Evidence for an association between cutaneous malignant melanoma and lymphoid malignancy: a population-based retrospective cohort study in Scotland.
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ABSTRACT:
SUBMITTER: McKenna DB
PROVIDER: S-EPMC2376790 | biostudies-other | 2003 Jan
REPOSITORIES: biostudies-other
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Project description:BackgroundObservational studies suggest that ulceration is considered to be a negative prognostic factor for cutaneous melanoma. However, the impact of ulceration over different subgroups (e.g. AJCC Stage, thickness level) are controversial and its true causal effect on survival is lack of studies in the view of treating ulceration as an exposure.ObjectiveTo explore the true causal effect of ulceration on melanoma's survival by adopting a combination of methods to discover proper adjustment set and confirming its correctness through a variety of means.MethodsA minimal sufficient adjustment set (MSAS) was found using directed acyclic graphs (DAG) to adjust the effect of causality. Sensitivity analysis was conducted to diagnose potential confounders in addition to MSAS. Cox models were built to analyze the causality in-depth and the model was validated using a novel method. Lastly, stratified effects of ulceration were examined to illustrate its impact within subgroups.ResultsHazard ratio (HR) of ulceration after adjustment by MSAS variables was 1.99 (95% CI=1.88-2.09). The sensitivity analysis of propensity score matching and E-value both demonstrated that variables other than MSAS do not have great influence on ulceration and MSS relationship. The HR of ulceration in AJCC Stage, thickness level, invasion level and tumor extension were all monotonically decreased from 5.76 to 1.57, 4.03 to 1.78, 2.75 to 1.78 and 2.65 to 1.71 respectively.ConclusionUlceration in all subgroups were shown to have a significantly negative impact on MSS and its magnitude of effect was monotonically decreased as the disease progressed. The true effect of ulceration can be adjusted by MSAS and its correctness was validated through a variety of approaches.
| S-EPMC9666370 | biostudies-literature
Project description:A novel human protoparvovirus related to human bufavirus and preliminarily named cutavirus has been discovered. We detected cutavirus in a sample of cutaneous malignant melanoma by using viral enrichment and high-throughput sequencing. The role of cutaviruses in cutaneous cancers remains to be investigated.
| S-EPMC5324802 | biostudies-literature
Project description:An historical population-based cohort study was conducted aiming to estimate the incidence of cutaneous malignant melanoma in the South Region of Portugal between Jan 2016 and June 2017; to clinically characterize the diagnosed individuals; to describe instituted treatment; and to estimate survival outcomes. Data were extracted from a cancer registry (ROR-Sul) covering 4,800,000 inhabitants (46% of the Portuguese population) and included a total of 789 individuals meeting eligibility criteria. The crude incidence rate (18 months) of melanoma was 13.36/100,000 inhabitants and the Age-Standardized Incidence Rate per 100,000 World population was 9.65/100,000 inhabitants. The most common histological subtypes identified were superficial extension, followed by malignant melanoma and nodular melanoma. Most cases were diagnosed in stage I (50.39%), equally distributed by sex and with a median age of 65 years. During the study period, 174 recurrence events were recorded (23.45%) and recurrence-free survival rate was significantly lower in more advanced stages. Patients had a two-fold risk of recurrence/death when in presence of ulcerated tumors [adjusted hazard ratio (adj HR) = 2.28; 95% confidence interval (CI) 1.40-3.70]. Overall survival rate at 3-years was 80.54% (95% CI 77.58-83.15), higher than previous national reports, and considerably higher for individuals diagnosed at earlier stages (p < 0.001). We have also identified differential survival outcomes in stages II-III explained by the uptake of sentinel lymph node biopsy. The epidemiologic and clinical characteristics of malignant melanoma patients studied are consistent with international literature. The incidence and rates observed suggests additional public health campaigns are needed to modify behaviours of the Portuguese population and thus reduce their risk.
| S-EPMC10079850 | biostudies-literature
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.
| S-ECPF-GEOD-34460 | biostudies-other
Project description:RET proto-oncogene encodes a receptor tyrosine kinase whose ligand is glial cell line-derived neurotrophic factor (GDNF), and its polymorphism at G691S juxtamembrane region (RETp) is a germline polymorphism. Cutaneous melanomas, particularly the desmoplastic subtype, are highly neurotropic; thus we sought to determine the frequency of RETp in cutaneous melanoma and its functional responsiveness to GDNF. RETp was assessed in 71 non-desmoplastic cutaneous melanomas (non-DMs) and 70 desmoplastic melanomas (DMs). Melanoma cell lines with RETp, RET wild type (RETwt), BRAF V600E mutation (BRAFmt) or BRAF wild type (BRAFwt) were assessed for functional activity. RETp frequency was significantly higher in DMs (61%) than in non-DMs (31%, P<0.001). BRAFmt was detected in only 11% of DMs. GDNF stimulation significantly amplified cell proliferation, migration and invasion in RETp, but not in RETwt melanoma cells. GDNF stimulation of RETp cell lines enhanced phosphorylation of extracellular signal-regulated kinase (ERK) and Akt of the RET-RAS-RAF-ERK and RET-phosphatidylinositol 3-kinase (PI3K)-Akt pathways, respectively. GDNF response of RETp cells in signal transduction and other functional studies were not affected by BRAFmt. The study demonstrates that RETp is frequently found in cutaneous melanoma, particularly desmoplastic subtypes, and responds to GDNF inducing events favorable for tumor progression.
| S-EPMC2738597 | biostudies-literature
Project description:PurposeCitrus products are widely consumed foods that are rich in psoralens and furocoumarins, a group of naturally occurring chemicals with potential photocarcinogenic properties. We prospectively evaluated the risk of cutaneous malignant melanoma associated with citrus consumption.MethodsA total of 63,810 women in the Nurses' Health Study (1984 to 2010) and 41,622 men in the Health Professionals Follow-Up Study (1986 to 2010) were included. Dietary information was repeatedly assessed every 2 to 4 years during follow-up. Incident melanoma cases were identified through self-report and confirmed by pathologic records.ResultsOver 24 to 26 years of follow-up, we documented 1,840 incident melanomas. After adjustment for other risk factors, the pooled multivariable hazard ratios for melanoma were 1.00 for overall citrus consumption < twice per week (reference), 1.10 (95% CI, 0.94 to 1.30) for two to four times per week, 1.26 (95% CI, 1.08 to 1.47) for five to six times per week, 1.27 (95% CI, 1.09 to 1.49) for once to 1.5 times per day, and 1.36 (95% CI, 1.14 to 1.63) for ≥ 1.6 times per day (Ptrend < .001). Among individual citrus products, grapefruit showed the most apparent association with risk of melanoma, which was independent of other lifestyle and dietary factors. The pooled multivariable hazard ratio for melanoma comparing the extreme consumption categories of grapefruit (≥ three times per week v never) was 1.41 (95% CI, 1.10 to 1.82; Ptrend < .001).ConclusionCitrus consumption was associated with an increased risk of malignant melanoma in two cohorts of women and men. Nevertheless, further investigation is needed to confirm our findings and explore related health implications.
| S-EPMC4979231 | biostudies-literature
Project description:Cutaneous melanoma is a lethal malignancy that arises spontaneously or via in situ precursor neoplasms. While melanoma in situ and locally invasive malignant melanoma can be cured surgically, these lesions can sometimes be difficult to distinguish from melanocytic nevi. Thus, the identification of histolopathologic or molecular features that distinguish these biologically distinct lesions would represent an important advance. To this end, we determined the abundance of melanocytic primary cilia in a series of 62 cases composed of typical cutaneous melanocytic nevi, melanoma in situ, invasive melanoma, and metastatic melanoma. Primary cilia are sensory organelles that modulate developmental and adaptive signaling and notably, are substantially depleted from the neoplastic epithelium of pancreatic carcinoma at a stage equivalent to melanoma in situ. In this series, we find that while nearly all melanocytes in 22 melanocytic nevi possessed a primary cilium, a near-complete loss of this organelle was observed in 16 cases of melanoma in situ, in 16 unequivocal primary invasive melanomas, and in 8 metastatic tumors, each associated with a cutaneous primary lesion. These findings suggest that the primary cilium may be used to segregate cutaneous invasive melanoma and melanoma in situ from melanocytic nevi. Moreover, they place the loss of an organelle known to regulate oncogenic signaling at an early stage of melanoma development.
| S-EPMC3214062 | biostudies-literature
Project description:Despite being rarely reported, improved diagnostic and prognostic indicators are necessary for treating malignant melanoma in rabbits. In this study, two cases of primary skin lesions, on the scrotum and on eyelid, with systemic metastases, were examined. The tumors formed intra-dermally by sheet-like proliferation of polymorphic cells, with anisocytosis and varying amount of melanin granules. Tumors had displaced almost 50% of the lung and liver tissue, and tumor metastasis was the cause of early death in both rabbits. Ki-67-positive population was high in both, and it was found to be useful in assessing the outcome and malignancy. In addition, Melan-A, HMB-45, PNL2 and S100 established a useful immunohistochemical panel for the diagnosis of melanocytic tumor in rabbits.
| S-EPMC6021888 | biostudies-other
Project description:BackgroundWorldwide, the incidence of cutaneous melanoma has been reported to be highest in the summer and lowest in the winter. Northern Irish data suggested seasonal variation for women only, especially those with thinner melanomas, sited on limbs. We interrogated two larger UK cancer registries for temporal differences in melanoma diagnosis and associated patient characteristics.MethodsMelanomas diagnosed from 2006 to 2010 in the Eastern England and Scottish cancer registries (n=11,611) were analysed by month of diagnosis, patient demographics and melanoma characteristics, using descriptive and multivariate modelling methods.ResultsMore patients with melanoma were diagnosed in the summer months (June 9.9%, July 9.7%, August 9.8%) than the winter months (December 7.2%, January 7.2%, February 7.1%) and this pattern was consistent in both regions. There was evidence that the seasonal patterns varied by sex (p=0.015), melanoma thickness (p=0.002), body site (p=0.006), and type (superficial spreading melanomas p=0.005). The seasonal variation was greatest for diagnosis of melanomas occurring on the limbs.ConclusionThis study has confirmed seasonal variation in melanoma diagnosis in Eastern England and Scotland across almost all population demographics and melanoma characteristics studied, with higher numbers diagnosed in the summer months, particularly on the limbs. Seasonal patterns in skin awareness and related help-seeking are likely to be implicated. Targeted patient interventions to increase sun awareness and encourage year-long skin inspection are warranted.
| S-EPMC4542219 | biostudies-literature
Project description:The recent past has witnessed unprecedented clinical progress in the treatment of advanced malignant melanoma through targeting of mutant BRAF in approximately 50% of patients and immune check point blockade in all patients. As has been well documented, responses to targeted therapy are of limited duration, and rates of clinical benefit to immunotherapy are modest. Given these factors, palliation of patients with chemotherapy remains an essential aspect of melanoma oncology. Many chemotherapeutics (and combinations with other agents, such as immunotherapy) have been evaluated in melanoma, although no chemotherapy regimen has been documented to provide an overall survival benefit in a prospective, randomized, well-controlled phase III study. We provide an overview of the development of the most common chemotherapy regimens for melanoma, discuss the clinical trial evidence supporting and contrasting them, and highlight appropriate clinical situations in which they might be used. We also discuss the future of chemotherapy for melanoma, noting the potential for combinations of chemotherapy with either targeted or immunotherapeutic agents.
| S-EPMC3709980 | biostudies-literature