Dataset Information

Cutaneous melanoma in Argentina: an analysis of its characteristics and regional differences.

ABSTRACT: Purpose:This study aims to increase the knowledge about the characteristics of cutaneous melanoma in Argentina, their association with the risk of having Breslow ?1 mm and mortality trends for the period 2002-2017. Patients and methods:Descriptive statistics and regression analyses were done for 10.199 cases within the Argentine Melanoma Registry in the period 2002-2018. Trends in age-standardised mortality rates (ASMR) were analysed using the Join point Regression Model. Results:Cases showed lesions mainly located in males' trunk (37%) and in females' lower limbs (29%). The level of invasion was higher in males who also showed higher mortality. Cases from the North West and North East regions showed a major risk of Breslow >1 mm and harboured CM in lower limbs more frequently than in other regions. Nearly, 25% of tumours over 2 mm were in cases aged <50 years and 37.6% in patients ?50 years. In the North West, North East and Patagonia, the frequency of cases in young people was higher than in older people. In 43% of cases, the melanoma subtype was not specified in the report. The number of superficial spreading melanomas, the most common histology, was nearly twice that of Nodular melanomas the following histology in importance (3,403 and 1,754, respectively). Melanoma mortality rates in all Argentine population increased in the elderly. Lower melanoma mortality rates were observed in the North West. In 2007-2017, ASMR decreased significantly in females (average 1.4% p/year) while it increased nonsignificantly in males (0.4% p/year).The tumours with the worst prognosis were associated with the elderly, males, nodular or acrolentiginous morphologies, residing somewhere other than Centro and Patagonia and with tumors located in the head/neck and legs. Conclusion:The geographical variations found for melanoma characteristics and their mortality in Argentina, makes it imperative that epidemiological research is continued to avoid generalisations and improve future preventive actions.

SUBMITTER: Loria D

PROVIDER: S-EPMC7105344 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Cutaneous melanoma in Argentina: an analysis of its characteristics and regional differences.

Loria Dora D Abriata María Graciela MG Santoro Federico F Latorre Clara C

Ecancermedicalscience 20200305

<h4>Purpose</h4>This study aims to increase the knowledge about the characteristics of cutaneous melanoma in Argentina, their association with the risk of having Breslow ≥1 mm and mortality trends for the period 2002-2017.<h4>Patients and methods</h4>Descriptive statistics and regression analyses were done for 10.199 cases within the Argentine Melanoma Registry in the period 2002-2018. Trends in age-standardised mortality rates (ASMR) were analysed using the Join point Regression Model.<h4>Resul ...[more]

PMID: 32256700

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Project description:Perturbations in microRNA (miRNA) expression profiles has been reported for cutaneous malignant melanoma (CMM). With regards to a rapidly growing number of newly discovered miRNA sequences, the availability of up-to-date miRNA expression profiles for primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM) and benign melanocytic naevi (BMN) is limited. Patients with PCMM (n=9), CMMM (n=4) and BMN (n=8) were included in the study. Specimens were obtained during surgery from the center of the tumors (lesional). An exploratory microarray analysis was performed by miRNA expression profiling based on miRBase V.16. Additionally, the expression levels of selected miRNA candidates were confirmed by TaqMan real-time quantitative polymerase chain reaction (RT-PCR). New miRNA candidates previously not described to be associated with CMM were found to be potentially dysregulated in CMM. Nine patients with PCMM (PCMM1-PCMM9), four patients with CMMM (CMMM1-CMMM4) and eight patients with BMN (BMN1-BMN8) were enrolled in the present study. All cutaneous specimens were harvested in the operating room, immediately stored in RNAlater (Quiagen, Hilden, Germany) and kept at - 80 °C until RNA isolation. Total RNA including miRNAs was isolated using the miRNeasy Mini Kit (Quiagen, Hilden, Germany) according to the manufacturer’s protocol. RNA concentration and purity was determined by NanoDrop ND-1000 spectral photometer (Peqlab, Erlangen, Germany). RNA integrity control (RIN) was determined by means of capillary electrophoresis with the 2100 Bioanalyzer and the RNA 6000 NanoLabCHip Kits (both Agilent Technologies, Santa Clara, USA). To be further considered for Microarray analysis a RIN ≥ 7.0 indicating medium to good RNA quality was defined as inclusion criteria. For assessment of labeling and hybridization efficiencies total RNA samples were spiked with in-vitro synthesized oligonucleotides by using the MicroRNA Spike-In Kit (Agilent Technologies, Santa Clara, USA). A total of 100 ng total RNA per sample were introduced into a labeling reaction. The spiked total RNA was treated with alkaline calf intestine phosphatase (CIP). The dephosphorylated RNA was labeled with the miRNA Complete Labeling and Hyb Kit (Agilent Technologies, Santa Clara, USA) according to the manufacturer´s instructions using T4 RNA ligase, incorporating Cyanine 3-Cytidine biphosphate (pCp). The Cyanine-3-labeled miRNA samples were prepared for One-Color based hybridization with Complete miRNA Labeling and Hyb Kit (Agilent Technologies, Santa Clara, USA) according to the manufacturer´s instructions. Labeled miRNA samples were hybridized at 55°C for 20 hrs on separate Human miRNA Microarrays Release 16.0 (8x60K format, (Agilent Technologies, Santa Clara, USA). Afterwards, microarrays were washed with increasing stringency using Gene Expression Wash Buffers (Agilent Technologies, Santa Clara, USA) followed by drying with acetonitrile (Sigma-Aldich, St.Louis, USA). Fluorescent signal intensities were detected with Scan Control A.8.4.1 Software (Agilent Technologies, Santa Clara, USA) on the Agilent DNA Microarray Scanner and extracted from the images using Feature Extraction 10.7.3.1 Software (Agilent Technologies, Santa Clara, USA). All the steps described were carried out according to the manufacturer´s instructions.

Project description:When medical diagnostic difficulties occur at local hospitals, seeking high-quality services across regions becomes a priority for many patients. Traditional statistical methods in health care are unable to account for spatial characteristics such as outflow place or distributions of disease type and patient ages in the context of an increasing number of cross-regional groups; thus, these methods are incapable of studying service utilization differences among hospitals. From a geographic perspective, we analyzed the spatial characteristics of cross-regional patient groups who travelled from other places to Beijing and the spatial decay patterns in the actual service utilization of different hospitals in Beijing by using geographic calculations, geographic visualizations, and distance decay functions. We found the following results: (1) It is feasible to study patients' cross-regional mobility from a geographical perspective. Through interdisciplinary integration, we can explore laws and conclusions that cannot be examined by traditional statistical methods in health care. (2) The characteristics of cross-regional patients who travelled from other places to Beijing were as follows: (a) Most patients came from northern China, and neoplasm treatment was the main demand of cross-regional patients; (b) patients 40-65 years old were the main cross-regional treatment group, and the average age of patients from northern regions and certain eastern coastal cities was relatively high. (3) The exponential distance decay function was the best of all five distance decay functions in fitting the distribution of cross-regional patient mobility to hospitals of different levels, types, and functional areas. The results of applying this function and the centrality calculation method showed that hospital service utilization was least affected by distance and that average radial distances (AR) were greatest in tertiary hospitals (distance decay coefficient β = 0.0786, AR = 664.70 km), traditional Chinese medicine hospitals (β = 0.0752, AR = 743.52 km), and hospitals in urban extension areas (β = 0.0782, AR = 693.29 km). Our results can serve as a reference for research concerning the allocation of medical resources and patients' choices regarding medical treatment.

Project description:The profound disparity in response to immune checkpoint blockade (ICB) by cutaneous melanoma (CM) and uveal melanoma (UM) patients is not well understood. Therefore, we characterized metastases of CM and UM from the same metastatic site (liver), in order to dissect the potential underlying mechanism in differential response on ICB. Tumor liver samples from CM (n=38) and UM (n=28) patients were analyzed at the genomic (whole exome sequencing), transcriptional (RNA sequencing) and protein (immunohistochemistry and GeoMx Digital Spatial Profiling) level. Comparison of CM and UM metastases from the same metastatic site revealed that, although originating from the same melanocyte lineage, CM and UM differed in somatic mutation profile, copy number profile, tumor mutational burden (TMB) and consequently predicted neoantigens. A higher melanin content and higher expression of the melanoma differentiation antigen MelanA was observed in liver metastases of UM patients. No difference in B2M and human leukocyte antigen-DR (HLA-DR) expression was observed. A higher expression of programmed cell death ligand 1 (PD-L1) was found in CM compared with UM liver metastases, although the majority of CM and UM liver metastases lacked PD-L1 expression. There was no difference in the extent of immune infiltration observed between CM and UM metastases, with the exception of a higher expression of CD163 (p<0.0001) in CM liver samples. While the extent of immune infiltration was similar for CM and UM metastases, the ratio of exhausted CD8 T cells to cytotoxic T cells, to total CD8 T cells and to Th1 cells, was significantly higher in UM metastases. While TMB was different between CM and UM metastases, tumor immune infiltration was similar. The greater dependency on PD-L1 as an immune checkpoint in CM and the identification of higher exhaustion ratios in UM may both serve as explanations for the difference in response to ICB. Consequently, in order to improve current treatment for metastatic UM, reversal of T cell exhaustion beyond programmed cell death 1 blockade should be considered.

Dataset Information

Cutaneous melanoma in Argentina: an analysis of its characteristics and regional differences.

Publications

Cutaneous melanoma in Argentina: an analysis of its characteristics and regional differences.

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