The impact of extent of resection in surgical outcome of pilomyxoid astrocytoma: a case study

The pilomyxoid astrocytoma (PMA) is a rare glioma that has recently been identified as a separate entity and is frequently found in the hypothalamic region. PMA is a subtype of pilocytic astrocytoma (PA), with clinical, histological, and molecular data indicating a close relationship as well as more aggressive biological behaviour in the former. There is still doubt in surgical outcome of PMA that the extent of resection, independent of location or age, is a key factor of recurrence and subsequent therapeutic choices. However, further study is needed to better understand its behaviour and, as a result, establish a consensus on its management. This research features a 2-year-6-month-old female who sought medical attention after complaining of weight loss for four weeks and vomiting for two weeks prior to her visit to the doctor. She had no additional symptoms. Only bilateral pailledema was found during the physical examination. The magnetic resonance imaging (MRI) scans revealed a tumor in the sellar area with heterogeneous enhancement. The patient had ventriculoperitoneal (VP) shunting followed by partial tumor excision twice (Extent of resection 35 percent followed by 16 percent as total 51 percent). The histology and immunohistochemical investigations revealed typical PMA characteristics. Adjuvant treatment, which included chemotherapy and radiosurgery, was initiated for the patient. She has been asymptomatic for two years and has showed no indications of progression of the disease on follow-up scans.

Indonesian Genomic Landscape of Pathogenic Mutation of APC, KRAS, TP53, PIK3CA, and MLH1 in Colorectal Cancer

Background : Knowing colorectal cancer’s heterogeneity and dynamic features, recognizing its biological behaviour requires detailed identification of mutated genes involved. Colorectal cancer (CRC) requires several mutated genes to occur and those are dissimilar in each person hence essential to be discovered in specific population. Until recently, there is no known study describing genomic landscape of CRC in Indonesian population. This study aims to describe profile of pathogenic mutation of APC, TP53, PIK3CA, KRAS, and MLH1 in CRC patients treated at 3 different hospitals in Jakarta. Methods : This is a descriptive study conducted on CRC patients who underwent neoadjuvant, surgical, and adjuvant therapy at RSCM, RSKJ, and MRCCC in 2017-2018. DNA analysis was performed using next-generation sequencing and aligned against GRCh38. Pathogenic variant was identified using ACMG classification and FATHMM score. Data related to behaviour and survival were collected from medical records. Results : There were total 22 subjects in which APC, TP53, and PIKCA were mutated. KRAS mutation occurred in 64%, while MLH1 in 45%. Five types of mutation were identified, including nonsense, missense, frameshift, splice-site, and silent mutation. There are 4 groups of co-occurring mutations, which are APC, TP53, PIK3CA (triple mutation/TM) alone; TM+KRAS; TM+MLH1; and TM+KRAS+MLH1, presenting different nature and survival. Conclusion : Indonesia having various ethnicities with diverse diet and lifestyle has distinct profile of pathogenic mutation presenting mostly with locally-advanced stage with various outcome and survival rate.

Effect of Hafnium Coating on Osseointegration of Titanium Implants: A Split Mouth Animal Study

The behaviour of hafnium as surface coating in biological environments has not been studied. Little is known about osseointegration of hafnium-coated titanium implants. Thus, further studies of hafnium coating under biological conditions are required in order to determine the suitability of this material, as a surface coating for biomedical application. The aim of the study is to analyse the difference between hafnium-coated titanium and uncoated titanium by evaluating the osseointegration ability of hafnium metal and mechanism of which promotes better bone integration. The study was conducted with a split mouth design on 16 Wistar Albino rats of both sexes, at the age of 6-7 months, weighing 2526.5 ± 74.4 g . Self-tapping titanium osteosynthesis screws ( 4 mm × 2 mm ) (LeForte System Bone Screw®) were implanted in the mandible of rats: Group A (pure titanium screws, n = 12 ) and Group B (hafnium-coated screws, n = 12 ). The implanted screws’ stability was checked and noted with a specially customised torque apparatus during insertion and removal of implant. The tissue sections were then processed for hematoxylin and eosin and Masson’s trichrome for bone and connective tissue examination, after 4 and 8 weeks of placement. Hafnium coating appears to have offered similar biocompatibility (aspartate transaminase (AST), alanine aminotransferase (ALT), and creatine kinase (CK) enzyme assay), statistically significant improvement (independent Student’s t -test, p < 0.05 ) in insertion torque ( 25.42 ± 3.965 ) and removal torque ( 29.17 ± 2.887 ) than commercially pure titanium with insertion torque ( 22.08 ± .575 ) and removal torque ( 25.42 ± 2.575 ). Hafnium coating in the rat mandible showed promising osseointegration with good tissue biocompatibility. Further human trials of hafnium-coated implants are needed to understand the biological behaviour better to enhance clinical performance.

Prognostic Value of TRPM7 Expression and Factor XIIIa-Expressing Tumor-Associated Macrophages in Gastric Cancer

Purpose. TRPM7 is known to play a key role in tumor progression by regulating cellular proliferation, migration, and invasion in various cancer cell lines. However, there are no comprehensive clinical studies about the effect of TRPM7 expression on gastric cancer (GC) prognosis. In this study, it was aimed at investigating the effect of TRPM7 expression on prognosis in GC patients. Additionally, for the first time, it was investigated whether the density of Factor XIIIa-expressing tumor-associated macrophages (TAMs) in GC has an effect on the biological behaviour of the tumor. Methods. TRPM7 expression and Factor XIIIa-expressing TAM density were immunohistochemically evaluated in paraffin-embedded tumor tissues of 204 GC patients undergoing surgery at a single institution. Results. Tumor size was clearly higher in cases with high TRPM7 expression than those with low expression ( p < 0.001 , Mann-Whitney U ). TRPM7 overexpression was closely related to high depth of tumor invasion ( p < 0.001 , ANOVA), increased lymph node metastasis ( p < 0.001 , ANOVA), and high distant metastasis rate ( p < 0.001 , Mann-Whitney U ). These findings exposed that high TRPM7 expression is effective in the progression and aggressiveness of GC. In addition, while high CD8+ TIL density affects the prognosis positively, it was determined that high Factor XIIIa+ TAM density negatively affects the prognosis of patients with GC. Furthermore, multivariate analyses revealed TRPM7 overexpression was independently related with short overall (HR 9.64, 95% CI 5.74–16.19, p < 0.001 ) and disease-free survival (HR 5.67, 95% CI 3.61-8.92, p < 0.001 ) in GC patients. Conclusions. Our data suggest that high TRPM7 expression is closely related to progressive tumor behaviour in GC and independently negatively affects survival in patients. In addition, it was determined that a high density of Factor XIIIa+ TAMs negatively affects the prognosis of patients with GC.

Abnormal Methylation of SF-1 Gene Promoter Region in Endometrial Cancer and Its Mechanism

We aim to investigate the methylation status, protein expression and clinical significance of the steroidogenic factor-1(SF-1) in endometrial carcinoma (EC), and explore the effect of abnormal methylation of SF-1 on the biological behaviour of EC. Bisulfite sequencing (BSP), western blotting (WB), and immunohistochemical were used to detect the methylation status and protein expression of SF-1 in EC tissues, paracancerous tissues and normal endometrial tissues. DNA methyltransferase inhibitor 5-Aza-CdR were used to treat HEC-1-A cell lines to demethylate SF-1. After treatment, WB and qPCR were used to detect the expression of SF-1 and its downstream target genes. Cell proliferation and apoptosis were detected by the EdU fluorescent labelling method and flow cytometry between the groups. Compared with paracancerous tissues and normal endometrial tissues, the expression of SF-1 protein in EC tissues was significantly increased (P﹤0.05). The percentage of methylated cytosine in the promoter region of the SF-1 gene in EC tissues (8.2%) was significantly lower than that in paracancerous tissues by 40.9% (P<0.05). Compared with the control group, after 5-Aza-CdR treatment, the methylation level of the SF-1 gene was significantly reduced (P﹤0.05), the expressions of SF-1 and its downstream target genes were significantly increased (P <0.05), the cell proliferation was enhanced and the cell apoptosis was significantly reduced (P <0.05). In conclusion, in EC, SF-1 gene was hypomethylated and the expression of SF-1 was increased, which promotes cell proliferation and inhibits cell apoptosis. SF-1 may become a new molecular target for early diagnosis and treatment in EC.

ETV5-mediated upregulation of lncRNA CTBP1-DT as a ceRNA facilitates HGSOC progression by regulating miR-188-5p/MAP3K3 axis

High-grade serous ovarian cancer (HGSOC) is a common and lethal cancer of the female reproductive system. Long non-coding RNAs (lncRNAs) are aberrantly expressed in various cancers and play crucial roles in tumour progression. However, their function and molecular mechanism in HGSOC remain largely unknown. Based on public databases and bioinformatics analyses, the overexpression of lncRNA CTBP1-DT in HGSOC tissues was detected and validated in a cohort of HGSOC tissues. High expression of lncRNA CTBP1-DT was associated with poor prognosis and was an independent risk factor for survival. Overexpression of lncRNA CTBP1-DT promoted malignant biological behaviour of HGSOC cells, whereas its depletion induced growth arrest of HGSOC cells by vitro and in vivo assays. Mechanistically, lncRNA CTBP1-DT could competitively bind to miR-188-5p to protect MAP3K3 from degradation. Moreover, our results revealed that ETV5 could specifically interact with the promoter of lncRNA CTBP1-DT and activate its transcription. Collectively, these results reveal a novel ETV5/lncRNA CTBP1-DT/miR-188-5p/MAP3K3 pathway for HGSOC progression and suggest that lncRNA CTBP1-DT might be a potential biomarker and therapeutic target for HGSOC.

Hsa_circ_0008434 regulates USP9X expression by sponging miR-6838-5p to promote gastric cancer growth, migration and invasion

Background The role of circular RNAs (circRNAs) in the occurrence and development of gastric cancer (GC) has recently attracted increasing interest. The following study investigates the role of a newly discovered hsa_circ_0008434, which has been confirmed to be highly expressed in GC tissues, in regulating GC biological behaviour. Methods High-throughput RNA sequencing was used to identify differentially expressed genes between normal gastric tissues and GC tissues; actinomycin D and RNase R assays were used to determine the stability and loop structure of hsa_circ_0008434; and the miRanda database was used to predict the target genes of hsa_circ_0008434. The role of hsa_circ_0008434 in cell proliferation, migration, and invasion was examined using CCK-8, wound healing, Transwell and colony formation assays. The regulatory relationships among hsa_circ_0008434, microRNA-6838 (miR-6838), and ubiquitin-specific peptidase 9X (USP9X) were determined by dual-luciferase activity assays. The expression of hsa_circ_0008434 and miR-6838 was measured by qPCR; the expression of USP9X was detected by immunohistochemistry and Western blotting. The effects of hsa_circ_0008434 on in vivo tumour growth were assessed in xenograft models. Results We found that hsa_circ_0008434 was one of the most upregulated circRNAs in GC tissue versus normal tissue. Further in vitro testing indicated that by acting as a miRNA sponge for miR-6838-5p, hsa_circ_0008434 promotes the expression of USP9X and further increases the proliferation, migration, and invasion of GC cells. In addition, animal studies indicated that hsa_circ_0008434 could promote tumour growth in vivo. Conclusions Hsa_circ_0008434 may promote GC proliferation, invasion and migration by regulating the expression of miR-6838 and USP9X.

TERT Promoter Mutations and rs2853669 Polymorphism: Useful Markers for Clinical Outcome Stratification of Patients With Oral Cavity Squamous Cell Carcinoma

ObjectiveTo date, no useful prognostic biomarker exists for patients with oral squamous cell carcinoma (OCSCC), a tumour with uncertain biological behaviour and subsequent unpredictable clinical course. We aim to investigate the prognostic significance of two recurrent somatic mutations (-124 C&gt;T and -146 C&gt;T) within the promoter of telomerase reverse transcriptase (TERT) gene and the impact of TERT single nucleotide polymorphism (SNP) rs2853669 in patients surgically treated for OCSCC.MethodsThe genetic frequencies of rs2853669, -124 C&gt;T and -146 C&gt;T as well as the telomere length were investigated in 144 tumours and 57 normal adjacent mucosal (AM) specimens from OCSCC patients.ResultsForty-five tumours harboured TERT promoter mutations (31.3%), with -124 C&gt;T and -146 C&gt;T accounting for 64.4% and 35.6% of the alterations respectively. Patients with -124 C&gt;T TERT promoter mutated tumours had the shortest telomeres in the AM (p=0.016) and showed higher risk of local recurrence (hazard ratio [HR]:2.75, p=0.0143), death (HR:2.71, p=0.0079) and disease progression (HR:2.71, p=0.0024) with the effect being potentiated by the co-occurrence of T/T genotype of rs2853669.Conclusion-124 C&gt;T TERT promoter mutation as well as the T/T genotype of the rs2853669 SNP are attractive independent prognostic biomarkers in patients surgically treated for OCSCC, with the coexistence of these genetic variants showing a synergistic impact on the aggressiveness of the disease.

Primary leptomeningeal low-grade Schwann cell neoplasm

We discuss an extremely rare case of low-grade Schwann cell leptomeningeal neoplasm with no evident intradural primary, presenting with rapid neurological decline leading to death reflecting the aggressive biological behaviour of this entity despite its low-grade morphology. Notwithstanding extensive investigations, the diagnosis was only established on autopsy as clinical presentation is non-specific making diagnosis challenging. This condition could be considered in patients presenting with leptomeningeal disease if initial workup of more common causes is non-revealing.

Correlation of Clinical, Histopathological and Histomorphometric Features of Canine Soft Tissue Sarcomas

Soft-tissue sarcomas (STS) represent a heterogeneous group of tumours with similar histological characteristics and biological behaviour. This study aimed to describe the correlation between clinical, histopathological and histomorphometric features of STS in dogs. Medical records were reviewed to identify all dogs in which an STS was diagnosed between 2006-2017. Thirty cases were included, and tumour samples and medical records were recovered. Most of the dogs were mixed breed (40%) and 80% of the STS were located in the subcutaneous connective tissue. Histopathological classification showed that undifferentiated sarcoma (17%) and peripheral nerve sheath tumour (30%) were the most common STS. Grade I STS were obtained in 50% of cases (15/30), and grade II or III tumours compromised 43% (13/30) and 7% (2/30) respectively. The mitotic index ranged from zero to 26 (5.8 ± 7.5). Increased nucleus:cytoplasm ratio was moderately associated with higher tumour grade (p = 0.05; rS = 0.361) and mitotic index (p = 0.05; rS = 0.355), while the number of microvessels was positively correlated with degree of differentiation (p = 0.05; rS = 0.362) and nuclear pleomorphism (p = 0.036; rS = 0.384). Histomorphometry proved to be useful in the evaluation of STS, representing an additional tool correlated with well-established prognostic factors (histopathological grade, degree of differentiation, nuclear pleomorphism).