Melanoma In Order Research Articles

Combined deep learning and machine learning models for the prediction of stages of melanoma

<p>Melanoma is deadly kind of skin cancer as it gets metastasized soon. It is really essential to recognize melanoma and start treatment at early stage. It is also necessary to determine the stage of melanoma in order to treat melanoma patients. Non-invasive technique is required to detect the stage of melanoma. Proposed system presents novel technique to classify the stages of melanoma based on thickness of tumor. This system uses dimensionality reduction technique to reduce the number of features and it also uses combine approach of deep learning (DL) and machine learning (ML) algorithm which include multilayer perception (MLP) and random forest (RF). Deep learning method is always better for training as they can reduce the need for data preprocessing and feature engineering and can provide simple trainable models built using only five or six different operations. Secondly, they are scalable, as they can be easily parallelized on GPUs or TPUs and can be trained by iterating over small batches of data. Thirdly they are reusable, so they can be trained on additional data without starting from scratch, making them viable for continuous online learning. For classification task machine learning algorithm that is, random forest is used as it decreases over fitting in decision trees and aids to increase the accuracy. Total of three algorithms were used, MLP, RF and proposed algorithm combined multilayer perception and random forest that is, MLP-RF. Among these models, the MLP-RF showed the best results in predicting melanoma stages with the accuracy of 97.42%.</p>

The Diagnosis and Management of Cutaneous Metastases from Melanoma.

Melanoma is one of the deadliest skin tumors, accounting for almost 90% of skin cancer mortality. Although immune therapy and targeted therapy have dramatically changed the prognosis of metastatic melanoma, many patients experience disease progression despite the currently available new treatments. Skin metastases from melanoma represent a relatively common event as first sign of advanced disease or a sign of recurrence. Skin metastases are usually asymptomatic, although in advanced stages, they can present with ulceration, bleeding, and superinfection; furthermore, they can cause symptoms related to compression on nearby tissues. Treatments vary from simple surgery resections to topical or intralesional local injections, or a combination of these techniques with the most recent systemic immune or target therapies. New research and studies should focus on the pathogenesis and molecular mechanisms of the cutaneous metastases of melanoma in order to shed light on the mechanisms underlying the different behavior and prognoses of different patients.

Who Will Have a Second Melanoma? A Prospective Longitudinal Study in Patients without Any Genetic Predisposition

Background: Melanoma patients have a higher risk of developing additional melanomas. Predisposing factors of a second primary melanoma in patients without any genetic predisposition are not well established. Objectives: The aim of this study was to identify risk factors related to the development of a second primary melanoma in order to know which patients should be followed up closely. Methods: A longitudinal study was performed at Hospital Gregorio Marañón (Madrid, Spain), based on follow-up data of patients diagnosed with cutaneous melanoma from 1998 to 2020. Results: After a median follow-up of 82 months, 58 out of 1523 (3.8%) patients developed a second melanoma. In 11 patients (19%), a second melanoma was diagnosed more than 10 years after their first melanoma. Second melanomas more commonly had a lower mean tumour thickness than the first ones, but 8 out of 58 (13.8%) had a higher tumour thickness than their first melanoma. Skin phototype I–II, having more than 50 melanocytic nevi, and recurrent sunburns were associated with the development of a second melanoma. In multivariate analysis, skin phototype I–II (odds ratio [OR] = 5.41; p < 0.001) and a higher number of nevi (OR = 3.44; p < 0.001) remained as independent risk factors for the development of a second melanoma. Conclusions: Patients with fair skin phototype and more than 50 melanocytic nevi are at increased risk of developing a second primary melanoma and should be closely monitored throughout their lives to detect earlier additional melanomas.

PGAM5: A necroptosis gene associated with poor tumor prognosis that promotes cutaneous melanoma progression.

Cutaneous melanoma is the deadliest type of skin cancer, and its highly aggressive and metastatic nature leads to an extremely poor prognosis. Necrotizing apoptosis, a specific form of programmed cell death, has been extensively studied in recent years. In this study, we analyzed the relationship between necroptosis-related functional genes and cutaneous melanoma in order to identify the biomarkers associated with the prognosis and progression of cutaneous melanoma. Cutaneous melanoma samples were classified into three subgroups on the basis of a necroptosis gene set. These subgroups were subjected to a prognostic survival analysis, and the greatest differences were observed between subgroups C1 and C3. Between these subgroups, 28 necrotizing apoptosis-related genes were significantly differently expressed. Among these, 16 necrotizing apoptosis-related genes were associated with cutaneous melanoma prognosis. Downscaling analysis and prognostic modeling using the least absolute shrinkage and selection operator analysis yielded nine pivotal genes and revealed phosphoglycerate translocase 5 (PGAM5) as the key gene. Then, qRT-PCR was used to verify the expression level of PGAM5. The results showed that PGAM5 was highly expressed in cutaneous melanoma tissues. In this study, a bioinformatics approach was used to identify PGAM5, a biomarker whose high expression is associated with the poor prognosis of cutaneous melanoma.

475 Diagnostic potential of circulating extracellular microvesicles in patients with primary and metastatic melanoma

Melanoma cells produce a large variety of extracellular vesicles(EVs). Purpose of this study is the evaluation of the diagnostic potential role, like predictive biomarkers of circulating EVs in peripheral blood in patients with primary and metastatic melanoma. The sample was collected by taking a blood sample before surgical removal of lesions suspected of melanoma in order to avoid artifacts due to surgery: overall it was composed of 77 consecutive patients, 12 affected by primary cutaneous melanoma, 8 by metastatic melanoma and 57 healthy controls.

471 mTORC2: therapeutic target in resistant BRAF-mutated melanoma

The PI3K/AKT/mTOR pathway plays a major role in melanoma pathogenesis and is also involved in resistance to targeted therapies (TT). The mTORC2 complex plays an important role in this pathway and therefore contributes to the development of BRAF-mutated (BRAFm) melanomas and their resistance to treatments. The goal of our project is to study this complex in melanoma in order to target it specifically. For this purpose, we are focusing more particularly on one principal protein of this complex: SIN1 (also called MAPKAP1).

Immunohistochemical study of uveal melanoma and its cellular microenvironment

Introduction. Uveal melanoma pathogenesis is determined by a number of factors, including the tumor molecular genetics, the organism’s immune response, and other ones. One of the approaches to studying the peculiarities of pathogenesis of this cancer is to determine the local subpopulations of lymphocytes and macrophages in combination with the study of the proliferative activity of tumor cells.Objective – to study the immunohistochemical features of uveal melanoma and its cellular microenvironment.Materials and methods. 24 enucleated eyes with uveal melanoma (144 histological and 216 immunohistochemicalpreparations) without previous treatment were analyzed. Cells of the immune microenvironment were analyzed: lymphocyte subpopulations and CD 68+ and CD 163+ antigens expressed by macrophages in the melanoma stroma and 2–3 mm from it. The tumor cell proliferation index Ki-67 was diagnosed.Results. All tissue samples of uveal melanoma revealed the presence of lymphocytes in the microenvironment of tumor cells. A large proportion of the studied subpopulations of lymphocytes were T-cytotoxic CD28+ lymphocytes (absolute content: 607.3 ± 431.2, relative: 18.84 % ± 12.12 %) (p = 0.018). A smaller proportion, but in equal proportions, were T-helpers CD4+, T-cytotoxic CD8+ and CD25+ lymphocytes (p = 0.6). The absolute number of natural killer cells subpopulation CD16+ was lower compared to CD56+ (p = 0.05). However, an almost equal relative content of the studied subpopulations was noted (p = 0.9). Histological examination revealed the presence of uveal melanoma macrophages in the microenvironment of the tissue. The immunohistochemical study of CD68+ and CD163+ antigens expressed by anti-inflammatory and pro-tumor macrophages showed that their absolute and relative content in the uveal melanoma tissue is almost the same with a slight predominance of CD163+ (p = 0.7). Immunohistochemical analysis showed that the nuclei of melanoma cells contain, on average, 575.2 ± 388.5 significant cells of the Ki-67 proliferation protein. This protein was found in 16.69 ± 10.88 % of tumor cells.Conclusion. Immunohistochemical study allows to identify subpopulations of lymphocytes infiltrating the tumor, to determine the subtypes of macrophages and to estimate the Ki-67 index of tumor cell proliferation. The data obtained will make it possible to further evaluate the significance of individual immune cells (in particular, T-cytotoxic CD28+ lymphocytes) in the pathogenesis of uveal melanoma in order to develop targeted effects, substantiate new immunotherapeutic approaches to the treatment of primary tumors and reprogramming altered immune cells.

Prognostic Factor Utility of BAP1 Immunohistochemistry in Uveal Melanoma: A Single Center Study in Spain.

Simple SummaryAs uveal melanoma metastasis rates are still very high, the mechanisms by which it spreads need to be evaluated. Our research sought to determine which pathological and clinical features were correlated with the prognosis of uveal melanoma in a Spanish community. BAP1 (BRCA1-Associated Protein 1) gene mutation is one of the strongest predictors for metastasis in uveal melanoma. The BAP1 protein has a tumor suppressor function and the presence of the BAP1 protein can be shown using immunohistochemical staining. Our study showed that nuclear BAP1 immunostaining had a significant correlation with survival rate in our sample, and patients with a lack of nuclear BAP1 immunostaining should be considered high-risk and receive a close follow-up. This stain can be used as routine technique in the pathological examination of uveal melanoma.Even today, the mortality rate for uveal melanoma (UM) remains very high. In our research, we sought to determine which pathological and clinical features were correlated with the prognosis of UM. BAP1 (BRCA1-Associated Protein 1) gene mutation has been analyzed as one of the strongest predictors for metastasis in UM. The BAP1 gene codifies the BAP1 protein which has a tumor suppressor function. The presence of this protein can be determined by BAP1 immunohistochemical staining. Eighty-four uveal melanoma patients and forty enucleated eyeballs were examined. Metastasis was present in 24 patients. Nuclear BAP1 staining was low in 23 patients. The presence of a higher large basal diameter tumor (p < 0.001), tumor infiltrating lymphocytes (p = 0.020), and a lack of nuclear BAP1 immunostaining (p = 0.001) ocurred significantly more often in the metastatic group. Metastasis-free survival was lower in patients with low nuclear BAP1 staining (p = 0.003). In conclusion, to the best of our knowledge, this is the first time that BAP1 staining has been studied in uveal melanoma in a Spanish community. We believe that this technique should become routine in the pathological examination of uveal melanoma in order to allow adequate classification of patients and to establish an individual follow-up plan.

Melanoma in Adolescents and Young Adults: Evaluation of the Characteristics, Treatment Strategies, and Prognostic Factors in a Monocentric Retrospective Study.

The “Veneto Cancer Registry” records melanoma as the most common cancer diagnosed in males and the third common cancer in females under 50 years of age in the Veneto Region (Italy). While melanoma is rare in children, it has greater incidence in adolescents and young adults (AYA), but literature offers only few studies specifically focused on AYA melanoma. The aim of this study was to describe the characteristics, surgical treatment, and prognosis of a cohort of AYA melanoma in order to contribute to the investigation of this malignancy and provide better patient care. This retrospective cohort study included 2,752 Caucasian patients (702 AYA and 2,050 non-AYA patients) from the Veneto Region who were over 15 years of age at diagnosis, and who received diagnosis and/or treatment from our institutions between 1998 and 2014. Patients were divided in adolescents and youth (15-25 years), young adults (26-39 years) and adults (more than 39 years) for the analysis. We found statistically significant differences in gender, primary site, Breslow thickness, ulceration, pathologic TNM classification (pTNM) stage and tumor subtype among the age groups. Disease-specific survival and disease-free survival were also different among the age groups. Our findings suggest that the biological behavior of melanoma in young people is different to that in adults, but not such as to represent a distinct pathological entity. Additional and larger prospective studies should be performed to better evaluate potential biological and cancer-specific differences between AYAs and the adult melanoma population.

Are Molecular Alterations Linked to Genetic Instability Worth to Be Included as Biomarkers for Directing or Excluding Melanoma Patients to Immunotherapy?

The improvement of the immunotherapeutic potential in most human cancers, including melanoma, requires the identification of increasingly detailed molecular features underlying the tumor immune responsiveness and acting as disease-associated biomarkers. In recent past years, the complexity of the immune landscape in cancer tissues is being steadily unveiled with a progressive better understanding of the plethora of actors playing in such a scenario, resulting in histopathology diversification, distinct molecular subtypes, and biological heterogeneity. Actually, it is widely recognized that the intracellular patterns of alterations in driver genes and loci may also concur to interfere with the homeostasis of the tumor microenvironment components, deeply affecting the immune response against the tumor. Among others, the different events linked to genetic instability—aneuploidy/somatic copy number alteration (SCNA) or microsatellite instability (MSI)—may exhibit opposite behaviors in terms of immune exclusion or responsiveness. In this review, we focused on both prevalence and impact of such different types of genetic instability in melanoma in order to evaluate whether their use as biomarkers in an integrated analysis of the molecular profile of such a malignancy may allow defining any potential predictive value for response/resistance to immunotherapy.

The association between active tumor volume, total lesion glycolysis and levels of S-100B and LDH in stage IV melanoma patients

IntroductionThe Standardized Uptake Value (SUV) in single lesions on 18F-FDG PET/CT scans and serum S-100B concentrations are inversely associated with disease-free survival in stage IV melanoma. The aim of this study was to assess the association between biomarkers (S-100B, LDH) and the PET-derived metrics SUVmean/max, metabolic active tumor volume (MATV), and total lesion glycolysis (TLG) in stage IV melanoma in order to understand what these biomarkers reflect and their possible utility for follow-up. MethodsIn 52 stage IV patients the association between PET-derived metrics and the biomarkers S-100B and LDH was assessed and the impact on survival analyzed. ResultsS-100B was elevated (>0.15 μg/l) in 37 patients (71%), LDH in 11 (21%). There was a correlation between S-100B and LDH (R2 = 0.19). S-100B was correlated to both MATV (R2 = 0.375) and TLG (R2 = 0.352), but LDH was not. Higher MATV and TLG levels were found in patients with elevated S-100B (p < 0.001) and also in patients with elevated LDH (>250 U/l) (p < 0.001). There was no association between the biomarkers and SUVmean/max. Survival analysis indicated that LDH was the only predictor of melanoma-specific survival. ConclusionIn newly diagnosed stage IV melanoma patients S-100B correlates with 18F-FDG PET/CT derived MATV and TLG in contrast to LDH, is more often elevated than LDH (71% vs. 21%) and seems to be a better predictor of disease load and disease progression. However, elevated LDH is the only predictor for survival. The biomarkers, S-100B and LDH appear to describe different aspects of the extent of metastatic disease and of tumornecrosis.

Les mélanomes d’apparition précoce (congénitaux, néonataux, du nourrisson) : revue systématique des cas de la littérature

Neonatal and infantile malignant melanoma is rare. It may be difficult to diagnose and often carries a poor prognosis. We decided to review the data on congenital, neonatal and infantile malignant melanomas in order to understand their presentation (clinical, histological, molecular), diagnosis, management and outcomes. We performed a literature search of all cases of early-onset melanoma published in PubMed from its inception to March 2019 using the following keywords: "malignant melanoma" OR "melanoma" OR "pigmented nevus" OR "malignant pigmented" AND "infantile" OR "congenital" OR "children" OR "childhood" OR "infancy" OR "neonatal". Congenital melanoma associated with maternal-foetal transmission was not included in the study. Sixty-five articles were selected and 85 cases were included in the study. Most patients were male (sex ratio: 1.6). The average age at diagnosis was 5.5 months (minimum-maximum: 0-24 months). The main site reported for congenital melanoma was the head-and-neck area and for neonatal and infantile melanoma the trunk. Half of all patients had a metastatic disease at the time of diagnosis. In metastatic cases, the prognosis was poor with the exception of patients undergoing complete excision of the tumour and metastases. The main treatment for cutaneous melanomas and operable metastasis was surgery, and secondarily, chemotherapy/immunotherapy. Neonatal and infantile malignant melanoma are rarely reported and not well-documented. It is necessary to collect additional cases to improve our knowledge of this rare disease.

The role of magnetic resonance imaging in diagnosis of uveal melanoma

AbstractPurposeTo evaluate the potential role of Magnetic Resonance Imaging (MRI) in the diagnosis of uveal melanoma.MethodsRetrospective case series involving a total of 10 patients, 9 with uveal melanoma and 1 with a suspicious melanocytic lesion, diagnosed by A‐mode and B‐mode ultrasound (US) scan. 6 of the 10 patients simultaneously performed MRI for diagnostic purposes. The results of both modalities were compared with respect to lesion dimensions, extra‐scleral extension and presence of retinal detachment (RD).ResultsIn this case series, 4 patients were diagnosed with uveal melanoma based exclusively on echographic findings and 6 patients underwent both US and MRI for diagnostic purposes. The MRI excluded the diagnosis of uveal melanoma in one patient with suspected US imaging. In the remaining 5 patients that underwent both modalities, we did not identify significant differences in lesion dimensions. Extra‐scleral extension was not identified in this subgroup by US, and MRI findings corroborated these results. With respect to RD, it was identified in 2 of these 6 subjects by US but MRI failed to identify a discrete RD in one of the subjects.ConclusionsThe present case series focused on the differences between US and MRI in the diagnosis of uveal melanoma in order to assess the potential role of MRI in such cases. We did not find any difference in diagnostic accuracy, lesion dimensions and detection of extra‐scleral extension between the two modalities, except for one patient with a suspected lesion on US that was excluded with MRI. US, however, was found to be more sensitive than MRI in the diagnosis of RD, detecting a small RD not identified by MRI. The authors identify as main limitation the small number of subjects included in the case study. Further studies involving a greater number of patients are necessary to precisely determine the role of MRI in diagnosis of uveal melanoma.

Abstract 3776: Spatially resolved immunogenomic analyses reveal diverse sub tumoral microenvironments in the context of melanoma immunotherapy

Abstract Sustained periods of apparent clinical benefit despite lack of objective response are well known in a subpopulation of advanced melanoma patients. Inter-individual heterogeneity in response of separate tumors is common, characterizing complex overall response patterns. The molecular and cellular dynamics facilitating such long-term survival and heterogeneous response is poorly understood, particularly in the era of exposure to multiple potentially active therapies. We studied an exceptional case of long-term survival in a patient with non-responding metastatic melanoma in order to characterize the clonal and microenvironmental factors active across 3 time points. We performed immunogenomic analyses of 3 metachronous tumors, including a systemic therapy-naïve mass, 67 intratumor sub-regions of a non-responding mass during PD-1 inhibitor therapy, and a post-PD-1 inhibitor mass. We profiled samples using whole exome sequencing, RNA-sequencing (RNA-seq), immunohistochemistry (IHC), and T cell receptor sequencing. Longitudinal, spatial, and cross-modal analyses were performed. Longitudinal analyses identified mutations in several genes known to be associated with targeted or immune therapy resistance affecting distinct metastases. Genomic intratumoral heterogeneity (ITH) was primarily driven by subclonal copy number alterations that showed evidence of spatially-distinct evolution which may be in response to selective pressures at the tumor margin. RNA-seq revealed an unexpectedly high degree of ITH characterized by limited group-level gene or pathway associations with physical or immune characteristics of each site. Spatially-distinct pockets of immune activation and suppression were observed throughout the PD-1 inhibitor resistant metastasis despite a largely immune-excluded phenotype seen on IHC. A specific T cell Vβ CDR3 rearrangement was identified as dominant and recurrent not only across multiple spatial points within a single tumor mass, but also across metachronous tumors spanning the patient’s disease course. Immunophenotyping of the T cell population with single-cell RNA-seq suggested repeated T-cell priming events leading to the persistence of both activated and exhausted T cells bearing the same TCR-β at any given time. Our findings highlight an unexpected level of genomic and immune heterogeneity in metastatic melanoma tumors of a long-term surviving patient. The observed degree of ITH across local tumor microenvironments reiterates the inherent limitations to identifying robust and reproducible predictive biomarkers of therapy response based on limited physical sampling of tumors. Further spatiotemporal analysis of metastatic lesions in the context of immune checkpoint blockade will be required to determine how the mechanisms driving convergent microenvironmental phenotypes may be harnessed for therapeutic gain. Citation Format: Akash Mitra, Miles C. Andrews, Whijae Roh, Mariana P. de Macedo, Alexandre Reuben, Fernando Carapeto, Feng Wang, Sangeetha M. Reddy, Khalida Wani, Christine Spencer, John Miller, Aislyn Schalck, Latasha D. Little, Donald A. Sakellariou-Thompson, Curtis Gumbs, Wen-Jen Hwu, Chantale Bernatchez, Jianhua Zhang, Patrick Hwu, Nicholas Navin, Padmanee Sharma, James P. Allison, Jennifer Wargo, Alexander J. Lazar, Philip A. Futreal. Spatially resolved immunogenomic analyses reveal diverse sub tumoral microenvironments in the context of melanoma immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3776.

Pembrolizumab for Unresectable or Metastatic Melanoma in Patients Older than 85 Years of Age

Background: Programmed cell death protein-1 (PD-1) inhibitors (pembrolizumab and nivolumab) have been approved for the treatment of advanced melanoma. Over the past decades, patients older than 85 years represent an expanding group of patients in developed countries. In France, 25% of melanomas are diagnosed in patients older than 75 years. Objective: To perform a monocentric retrospective study of patients older than 85 years and treated with pembrolizu­mab for unresectable or metastatic melanoma in order to evaluate tolerance and potential benefits of this immunotherapy. Methods: Medical records of patients treated with the PD-1 inhibitor pembrolizumab between January 2015 and January 2018 were reviewed. Results: Nine patients (6 women and 3 men) older than 85 years were included in the study. The mean age was 89.6 (85–97) years at inclusion. All patients were PS 0 or 1. The mean number of infusions was 4 (1–12). However, most patients were not able to tolerate the 4-infusion schedule. One patient refused the second infusion for personal reasons. Seven patients had grade 3 or 4 treatment-related adverse events. Conclusion: These results indicate that pembrolizumab treatment in patients older than 85 years may induce responses but is associated with a high risk of toxicity and impaired autonomy.

Abstract 5204: MYC expression and smoking as drivers of failure of immune response to melanoma

Abstract There is good evidence that an immune response to melanoma predicts better survival. We report a bioinformatic study designed to identify immune subgroups of primary melanomas in order to better understand the biology of immune cell/tumor interaction, and to identify candidate predictive biomarkers for immunotherapy. We applied an approach described by Angelova et al. to the inference of tumor immune cell infiltrates using differential expression of signature genes, in 703 primary melanoma transcriptomes from the Leeds Melanoma Cohort (LMC). Consensus clustering of immune cell scores identified 3 subgroups in LMC and replication was sought in The Cancer Genome Atlas (TCGA) data set, (primarily metastatic samples). We then used the whole transcriptomic data to explore associated biological pathways: a protein-protein interaction network analysis of genes was performed in Cytoscape plugin Reactome FIVIZ. Nodal genes were identified and the cellular origin of the gene expression signature further explored using immunohistochemistry (IHC) and in patient-derived melanoma cell culture transcriptomes. Clinicopathological and environmental factors, and immune cell scores associated with survival within immune subgroups, were then analysed using a multivariate Cox proportional hazard model. We identified three subgroups with transcriptomic patterns indicative of: low, intermediate and high immune cell infiltration. The groups were concordant with histological evidence of tumor infiltrating lymphocytes. Genes enriched in the low, compared with the high immune group, were in cell cycle, metabolic and Beta-catenin pathways. MYC was the nodal (the most influential) gene of the protein-protein interaction network in this group. In the high immune group, genes were enriched in immune pathways, including antigen processing and presentation, with the nodal gene - NFKB1. Based on the literature and our results, we hypothesised that MYC downregulates HLA-class I, hence we tested MYC correlations in the melanoma cell line transcriptomes (in which immune cells were absent). Indeed, MYC was negatively correlated with many HLA class I genes, with HLA-B having the strongest result: R=-0.57. IHC of primary tumors showed tumor nuclear expression of MYC. Reported smoking independently predicted a worse outcome for patients classified as the high immune group (HR=3.52, P=0.008). The transcriptomic analysis showed that smoking correlated with an increased Th2 cell score (P=0.03) and reduced NK56 bright score (P=0.01) in that group. We report evidence that MYC plays an important role in immune evasion in primary melanoma. The transcriptomic data support in vitro findings that MYC downregulates HLA class I expression. Furthermore, we present important results that smoking status modifies immune response in melanoma and is an independent risk factor for melanoma death. We hypothesise that smoking may impact on immunotherapy efficacy. Citation Format: Joanna Pozniak, Jeremie Nsengimana, Jon Laye, Sally O'Shea, Sabrina Schindler, Mitch Levesque, Tim Bishop, Julia Newton-Bishop. MYC expression and smoking as drivers of failure of immune response to melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5204.

Conjunctival Melanoma - Epidemiological Trends and Features.

Conjunctival melanoma is a rare but sight and life threatening malignancy. It accounts for 2%-5% of all ocular tumours and 5%-7% of all ocular melanomas with an incidence of 0.2-0.8 per million in the Caucasian population with rare cases reported in the non-Caucasians. In recent decades the incidence of uveal melanoma has been relatively stable whilst conjunctival and cutaneous melanoma have shown increasing incidence which may be connected to the result of environmental exposure to ultraviolet light. The dissimilarity in incidence between light and dark pigmented individuals observed in conjunctival melanomas compared to uveal and cutaneous melanomas may be related to differences in their histological structures and genetic profile. Recent molecular biological studies support the fact that each type of melanoma undergoes its own molecular changes and has characteristic biological behaviour. Further studies are required for each type of melanoma in order to ascertain their individual etiology and pathogenesis and based on this knowledge develop relevant preventative and treatment procedures.

Divisive influence of interleukin-1 receptor antagonist polymorphisms in melanoma patients.

The interleukin-1 receptor antagonist (IL-1RA) contributes to tumor survival and progression in multiple cancer entities. IL-1RA polymorphisms influence IL-1RA expression patterns and function. A known polymorphism was correlated with clinical outcomes in melanoma patients with particularly aggressive disease. DNA of 343 controls and 97 melanoma patients with poor prognostic indicators (time from diagnosis to death, nodal status, metastasis) was analyzed for a variable number of tandem repeat polymorphisms (VNTR) of the IL-1RA gene. Five alleles containing two (allele 2), three (allele 4), four (allele 1), five (allele 3) or six (allele 5) 86-bp repeats were targeted via PCR amplification. Genotype 1/2 is less common in the melanoma patient group vs. the control (28.8% vs. 39.6%; p = 0.06). Significant was the stage of the melanoma in order to predict the survivability (p = 0.008). The 1/1 and 1/2 genotype appeared to have lower hazards ratios than the 2/2 genotype (p > 0.05). Compared to the general population, the distribution of alleles coding for IL-1RA is different in melanoma patients. This alteration and the potential impact on tumor protein function and systemic inflammatory response may warrant further investigation.

The Role of S100A9 in Distinguishing Malignant Melanoma from Dysplastic and Common Nevi

Increased S A expression has been found at the deep invasive edge of melanomas as well as in the upper layers of the epidermis above and bordering melanomas However no studies to date have examined the potential clinical utility of using S A to differentiate between nevi and melanoma The aim of this study is to examine S A IHC expression in common nevi dysplastic nevi and melanomas in order to determine whether the S A marker could help distinguish these lesions

Posterior Uveal Melanoma

Uveal melanoma is a deadly ocular malignancy that involves predominantly the choroid. Once diagnosed, patients usually require long-term follow up to detect any local recurrence and metastatic disease to the liver, lung and skin. One must be competent at diagnosing choroidal melanoma in order to enable prompt intervention, which is critical to patient survival. When faced with the challenge of distinguishing it from an initial choroidal nevus or a nevus potentially transforming into a melanoma, especially small-sized, indicators for malignancy include presence of orange lipofuscin pigment, associated sub-retinal fluid, tumour proximity within 3mm of the optic disc, absence of halo or drusen, and symptoms of flashes, floaters or blurred vision. A comprehensive dilated fundus examination supplemented with fundus imaging such as optical coherence tomography and fundus auto-fluorescence is warranted. Ancillary testing using fluorescein and indocyanine green angiography, and ultrasonography demonstrating tumour hollowness in malignancy may also prove beneficial.