scholarly journals Melanoma: clinical-pathological and molecular analysis in patients of Ibague city, Colombia

Duazary ◽  
2020 ◽  
Vol 17 (1) ◽  
pp. 5-18 ◽  
Author(s):  
Carlos Puentes ◽  
Ana Estrada ◽  
Mabel Bohórquez ◽  
Anggi Vélez ◽  
Carlos Giraldo ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Mitotic Rate ◽  
Clinicopathological Characteristics ◽  
Lower Limbs ◽  
Braf Gene ◽  
Acral Lentiginous Melanoma ◽  
Kaplan Meier ◽  
Age Of Diagnosis ◽  
Pathology Reports ◽  
Clinicopathological Variables

This study aimed to establish the clinicopathological characteristics of patients with melanoma and its association with BRAF gene mutations. The pathology reports and paraffin-embedded tumor samples from 47 women and 30 men with melanoma, with an average age of diagnosis of 60 years, were reviewed at the Hospital Federico Lleras Acosta of Ibague, between 2010 and 2016. The presence of V600E mutation at the exon 15 of BRAF gene, was analyzed in these tumoral samples by Sanger sequencing and visual inspection of the electropherograms. We also studied the clinicopathological variables with X2, t-Student and the Kaplan Meier index. Most of the lesions were located in the lower limbs (46.6%). The most frequent subtype was Acral Lentiginous Melanoma (41.8%). Most lesions were of poor prognosis: Breslow depth greater than 4.1 mm (52.7%), ulceration (61.4%) and medium or high mitotic rate (> 30 %). The V600E mutation was identified in five patients with large, deep and ulcerated tumors, four of them had less than four years of survival. In conclusion, there was a higher frequency of melanoma in women, V600E BRAF mutation was present in patients with advanced disease (high Breslow index) and, the probability of five-year survival was less than 40%.

scholarly journals Mutations in the BRAF, NRAS, and C-KIT Genes of Patients Diagnosed with Melanoma in Colombia Population

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Luz D. Gutiérrez-Castañeda ◽  
Mauricio Gamboa ◽  
John A. Nova ◽  
Leonardo Pulido ◽  
Jose D. Tovar-Parra
Keyword(s):  
Clinicopathological Characteristics ◽  
Geographic Region ◽  
Lentigo Maligna ◽  
Histological Subtypes ◽  
Braf Gene ◽  
Tissue Samples ◽  
Acral Lentiginous Melanoma ◽  
Kit Gene ◽  
Lentigo Maligna Melanoma ◽  
Sanger Method

Introduction. Mutations in the BRAF, NRAS, and C-KIT genes have been associated with the histopathological characteristics of melanoma. Likewise, the incidence of each of these subtypes changes according to the geographical origin of the population analyzed. Objective. To determine the mutation frequency in exons 11 and 15 of the BRAF gene, exons 1 and 2 of the NRAS gene, and exons 11, 13, and 17 of the C-KIT gene and to relate it with histological subtypes in patients from a region with high levels of ultraviolet radiation. Methodology. The clinicopathological characteristics of 54 cutaneous melanoma samples were analyzed. Mutation analysis was performed via qPCR on paraffin-embedded tumor tissue samples using probes specific for the V600E mutation. Amplification of exons 11 and 15 of the BRAF gene, exons 1 and 2 of the NRAS gene, and exons 11, 13, and 17 of the C-KIT gene was performed for subsequent sequencing using the Sanger method. Result. The most frequent histological subtype in the analyzed sample was lentigo maligna/lentigo maligna melanoma (52%) followed by acral lentiginous melanoma (20%). The BRAF-V600 variant was the most frequent (63.6%). The most frequent (54%) mutation in NRAS was p.Lys5∗. In the C-KIT gene, only the Val560Ala mutation was found. Conclusion. Differences in histological subtypes and mutations in the BRAF, NRAS, and C-KIT genes were found in the analyzed population. This indicates that environmental and genetic factors significantly influence the introduction of the disease in this geographic region.

The Variant rs145204276 of GAS5 is Associated with the Development and Prognosis of Gastric Cancer

2018 ◽  
Vol 27 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Qianjun Li ◽  
Gang Ma ◽  
Huimin Guo ◽  
Suhua Sun ◽  
Ying Xu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Survival Rate ◽  
Cancer Progression ◽  
Regulatory Mechanism ◽  
Tumor Stage ◽  
Kaplan Meier ◽  
Non Coding Rna ◽  
Early Tumor ◽  
Long Non Coding Rna ◽  
Clinicopathological Variables

Background & Aims: Down-regulation of the growth arrest specific transcript 5 (GAS5) (long non-coding RNA) is associated with cell proliferation of gastric cancer (GC) and a poor prognosis. We aimed to investigate whether the variant rs145204276 of GAS5 is associated with the prognosis of GC in the Chinese population, and to unveil the regulatory mechanism underlying the GAS5 expression in GC tissues.Method: 1,253 GC patients and 1,354 healthy controls were included. The frequency of the genotype del/del and the allele del of rs145204276 were compared between the patients and the controls and between different subgroups of patients classified by clinicopathological variables. The overall survival rate was analyzed according to the Kaplan-Meier method using the log-rank test.Results: The frequency of genotype del/del was significantly lower in patients than in the controls (7.0% vs. 9.1%, p = 0.001). Kaplan-Meier analysis showed that genotype del/del was significantly associated with a higher survival rate (p = 0.01). Patients with late tumor stage were found to have a significantly lower rate of genotype del/del than those with an early tumor stage (4.9% vs. 8.8%, p = 0.01). Patients with UICC III and IV were found to have a significantly lower rate of genotype del/del than those with UICC I and II (5.3% vs. 8.1%, p = 0.02).Conclusion: The variant rs145204276 of GAS5 is associated with the development and prognosis of GC. The allele del of rs145204276 is associated with a remarkably lower incidence of cancer progression and metastasis.

scholarly journals Expression and clinical significance of miR-3615 in hepatocellular carcinoma

2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098154
Author(s):  
Xin Yuan ◽  
Yize Zhang ◽  
Zujiang Yu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Curve ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
Prognostic Information ◽  
Ki 67 ◽  
Tissue Samples ◽  
Expression Levels ◽  
Kaplan Meier ◽  
Serum Alpha Fetoprotein

Objective To investigate the association between microRNA-3615 (miR-3615) expression and the prognosis and clinicopathological features in patients with hepatocellular carcinoma (HCC). Methods We obtained clinicopathological and genomic data and prognostic information on HCC patients from The Cancer Genome Atlas (TCGA) database. We then analyzed differences in miR-3615 expression levels between HCC and adjacent tissues using SPSS software, and examined the relationships between miR-3615 expression levels and clinicopathological characteristics. We also explored the influence of miR-3615 expression levels on the prognosis of HCC patients using Kaplan–Meier survival curve analysis. Results Based on data for 345 HCC and 50 adjacent normal tissue samples, expression levels of miR-3615 were significantly higher in HCC tissues compared with adjacent tissues. MiR-3615 expression levels in HCC patients were negatively correlated with overall survival time and positively correlated with high TNM stage, serum Ki-67 expression level, and serum alpha-fetoprotein level. There were no significant correlations between miR-3615 expression and age, sex, and pathological grade. Conclusion MiR-3615 may be a promising new biomarker and prognostic factor for HCC.

scholarly journals Assessment of PI3K/mTOR/AKT Pathway Elements to Serve as Biomarkers and Therapeutic Targets in Penile Cancer

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2323
Author(s):  
Anita Thomas ◽  
Sascha Reetz ◽  
Philipp Stenzel ◽  
Katrin Tagscherer ◽  
Wilfried Roth ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Lines ◽  
Penile Cancer ◽  
Multivariate Regression Analysis ◽  
Clinicopathological Characteristics ◽  
Akt Pathway ◽  
Akt Inhibitor ◽  
Free Survival ◽  
Kaplan Meier ◽  
Treatment Naïve

The PI3K/mTOR/AKT pathway might represent an intriguing option for treatment of penile cancer (PeCa). We aimed to assess whether members of this pathway might serve as biomarkers and targets for systemic therapy. Tissue of primary cancer from treatment-naïve PeCa patients was used for tissue microarray analysis. Immunohistochemical staining was performed with antibodies against AKT, pAKT, mTOR, pmTOR, pS6, pPRAS, p4EBP1, S6K1 and pp70S6K. Protein expression was correlated with clinicopathological characteristics as well as overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS) and metastasis-free survival (MFS). AKT inhibition was tested in two primarily established, treatment-naïve PeCa cell lines by treatment with capivasertib and analysis of cell viability and chemotaxis. A total of 76 patients surgically treated for invasive PeCa were included. Higher expression of AKT was significantly more prevalent in high-grade tumors and predictive of DSS and OS in the Kaplan–Meier analysis, and an independent predictor of worse OS and DSS in the multivariate regression analysis. Treatment with pan-AKT inhibitor capivasertib in PeCa cell lines induced a significant downregulation of both total AKT and pAKT as well as decreased cell viability and chemotaxis. Selected protein candidates of the mTOR/AKT signaling pathway demonstrate association with histological and survival parameters of PeCa patients, whereas AKT appears to be the most promising one.

scholarly journals NDRG3 overexpression is associated with a poor prognosis in patients with hepatocellular carcinoma

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Ji-sheng Jing ◽  
Hongbo Li ◽  
Shun-cai Wang ◽  
Jiu-ming Ma ◽  
La-qing Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cox Regression ◽  
Survival Curve ◽  
Disease Free Survival ◽  
Prognostic Indicator ◽  
Clinicopathological Characteristics ◽  
Pcr Analysis ◽  
Kaplan Meier ◽  
Tumor Tissues ◽  
The Relationship

N-myc downstream-regulated gene 3 (NDRG3), an important member of the NDRG family, is involved in cell proliferation, differentiation, and other biological processes. The present study analyzed NDRG3 expression in hepatocellular carcinoma (HCC) and explored the relationship between expression of NDRG3 in HCC patients and their clinicopathological characteristics. We performed quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry (IHC) analyses on HCC tissues to elucidate NDRG3 expression characteristics in HCC patients. Kaplan–Meier survival curve and Cox regression analyses were used to evaluate the prognoses of 102 patients with HCC. The results revealed that compared with non-tumor tissues, HCC tissues showed significantly higher NDRG3 expression. In addition, our analyses showed that NDRG3 expression was statistically associated with tumor size (P=0.048) and pathological grade (P=0.001). Survival analysis and Kaplan–Meier curves revealed that NDRG3 expression is an independent prognostic indicator for disease-free survival (P=0.002) and overall survival (P=0.005) in HCC patients. The data indicate that NDRG3 expression may be considered as a oncogenic biomarker and a novel predictor for HCC prognosis.

scholarly journals Identification and Validation of an 6-Metabolism-Related Gene Signature and Its Correlation With Immune Checkpoint in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
He Ren ◽  
Wanjing Li ◽  
Xin Liu ◽  
Shuliang Li ◽  
Hao Guo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Gene Signature ◽  
Clinicopathological Characteristics ◽  
Gene Set Enrichment Analysis ◽  
Operating Characteristics ◽  
Kaplan Meier ◽  
Characteristics Analysis

Hepatocellular carcinoma (HCC) is a common malignant tumor with relatively high malignancy and rapid disease progression. Metabolism-related genes (MRGs) are involved in the pathogenesis of HCC. This study explored potential key MRGs and their effect on T-cell immune function in the tumor immune microenvironment to provide new insight for the treatment of HCC. Of 456 differentially expressed MRGs identified from TCGA database, 21 were screened by MCODE and cytoHubba algorithms. From the key module, GAD1, SPP1, WFS1, GOT2, EHHADH, and APOA1 were selected for validation. The six MRGs were closely correlated with survival outcomes and clinicopathological characteristics in HCC. Receiver operating characteristics analysis and Kaplan-Meier plots showed that these genes had good prognostic value for HCC. Gene set enrichment analysis of the six MRGs indicated that they were associated with HCC development. TIMER and GEPIA databases revealed that WFS1 was significantly positively correlated and EHHADH was negatively correlated with tumor immune cell infiltration and immune checkpoint expression. Finally, quantificational real-time polymerase chain reaction (qRT-PCR) confirmed the expression of WFS1 and EHHADH mRNA in our own patients’ cohort samples and four HCC cell lines. Collectively, the present study identified six potential MRG biomarkers associated with the prognosis and tumor immune infiltration of HCC, thus providing new insight into the pathogenesis and treatment of HCC.

Immunohistochemical Comparative Study of Aggressive and Non-aggressive Central Giant Cell Lesions of the Jaws Based on the Tenascin-C Expression Profile

2021 ◽  
pp. 002215542110254
Author(s):  
Sergio Iván Tobón-Arroyave ◽  
Diana María Isaza-Guzmán ◽  
Gloria Amparo Flórez-Moreno
Keyword(s):  
Logistic Regression ◽  
Giant Cell ◽  
Interstitial Fibrosis ◽  
Distribution Patterns ◽  
Clinicopathological Characteristics ◽  
Immunohistochemical Expression ◽  
Logistic Regression Models ◽  
Tenascin C ◽  
Independent Association ◽  
Clinicopathological Variables

The purpose of this study was to compare the immunohistochemical expression of tenascin-C (Tn-C) regarding clinicopathological variables and its association with the clinical behavior of central giant cell lesions (CGCLs). Forty-eight paraffin-embedded samples of CGCLs were selected. Based on clinical and radiographic features, the lesions were classified as aggressive (A-CGCLs) and non-aggressive (NA-CGCLs) subtypes. Histological assessment included the microvessel count (MVC), multinucleated giant cell (MGC) count, and the proportion of tissue area involved by mononuclear stromal cells/interstitial fibrosis. Immunoreactivity, immunolocalization, and distribution patterns of Tn-C were studied immunohistochemically. The association between Tn-C expression and clinicopathological characteristics was analyzed separately and adjusted for confounders using logistic regression models. A significantly greater proportion of cases with moderate-to-intense, intracellular, and diffuse staining of Tn-C was observed in A-CGCLs. CGCLs with a size ≥3.3 cm, fast growth, cortical disruption, high MVC/MGC counts, and low interstitial fibrosis showed a significantly greater frequency of moderate-to-intense, intracellular, and diffuse staining. Logistic regression analysis indicated a strong/independent association of these three immunohistochemical parameters with the aggressiveness of lesions. These data appear to suggest a possible role for Tn-C in the etiopathogenesis of CGCLs of the jaws, where its upregulation might favor the destructive behavior of A-CGCLs.

Analysis of real-world (RW) data for metastatic breast cancer (mBC) patients (pts) with somatic BRCA1/2 (sBRCA) or other homologous recombination (HR)-pathway gene mutations (muts) treated with PARP inhibitors (PARPi).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10512-10512
Author(s):  
Felipe Batalini ◽  
Russell Madison ◽  
Dean C. Pavlick ◽  
Ethan Sokol ◽  
Tamara Snow ◽  
...  
Keyword(s):  
Cox Regression ◽  
Gene Mutations ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Parp Inhibitors ◽  
Free Survival ◽  
Pathogenic Variants ◽  
Kaplan Meier ◽  
Pathway Gene ◽  
Comprehensive Genomic Profiling

10512 Background: PARPi are approved for treatment of pts w/ HER2-negative mBC and germline BRCA1/2 (g BRCA) pathogenic or likely pathogenic variants (muts); however, clinical benefit has also been demonstrated in mBC pts w/ sBRCA or other HR-pathway gene muts. Using a RW Clinico-Genomic Database (CGDB), we assessed outcomes for pts w/ gBRCA muts compared to pts w/ either s BRCA or other HR-pathway muts treated w/ PARPi. Methods: 6,329 mBC pts from ̃280 US cancer clinics were included in the Flatiron Health (FH) -Foundation Medicine (FM) CGDB, which includes comprehensive genomic profiling (CGP) linked to de-identified, electronic health record (EHR)-derived clinical data. Eligible pts had mBC, received care in the FH network from 1/1/2011-9/1/2020, and had tissue CGP by FM. Pts classified as gBRCA: positive germline result in EHR and BRCA mut predicted germline per FM’s somatic, germline, zygosity algorithm (SGZ) (Sun et al PMID 29415044). Non-g BRCA: negative germline results in EHR and a somatic BRCA (s BRCA) mut per SGZ or BRCA wild-type w/ another HR mut per CGP result. Pts w/o a documented gBRCA result in EHR, unknown FM BRCA SGZ result, or conflicting results were excluded. RW overall survival (rwOS) and RW progression-free survival (rwPFS) from start of PARPi for pts w/ gBRCA and non- gBRCA mBC were compared using Kaplan-Meier analysis and Cox regression adjusted for mBC line number, prior platinum, age at PARPi initiation, race, and receptor status. Results: Among pts who received PARPi in the mBC setting, 44 had gBRCA and 18 had non -gBRCA: 9 s BRCA (5 BRCA1, 4 BRCA2), 4 PALB2, 2 ATM, and 1 each of ATM+CDK12, BARD1+FANCF+RAD54L, and CHEK2. Of HR muts 76% were confirmed biallelic: 33/44 gBRCA (11 unknown), 8/9 sBRCA, 3/4 PALB2, and 3/5 other (1 unknown). Neither median rwPFS nor rwOS from start of PARPi were significantly different between the non-g BRCA and g BRCA cohorts (rwPFS: 7.0 [4.6-11.3] vs 5.5 [4.3-7.2] months (mos), aHR: 1.19 [0.57 – 2.43]; rwOS: 15.0 [7.95-16.3] vs 11.5 [9.46-NA] mos, aHR: 0.85 [0.36-1.98]). For 9 pts w/ sBRCA mut, median rwPFS was 7.1 mos (range 1.4-12.4) and all pts had progressed by data cut off. Conclusions: Despite small pt numbers and limitations from RW data, our results suggest that pts w/ biallelic non-g BRCA mBC may derive similar benefit from PARPi when tumor CGP detects a s BRCA mut or germline or somatic mut in other HR-pathway genes. These findings are consistent w/ the results from TBCRC-048 (Tung et al PMID 33119476) and support further randomized trials exploring the efficacy of PARPi in this population.[Table: see text]

Atypical presentation of rapid-onset dystonia–parkinsonism in a toddler with a novel mutation in the ATP1A3 gene

2021 ◽  
Vol 14 (8) ◽  
pp. e244152
Author(s):  
Aishwarya Ganesh ◽  
Samyuktha Sivakumar ◽  
RanjithKumar Manokaran ◽  
Udayakumar Narasimhan
Keyword(s):  
Novel Mutation ◽  
Gene Mutations ◽  
Paediatric Population ◽  
Rapid Onset ◽  
Lower Limbs ◽  
Muscle Rigidity ◽  
Atypical Presentation ◽  
Genetic Sequencing ◽  
Atypical Presentations ◽  
Atp1a3 Gene

ATP1A3 gene mutations can result in a spectrum of diseases with diverse neurological manifestations. One such disorder linked to this mutation is rapid-onset dystonia–parkinsonism (RDP), which manifests as dystonia with features of parkinsonism, such as tremors, rigidity, muscle spasms, and bulbar symptoms. Affected patients are typically adolescents or young adults, with symptoms occurring in a rostrocaudal pattern. We report a unique case of a 2-year-old child with an early onset, atypical presentation of RDP. In addition to motor developmental delay, he presented with muscle rigidity and mild asymmetric dystonia of the limbs, with the lower limbs being more affected than the upper limbs. Genetic sequencing of the child revealed a novel heterozygous autosomal dominant mutation of ATP1A3 gene c.173A>G (p. Tyr58Cys). This report highlights that RDP can present with atypical presentations in the paediatric population and adds to existing medical literature on the clinical spectrum of ATP1A3 genetic channelopathy.

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