ORCID Profile
0000-0001-5177-5015
Current Organisation
University of Manchester
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Publisher: Wiley
Date: 02-10-2017
DOI: 10.1111/HIS.13317
Abstract: Because the term ‘naevoid melanoma’ has variable clinical and pathological interpretations, we aimed to clarify the features of melanomas referred to as naevoid. A review was undertaken of 102 melanomas diagnosed histopathologically as naevoid melanomas and ascertained by European Organization for Research and Treatment of Cancer Melanoma Group Subcommittee pathologists from their records. We found these could be classified morphologically into three groups. Thirteen melanomas were overlying genuine naevi and were therefore excluded. Of the 89 melanomas considered to be naevoid, 11 presented clinically as exophytic papillomatous nodules with little junctional component and composed of small atypical cells showing numerous mitoses and no change with depth we termed these ‘papillomatous naevoid’ melanomas. The other 78 were flat or only slightly raised, and had a superficial spreading melanoma‐like component with maturation to a small cell, but still an atypical, dermal component we termed these ‘maturing naevoid’ melanomas. We showed that papillomatous and maturing naevoid melanomas also have differing immunochemical profiles. Preliminary clinical follow‐up suggested different outcomes for these two naevoid melanoma types. Melanomas that have been classified as naevoid melanomas comprise two types with distinct clinical, histopathological and immunohistochemical features that may also be prognostically significant.
Publisher: Springer Science and Business Media LLC
Date: 12-05-2021
DOI: 10.1038/S41467-021-22953-Z
Abstract: Ultraviolet radiation (UVR) damages the dermis and fibroblasts and increases melanoma incidence. Fibroblasts and their matrix contribute to cancer, so we studied how UVR modifies dermal fibroblast function, the extracellular matrix (ECM) and melanoma invasion. We confirmed UVR-damaged fibroblasts persistently upregulate collagen-cleaving matrix metalloprotein-1 ( MMP1 ) expression, reducing local collagen ( COL1A1 ), and COL1A1 degradation by MMP1 decreased melanoma invasion. Conversely, inhibiting ECM degradation and MMP1 expression restored melanoma invasion. Primary cutaneous melanomas of aged humans show more cancer cells invade as single cells at the invasive front of melanomas expressing and depositing more collagen, and collagen and single melanoma cell invasion are robust predictors of poor melanoma-specific survival. Thus, primary melanomas arising over collagen-degraded skin are less invasive, and reduced invasion improves survival. However, melanoma-associated fibroblasts can restore invasion by increasing collagen synthesis. Finally, high COL1A1 gene expression is a biomarker of poor outcome across a range of primary cancers.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2021
DOI: 10.1158/1078-0432.CCR-20-4261
Abstract: Cancer susceptibility and mortality are higher in males, and the mutational and transcriptomic landscape of cancer differs by sex. The current assumption is that men are at higher risk of epithelial cancers as they expose more to carcinogens and accumulate more damage than women. We present data showing women present with less aggressive primary cutaneous squamous cell carcinoma (cSCC) and early strong immune activation. We explored clinical and molecular sexual disparity in immunocompetent and immunosuppressed patients with primary cSCC (N = 738, N = 160), advanced-stage cSCC (N = 63, N = 20) and FVB/N mice exposed to equal doses of DMBA, as well as in human keratinocytes by whole-exome, bulk, and single-cell RNA sequencing. We show cSCC is more aggressive in men, and immunocompetent women develop mild cSCC, later in life. To test whether sex drives disparity, we exposed male and female mice to equal doses of carcinogen, and found males present with more aggressive, metastatic cSCC than females. Critically, females activate cancer immune-related expression pathways and CD4 and CD8 T-cell infiltration independently of mutations, a response that is absent in prednisolone-treated animals. In contrast, males increase the rate of mitosis and proliferation in response to carcinogen. Women's skin and keratinocytes also activate immune-cancer fighting pathways and immune cells at UV radiation–damaged sites. Critically, a compromised immune system leads to high-risk, aggressive cSCC specifically in women. This work shows the immune response is sex biased in cSCC and highlights female immunity offers greater protection than male immunity.
Publisher: Oxford University Press (OUP)
Date: 08-06-2020
DOI: 10.1111/BJD.19128
Publisher: Springer Science and Business Media LLC
Date: 03-12-2018
DOI: 10.1038/S41591-018-0265-6
Abstract: The melanoma genome is dominated by ultraviolet radiation (UVR)-induced mutations. Their relevance in disease progression is unknown. Here we classify melanomas by mutation signatures and identify ten recurrently mutated UVR signature genes that predict patient survival. We validate these findings in primary human melanomas in mice we show that this signature is imprinted by short-wavelength UVR and that four exposures to UVR are sufficient to accelerate melanomagenesis.
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.JAAD.2021.07.011
Abstract: The rate of growth of primary melanoma is a robust predictor of aggressiveness, but the mutational profile of fast-growing melanomas (FGMM) and the potential to stratify patients at high risk of death has not been comprehensively studied. To investigate the epidemiologic, clinical, and mutational profile of primary cutaneous melanomas with a thickness ≥ 1 mm, stratified by rate of growth. Observational prospective study. Deep-targeted sequencing of 40 melanoma driver genes on formalin fixed, paraffin-embedded primary melanoma s les. Comparison of FGMM (rate of growth > 0.5 mm/month) and nonFGMM (rate of growth ≤ 0.5 mm/month). Two hundred patients were enrolled, among wom 70 had FGMM. The relapse-free survival was lower in the FGMM group (P = .014). FGMM had a higher number of predicted deleterious mutations within the 40 genes than nonFGMM (P = .033). Ulceration (P = .032), thickness (P = .006), lower sun exposure (P = .049), and fibroblast growth factor receptor 2 (FGFR2) mutations (P = .037) were significantly associated with fast growth. Single-center study, cohort size, potential memory bias, number of investigated genes. Fast growth is linked to specific tumor biology and environmental factors. Ulceration, thickness, and FGFR2 mutations are associated with fast growth. Screening for FGFR2 mutations might provide an additional tool to better identify FGMM, which are probably good candidates for adjuvant therapies.
Publisher: Wiley
Date: 20-01-2010
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Amaya Viros.