Papers by Julia Newton-Bishop
The Lancet Oncology, 2016
The necessary margin of excision for cutaneous melanomas greater than 2 mm in thickness is contro... more The necessary margin of excision for cutaneous melanomas greater than 2 mm in thickness is controversial. At a median follow-up of 5 years, findings from our previously published randomised trial of narrow (1 cm) versus wide (3 cm) excision margins in patients with thick cutaneous melanomas showed that narrow margins were associated with an increased frequency of locoregional relapse, but no significant difference in overall survival was apparent. We now report a long-term survival analysis of that trial. We did a randomised, open-label multicentre trial in 59 hospitals-57 in the UK, one in Poland, and one in South Africa. Patients with one primary localised cutaneous melanoma greater than 2 mm in Breslow thickness on the trunk or limbs (excluding palms or soles) were randomly assigned (1:1) centrally to receive surgery with either a 1 cm or 3 cm excision margin following an initial surgery. The randomisation lists were generated with random permuted blocks and stratified by centre and extent of initial surgery. The endpoints of this analysis were overall survival and melanoma-specific survival. Analyses were done in the intention-to-treat population. This trial was not registered because it predated mandatory trial registration. Between Dec 16, 1992, and May 22, 2001, we randomly assigned 900 patients to surgery with either a 1 cm excision margin (n=453) or a 3 cm excision margin (n=447). At a median follow-up of 8·8 years (106 months [IQR 76-135], 494 patients had died, with 359 of these deaths attributed to melanoma. 194 deaths were attributed to melanoma in the 1 cm group compared with 165 in the 3 cm group (unadjusted hazard ratio [HR] 1·24 [95% CI 1·01-1·53]; p=0·041). Although a higher number of deaths overall occurred in the 1 cm group compared with the 3 cm group (253 vs 241), the difference was not significant (unadjusted HR 1·14 [95% CI 0·96-1·36]; p=0·14). Surgical complications were reported in 35 (8%) patients in the 1 cm excision margin group and 65 (15%) patients in the 3 cm group. Our findings suggest that a 1 cm excision margin is inadequate for cutaneous melanoma with Breslow thickness greater than 2 mm on the trunk and limbs. Current guidelines advise a 2 cm margin for melanomas greater than 2 mm in thickness but only a 1 cm margin for thinner melanomas. The adequacy of a 1 cm margin for thinner melanomas with poor prognostic features should be addressed in future randomised studies. Cancer Research UK, North Thames National Health Service Executive, Northern and Yorkshire National Health Service Executive, British United Provident Association Foundation, British Association of Plastic Surgeons, the Meirion Thomas Cancer Research Fund, and the National Institute for Health and Research Biomedical Research Centre at The Royal Marsden NHS Foundation Trust.
British Journal of Dermatology
Retinoblastoma patients and their relatives appear to have an increased risk of other cancers, es... more Retinoblastoma patients and their relatives appear to have an increased risk of other cancers, especially melanoma, which represents 7% of second primaries in retinoblastoma survivors. Individuals belonging to families with the atypical mole syndrome (another family cancer syndrome with a genetic susceptibility to melanoma) have a recognizable phenotype. with many atypical melanocytic naevi. We report two families in which both retinoblastoma and melanoma occurred. It is of interest that in these families atypical melanocytic naevi were also demonstrated.
European Journal of Cancer Supplements, 2008
Herceptest 3+ or FISH positive) on survival in this otherwise very good prognostic group. The gro... more Herceptest 3+ or FISH positive) on survival in this otherwise very good prognostic group. The group were 89% ER positive, with 72% smaller than 20mm. 80% were aged over 50 and 10% received chemotherapy and 91% received endocrine therapy (tamoxifen).
Journal of Clinical Oncology
Diabetes, Jan 5, 2015
At the CDKN2A/B locus, three independent signals for type 2 diabetes risk are located in a non-co... more At the CDKN2A/B locus, three independent signals for type 2 diabetes risk are located in a non-coding region near CDKN2A. The disease-associated alleles have been implicated in reduced β-cell function, but the underlying mechanism remains elusive. In mice, β-cell specific loss of Cdkn2a causes hyperplasia whilst overexpression leads to diabetes, highlighting CDKN2A as a candidate effector transcript. Rare CDKN2A loss-of-function mutations are a cause of familial melanoma and offer the opportunity to determine the impact of CDKN2A haploinsufficiency on glucose homeostasis in humans. To test the hypothesis that such individuals have improved β-cell function, we performed oral and intravenous glucose tolerance tests on mutation carriers and matched controls. Compared with controls, carriers displayed increased insulin secretion, impaired insulin sensitivity and reduced hepatic insulin clearance. These results are consistent with a model whereby CDKN2A-loss affects a range of different ...
Cancer Prevention Research, 2015
Familial cancer, Jan 3, 2015
Germline CDKN2A mutations occur in 40 % of 3-or-more case melanoma families while mutations of CD... more Germline CDKN2A mutations occur in 40 % of 3-or-more case melanoma families while mutations of CDK4, BAP1, and genes involved in telomere function (ACD, TERF2IP, POT1), have also been implicated in melanomagenesis. Mutation of the promoter of the telomerase reverse transcriptase (TERT) gene (c.-57 T>G variant) has been reported in one family. We tested for the TERT promoter variant in 675 multicase families wild-type for the known high penetrance familial melanoma genes, 1863 UK population-based melanoma cases and 529 controls. Germline lymphocyte telomere length was estimated in carriers. The c.-57 T>G TERT promoter variant was identified in one 7-case family with multiple primaries and early age of onset (earliest, 15 years) but not among population cases or controls. One family member had multiple primary melanomas, basal cell carcinomas and a bladder tumour. The blood leukocyte telomere length of a carrier was similar to wild-type cases. We provide evidence confirming that...
Nature genetics, Jan 3, 2015
Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant me... more Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide association studies (GWAS). This meta-analysis combines 11 GWAS (5 previously unpublished) and a further three stage 2 data sets, totaling 15,990 CMM cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P…
International Journal of Cancer, 2015
Pediatric Dermatology, 2015
The eruptive disseminated form of Spitz nevi (EDSN) is the rarest variant, is cosmetically disabl... more The eruptive disseminated form of Spitz nevi (EDSN) is the rarest variant, is cosmetically disabling, and has a poorly documented natural history. We report the case of a 4-year-old boy with more than 100 Spitz nevi that have significantly regressed 8 years after onset. There is no satisfactory treatment for EDSN. There have been no reports of supervening malignancy. Our case illustrates the possibility of regression of EDSN, corroborating long-term observation as a safe and acceptable management option.
Journal of Investigative Dermatology, 2015
ABSTRACT
Oncotarget, Jan 12, 2015
Development and validation of robust molecular biomarkers has so far been limited in melanoma res... more Development and validation of robust molecular biomarkers has so far been limited in melanoma research. In this paper we used a large population-based cohort to replicate two published gene signatures for melanoma classification. We assessed the signatures prognostic value and explored their biological significance by correlating them with factors known to be associated with survival (vitamin D) or etiological routes (nevi, sun sensitivity and telomere length). Genomewide microarray gene expressions were profiled in 300 archived tumors (224 primaries, 76 secondaries). The two gene signatures classified up to 96% of our samples and showed strong correlation with melanoma specific survival (P=3x10-4), Breslow thickness (P=5x10-10), ulceration (P=9.x10-8) and mitotic rate (P=3x10-7), adding prognostic value over AJCC stage (adjusted hazard ratio 1.79, 95%CI 1.13-2.83), as previously reported. Furthermore, molecular subtypes were associated with season-adjusted serum vitamin D at diagno...
British journal of cancer, 1996
The atypical mole syndrome (AMS) phenotype, characterised by a large number of common naevi as we... more The atypical mole syndrome (AMS) phenotype, characterised by a large number of common naevi as well as atypical naevi, has been described in families with a genetic susceptibility to melanoma. However, the importance of this phenotype for melanoma in the general population has not been conclusively determined. This study was designed to examine the types and distribution of naevi as well as the prevalence of the AMS phenotype in melanoma patients in England compared with controls. A total of 426 cutaneous melanoma cases (61% of all incident cases) aged 16-75 years were recruited between 1989 and 1993 from the north-east Thames region of the UK and 416 controls from the same age group were recruited over the same period and from the same region. Each subject answered a questionnaire covering demographic details, sun exposure history and other risk factors and underwent a skin examination with total body naevus count performed by a dermatologist. The AMS phenotype was defined using a ...
International journal of cancer. Journal international du cancer, Jan 21, 2015
A high number of naevi is the most significant phenotypic risk factor for melanoma and is in part... more A high number of naevi is the most significant phenotypic risk factor for melanoma and is in part genetically determined. The number of naevi decreases from middle age onwards but this senescence can be delayed in melanoma patients. We investigated the effects of naevus number count on sentinel node status and melanoma survival in a large cohort of melanoma cases. Out of 2184 melanoma cases, 684 (31.3%) had a high naevus count (>50). High naevus counts were associated with favourable prognostic factors such as lower Breslow thickness, less ulceration and lower mitotic rate, despite adjustment for age. Naevus count was not predictive of sentinel node status. The crude 5- and 10-year melanoma specific survival rate was higher in melanomas cases with a high naevus count compared to those with a low naevus count (91.2% vs 86.4% and 87.2% vs 79%, respectively). The difference in survival remained significant after adjusting for all known melanoma prognostic factors (HR= 0.43, CI 0.21-...
British journal of hospital medicine (London, England : 2005), 2006
Melanoma is an increasingly common cancer and in order to direct preventative advice at those at ... more Melanoma is an increasingly common cancer and in order to direct preventative advice at those at risk, an understanding of susceptibility is crucial. This review summarizes what is known about common low-risk genes (such as those controlling red hair) and rare high-risk genes.
Supportive Care in Cancer, 2014
Despite the large number of people affected by melanoma, little is known about the specific needs... more Despite the large number of people affected by melanoma, little is known about the specific needs of melanoma patients. Understanding the effects of melanoma diagnosis and the specific supportive care needs of this group of patients is a necessary step towards provision of effective psychosocial care. Semi-structured interviews were carried out with 15 patients with malignant melanoma of the skin. The sample size, which was purposive, included 8 females and 7 males from 27 to 78 years old. Data were analysed using the NVIVO 8 software and principles of thematic analysis. Four major areas were identified: (a) Emotional effects due to body image, fear of the sun and uncertainty for the future; (b) Effects on Relationships, with some patients in need of more support than others from family and work colleagues; (c) Functional effects due to on-going symptoms such as pain and lymphedema; and (d) Health System and Information Needs, around the clarity, quality and timing of the information received from the health care professionals. The findings suggest that we often fail to pick up melanoma patients' health and psychosocial needs and fail to refer them appropriately, rather than the services not being available. Interventions should focus on patient and carer education about melanoma and sun protection, psychosocial support and effective information giving. Patient-reported outcome measures should routinely be collected to identify issues of specific concerns to the patients and directing them to the right services based on their individual needs.
British journal of cancer, 1998
Changes in integrin expression have been shown to be important for the growth and metastatic capa... more Changes in integrin expression have been shown to be important for the growth and metastatic capacity of melanoma cells. In this study, we have examined the expression of alphav integrins by three uveal and four cutaneous malanoma lines. No lines expressed alphavbeta6 and only TXM13, a cutaneous line, expressed alphavbeta8. All lines expressed alphavbeta5 and alphavbeta3 (four out of four cutaneous, two out of three uveal) or avpl (OM431, an uveal line). Thus, OM431 is the second uveal melanoma we have described that expresses alphavbeta1 and this, we report again, functions as an alternative vitronectin/fibronectin receptor. Subcutaneous growth of cell lines in athymic mice correlated with an alphavbeta3-positive, alphavbeta1 -negative phenotype. Analysis of clinical material from cutaneous melanoma showed that although alphav expression was increased in 88% of metastases, this could not all be explained by up-regulation of alphavbeta3, with only 2 out of eight skin metastases expr...
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Papers by Julia Newton-Bishop