1 inhibits proliferation and invasion of prostate cancer cells via sponge miRNA-767-5p
  132. Case report
  133. Partial hydatidiform mole and coexistent live fetus: a case report and review of the literature
  134. Research Article
  135. Effect of NGR1 on the atopic dermatitis model and its mechanisms
  136. Clinical features of infertile men carrying a chromosome 9 translocation
  137. Review Article
  138. Expression and role of microRNA-663b in childhood acute lymphocytic leukemia and its mechanism
  139. Case Report
  140. Mature cystic teratoma of the pancreas: A rare cystic neoplasm
  141. Research Article
  142. Application of exercised-based pre-rehabilitation in perioperative period of patients with gastric cancer
  143. Case Report
  144. Predictive factors of intestinal necrosis in acute mesenteric ischemia
  145. Research Article
  146. Application of exercised-based pre-rehabilitation in perioperative period of patients with gastric cancer
  147. Effects of dexmedetomidine on the RhoA /ROCK/ Nox4 signaling pathway in renal fibrosis of diabetic rats
  148. MicroRNA-181a-5p regulates inflammatory response of macrophages in sepsis
  149. Intraventricular pressure in non-communicating hydrocephalus patients before endoscopic third ventriculostomy
  150. CyclinD1 is a new target gene of tumor suppressor miR-520e in breast cancer
  151. CHL1 and NrCAM are primarily expressed in low grade pediatric neuroblastoma
  152. Epidemiological characteristics of postoperative sepsis
  153. Association between unstable angina and CXCL17: a new potential biomarker
  154. Cardiac strains as a tool for optimization of cardiac resynchronization therapy in non-responders: a pilot study
  155. Case Report
  156. Resuscitation following a bupivacaine injection for a cervical paravertebral block
  157. Research Article
  158. CGF treatment of leg ulcers: A randomized controlled trial
  159. Surgical versus sequential hybrid treatment of carotid body tumors
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