Genomic profiling of a dedifferentiated mucosal melanoma following exposure to immunotherapy
We present the case of a resected mucosal melanoma that on relapse underwent transformation to a dedifferentiated state. The relapsed tumour was phenotypically disparate and demonstrated loss of all typical melanoma-associated immunohistochemical markers. Furthermore, it demonstrated aggressive biological behaviour and immunotherapy resistance. We performed genomic profiling of the original and relapsed tumour to further elucidate the mechanisms underlying this rare phenomenon. Mass spectrometry-based single-nucleotide polymorphism genotyping technology was used to screen for mutations in the original and recurrent tumour....
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Short Communications Source Type: research
The role of ipilimumab after anti-PD-1 treatment: two case reports and a literature review
Metastatic melanoma has been historically associated with a poor prognosis; however, the therapeutic landscape has experimented and impressive change in the last years due to rapid advances in the immunotherapy field. The first immunotherapy treatment for metastatic melanoma was ipilimumab (anti-CTLA-4), which showed a significant improvement of overall survival compared to chemotherapy. However, in 2015 anti-PD-1 pembrolizumab shown an improved overall survival, progression-free survival and response rate compared to ipilimumab with either a better toxicity profile. Moreover, other immunotherapy combinations and target th...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Short Communications Source Type: research
New primary melanoma in a patient under triple therapy with vemurafenib, cobimetinib, and atezolizumab for metastatic melanoma
We present the unique case of a patient that developed an invasive NPM while under treatment with a combination of vemurafenib, cobimetinib, and atezolizumab. A 39-year-old white male was treated with vemurafenib, cobimetinib, and atezolizumab for a stage IV (T0, N3, M1) BRAF-V600E mutated malignant melanoma in the context of a clinical trial. Eight months from treatment initiation he was diagnosed with an NPM on his back that was found to be BRAF-wild type and neuroblastoma ras mutated, while he was in complete remission. Wide excision of the lesion followed, and the patient was not withdrawn from study treatment. Twenty-...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Short Communications Source Type: research
Time trends and age–period–cohort analysis of cutaneous malignant melanoma incidence rates in the Romagna Region (northern Italy), 1986–2014
In conclusion, the long-term upward incidence trend in the study area is stabilizing among women and an attenuation of the increasing trend is occurring among younger men in the most recent cohorts. These observations need to be confirmed with longer-term studies. (Source: Melanoma Research)
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Original Articles: Epidemiology of Melanoma Source Type: research
Estimated risk of progression of lentigo maligna to lentigo maligna melanoma
Little is known about the risk of progression of lentigo maligna to lentigo maligna melanoma. We determine the annual risk of progression of lentigo maligna to lentigo maligna melanoma by analysing a prospective population-based survey of recently diagnosed anterior (visible in a mirror) head and neck lentigo malignas and lentigo maligna melanomas. Six hundred eighty-two consecutive patients aged 18–80 years with non-recurrent lentigo maligna or lentigo maligna melanoma, diagnosed between 1 July 2015 and 20 April 2016, were identified from pathology notifications to the New South Wales Cancer Registry (Australia) and sen...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Original Articles: Epidemiology of Melanoma Source Type: research
External validation of the American Joint Committee on Cancer 8th edition melanoma staging system: who needs adjuvant treatment?
Now effective adjuvant therapy has arrived in melanoma, accurate staging and patient selection to optimize its risk/benefit ratio is crucial. The American Joint Committee on Cancer staging system is the most widely used and validated melanoma staging system, which recently released its 8th edition. We aimed to externally validate the prognostic and discriminatory ability for survival of the 8th edition compared to the 7th edition and evaluate prognostic factors. Prospective database of stage III melanoma (2000–2016). Prognostic factors for melanoma-specific survival and distant metastasis-free survival were analyzed. Sur...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Original Articles: Clinical Research Source Type: research
Nevi and Breslow thickness in melanoma: sex differences?
A large body of evidence in the scientific literature suggests that the numbers of common and atypical nevi are strong, independent risk factors for the occurrence of cutaneous malignant melanoma. Furthermore, some studies recently found an association between high nevus counts and an improved melanoma prognosis. The aim of this study was to investigate a possible relationship between the number of common and atypical nevi and melanoma prognostic factors. We carried out a retrospective analysis of patients with a histopathologically confirmed diagnosis of melanoma. These patients were treated at the Dermatology Clinic of t...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Original Articles: Clinical Research Source Type: research
Recurrence risk of early-stage melanoma of the external ear: an investigation of surgical approach and sentinel lymph node status
Surgical management of external ear melanoma presents unique technical challenges based on the unique anatomy and reconstruction concerns. Surgical technique, including preservation of cartilage, is variable and impact on recurrence is unclear. Our goal was to investigate surgical approach, including extent of surgical resection and sentinel lymph node biopsy (SLNB), and the impact on recurrence. In this retrospective review of primary clinical stage 1/2 external ear melanoma, demographics, tumor characteristics, surgical resection technique (including cartilage-sparing vs. cartilage removal), and SLNB results were evaluat...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Original Articles: Clinical Research Source Type: research
Genome-wide study on uveal melanoma patients finds association to DNA repair gene TDP1
Uveal melanoma is a life-threatening disease for which data on germline predisposition are essentially limited to mutations in the BAP1 gene. Many risk factors are shared between uveal melanoma and cutaneous melanoma, and these include fair skin color and light eye color. We carried out a genome-wide association study on 590 uveal melanoma patients and 5199 controls. Using a P-value limit of 10−5 we identified 11 loci with related odds ratios for the risk alleles ranging from 1.32 to 1.78. The smallest P-value in the overall analysis reached 1.07 × 10−7 for rs3759710 at 14q32.11, which is intronic to TDP1 (tyrosyl-DNA...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Original Articles: Translational Research Source Type: research
Utility of histone H3K27me3 and H4K20me as diagnostic indicators of melanoma
In this study, we performed immunohistochemistry on tissue microarrays containing 100 patient tissue spots; 18 benign nevi, 62 primary, and 20 metastatic melanoma tissues. We stained for histone H3K27me3 and histone H4K20me to ascertain whether these histone PTMs could be used to distinguish different stages of melanoma. Loss of histone H4K20me was observed in 66% of malignant patient tissues compared to 14% of benign nevi. A majority (79%) of benign nevi had low histone H3K27me3 staining, while 72% of malignant patient tissues showed either a complete loss or had strong histone H3K27me3 staining. When we analyzed the stai...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Original Articles: Translational Research Source Type: research
Evolutionarily conserved resistance to phagocytosis observed in melanoma cells is insensitive to upregulation of pro-phagocytic signals and to CD47 blockade
Therapeutic activation of macrophage phagocytosis has the ability to restrain tumour growth through phagocytic clearance of tumour cells and activation of the adaptive immune response. Our objective for this study was to evaluate the effects of modulating pro- and anti-phagocytic pathways in malignant melanoma. In order to identify evolutionarily conserved mechanisms of resistance that may be important for melanoma cell survival, we utilized a multi-species approach and examined the phagocytosis of human, mouse, and dog melanoma cells. We observed that melanoma cells from all three species displayed unexpected resistance t...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Original Articles: Basic Science Source Type: research
Low-level laser irradiation potentiates anticancer activity of p-coumaric acid against human malignant melanoma cells
This study showed that low-level laser irradiation alone is not able to kill human normal fibroblast and human melanoma cancer cells. Preirradiation followed by treatment with PCA did not change the cell viability in human fibroblast significantly but reduced the cell viability in melanoma cells presumably through the apoptosis pathway. (Source: Melanoma Research)
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Original Articles: Basic Science Source Type: research
Proliferation index and pseudoprogression as predictors of the therapeutic efficacy of suicide gene therapy for canine melanoma
In our veterinary clinical trials, the combination of systemic immunotherapy with local herpes simplex virus thymidine kinase/ganciclovir suicide gene (SG) treatment induced tumor pseudoprogression as part of a strong local antitumor response. This phenomenon could be owing to tumor inflammation, increased vascular permeability and to different tumor growth rates before, during and after SG therapy. The proliferation index (PI: the fraction of viable cells in S, G2/M, and hyperdiploid phases) would reflect the in-vivo and in-vitro proportion of proliferating melanoma cells in the absence of treatment (PIB) or in response t...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Original Articles: Basic Science Source Type: research
Ultraviolet radiation and cutaneous melanoma: a historical perspective
In this article, we summarize the research that eventually led to the classification of the full ultraviolet (UV) radiation spectrum as carcinogenic to humans. We recall the pioneering works that led to the formulation of novel hypotheses on the reasons underlying the increasing burden of melanoma in light-skinned populations. It took long before having compelling evidence on the association between UV and melanoma, in particular, the importance of UV exposure during childhood for both the occurrence of melanoma and death. The role of UVA was established only after 2005. If molecular lesions caused by UV radiation are bett...
Source: Melanoma Research - March 9, 2020 Category: Cancer & Oncology Tags: Review Article Source Type: research
The clinical characteristics of melanoma with BRAF V600R mutation: a case series study
We report our experience in treatment of seven patients with V600R-mutant melanoma, whose clinical records were available for review. Four patients in our cohort received BRAF inhibitors. Three patients demonstrated partial objective response to BRAF/MEK targeted therapy. V600R-mutant melanoma accounts for a significant number of cases even in single-institution practices. We believe that testing for BRAF-mutation status should include rare variants of this mutation. From our experience, the high rate of ulceration, male predominance and advanced age at diagnosis are features of melanoma with V600R mutation, which are simi...
Source: Melanoma Research - January 3, 2020 Category: Cancer & Oncology Tags: Short Communications Source Type: research
