Publications by authors named "Delphine Legoupil"

16 Publications

  • Page 1 of 1

Laparoscopy-assisted immediate vaginal reconstruction with a vertical pedicled deep inferior epigastric perforator flap for primary melanoma of the vagina.

Clin Case Rep 2021 Jun 24;9(6):e04183. Epub 2021 Jun 24.

Plastic and Reconstructive Surgery Department Brest University Hospital Brest France.

The vagina is a rare site for primary melanoma. Here, we report on a case of laparoscopy-assisted immediate vaginal reconstruction with vertical pedicled deep inferior epigastric perforator flap.
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http://dx.doi.org/10.1002/ccr3.4183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223693PMC
June 2021

Late-onset adverse events under anti-PD1 therapy in melanoma patients: an observational study from MELBASE, a nationwide prospective cohort.

J Am Acad Dermatol 2021 Jun 18. Epub 2021 Jun 18.

CHU and UMR 1098, Besançon;. Electronic address:

The purpose was to evaluate late-onset AEs in melanoma patients treated with anti-PD1 administered at least 2 years in a real-life setting. Patients were screened from MelBase (NCT02828202), a French multicentric biobank dedicated to the prospective follow-up of unresectable stage III or IV melanoma. 119 patients who received anti-PD1 during at least 2 years from January 2013 to November 2019 were included. Median follow-up was 41.7 months (25.2-57.5). Patients received nivolumab (n=53) or pembrolizumab (n=66). AEs occurred in 99 patients (83%) with a median time of 13.3 months (0-53.9), including severe AEs (grade 3 or 4) in 30 patients (30%). Late-onset AEs, mostly grade 1-2, occurred in 51 (43%) patients and led to 5 (4%) hospitalizations of which 4 were severe. Factors associated with late-onset AEs in multivariate analysis were early-onset AEs (within the first two years of treatment) and treatment duration (p=0,02 and p=0,03 respectively). Our data demonstrate the possibility of late-onset AEs occurring after 2 years of anti-PD1 therapy. Late-onset AEs appear frequent and mostly mild or moderate. Early-onset AEs and prolonged anti-PD1 treatment may increase the risk of late-onset AEs.
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http://dx.doi.org/10.1016/j.jaad.2021.06.849DOI Listing
June 2021

The prognostic significance of PD-L1 expression on tumor and immune cells in Merkel cell carcinoma.

J Cancer Res Clin Oncol 2021 Sep 11;147(9):2569-2578. Epub 2021 Jun 11.

Radiation Oncology Department, University Hospital Morvan, 2 avenue Foch, 29200, Brest, France.

Introduction: The aim of this study was to evaluate prognostic factors in patients with non-metastatic Merkel cell carcinoma (MCC), with a particular focus on immunological markers such as TILs subtyping (CD3, CD8, CD68, FoxP3, PD-L1 and PD-1) and MCPyV.

Methods: Patients treated for a non-metastatic MCC with oncologic surgical resection followed or not by adjuvant radiotherapy between 01/2007 and 12/2018 were analyzed. Local and regional control (LC, RC), distant metastasis-free survival (DMFS) and overall survival (OS) were evaluated. Clinical variables analyzed included age, gender, performance status, comorbidity, tumor size, location and presentation type, extension, oncologic resection and adjuvant radiotherapy. Pathological variables analyzed included type of tumor-infiltrating lymphocytes, CD3, CD8, CD68, PD-L1 expression on immune cells and tumors cells, PD-1, FoxP3 and MCPyV, assessed with immunohistochemistry (IHC).

Results: 77 patients were included. After a median follow-up of 18 months (range 0.2-144), the 1-year LC, RC, DMFS and OS were 83%, 60%, 82% and 75%, respectively. In multivariate analysis, a percentage of PD-L1 expression by immune cells ≥ 1% was significantly correlated with improvement of RC (p = 0.012), DMFS (p = 0.003) and OS (p = 0.006). Adjuvant radiotherapy significantly improved DMFS (p = 0.021) and OS (0.041) rates. There was a correlation between the presence of MCPyV + and the expression of PD-L1 on IC (p = 0.05) and TC (p = 0.03).

Conclusion: PD-L1 expression by immune and tumor cells in non-metastatic MCC seems to significantly improve outcome in patients who did not received PD-1/PD-L1 inhibitors. Prospective studies are needed to confirm our hypothesis.
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http://dx.doi.org/10.1007/s00432-021-03676-6DOI Listing
September 2021

Causes of Pruritus in Patients Treated With Immune Checkpoint Inhibitors for Melanomas or Skin Carcinomas.

Front Med (Lausanne) 2021 9;8:632683. Epub 2021 Feb 9.

Department of Dermatology, University Hospital of Brest, Brest, France.

Pruritus is a frequent adverse event during the use of immune checkpoint inhibitors (ICIs), with a frequency estimated to be between 11 and 47%. The underlying causes remain poorly understood. The main goal was to search for putative causes of pruritus occurring in patients treated with ICIs for melanomas and cutaneous carcinomas. Other objectives were to assess the association between the occurrence of pruritus and survival and between the occurrence of pruritus and other adverse events. A monocentric retrospective descriptive study was performed using data for patients treated with ICIs (nivolumab, pembrolizumab, ipilimumab, and cemiplimab) between August 2010 and November 2019. A total of 181 patients were included (mean age: 69 years). Pruritus was reported by 25 patients (13.8%). We were able to determine three subgroups of pruritus causes under ICI use: pruritus directly related to immunotherapy, pruritus indirectly related through other pruritus-inducing side effects and pruritus unrelated to ICIs. In 6/25 patients, no more specific cause of pruritus was found at the onset of pruritus or in their backgrounds, other than ICI use. The study has some limitations due to unicentric and retrospective design. Pruritus was found in 25/181 patients in this series; only in 6/25 patients no potential cause other than ICI could be found, and pruritus was not associated with differences in survival.
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http://dx.doi.org/10.3389/fmed.2021.632683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900003PMC
February 2021

Teledermatology in Times of COVID-19 Confinement: Comparing Patients' and Physicians' Satisfaction by the Standardized Brest Teledermatology Questionnaire.

Dermatology 2021 Feb 10:1-6. Epub 2021 Feb 10.

Univ Brest, LIEN, Brest, France.

The French government imposed the first COVID-19 pandemic lockdown from March 17 until May 11, 2020. Only emergency cases and teledermatology (TD) were allowed in outpatient settings. A standardized questionnaire was developed to compare the satisfaction level of patients and their treating physicians. Our main question was whether the patients would perceive TD as a valid alternative for direct physical face-to-face consultation. Eighty-two patients and their 4 treating dermatologists from one dermatology department participated in the study (43 females, 39 males) with a mean age of 46.6 years (SD ±23.9). The reason for TD was a chronic disease in the majority (87.8%), and mainly as a follow-up (96.3%). Regarding satisfaction, almost all categories rated around 9 on a 0-10 verbal analogue scale. The same level of global satisfaction could be seen between the patients and the physicians as well as for the quality of the patient-physician relation and whether all questions could be addressed during the TC. Physicians showed significantly higher scores than patients only for the category of "length" of the consultation. Gender, age, as well as distance between the clinic and home of the patient were not influencing factors for satisfaction. Regarding the technical parameters, the evaluation was mostly comparable for patients and physicians, but overall lower than the relational satisfaction parameters, especially for image quality. Patients were significantly more motivated to continue the TD after the lockdown than their treating dermatologists. We see an interest for implementing TD in specialized centers with chronic patients coming from remote places for regular follow-ups. TD cannot replace in-person patient-physician interaction, but was helpful during the lockdown. As a result, TD might become part of dermatology training to prepare for future lockdown situations.
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http://dx.doi.org/10.1159/000514029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018192PMC
February 2021

Phase II Study of Pembrolizumab As First-Line, Single-Drug Therapy for Patients With Unresectable Cutaneous Squamous Cell Carcinomas.

J Clin Oncol 2020 09 30;38(26):3051-3061. Epub 2020 Jul 30.

Assistance Publique-Hôpitaux de Paris, Agence Générale des Equipements et Produits de Santé, Paris, France.

Purpose: To evaluate first-line pembrolizumab monotherapy efficacy and safety in patients with unresectable cutaneous squamous cell carcinomas (CSCCs).

Patients And Methods: Patients, predominantly men, with their CSSCs' immunohistochemically determined programmed cell death-ligand 1 (PD-L1) status determined (tumor proportion score threshold, 1%), received pembrolizumab (200 mg every 3 weeks). The primary endpoint was the 39-patient primary cohort's objective response rate at week 15 (ORR). Secondary objectives were best ORR, overall survival (OS), progression-free survival (PFS), duration of response (DOR), safety, ORR according to PD-L1 status and health-related quality of life using Functional Assessment of Cancer Therapy-General (FACT-G) score. An 18-patient expansion cohort, recruited to power the study to evaluate the ORR difference between PD-L1+ and PD-L1- patients, was assessed for ORR, disease control rate, and safety, but not survival.

Results: Median age of all patients was 79 years. The primary cohort's ORR was 41% (95% CI, 26% to 58%), including 13 partial and 3 complete responses. Best responses were 8 partial and 8 complete responses. At a median follow-up of 22.4 months, respective median PFS, DOR, and OS were 6.7 months, not reached, and 25.3 months, respectively. Pembrolizumab-related adverse events affected 71% of the patients, and 4 (7%) were grade ≥ 3. One death was related to rapid CSCC progression; another resulted from a fatal second aggressive head and neck squamous cell carcinoma diagnosed 15 weeks postinclusion. ORR for the entire population was 42%; it was significantly higher for PD-L1+ patients (55%) versus PD-L1- patients (17%; = .02). Responders' W15 total FACT-G score had improved ( = .025) compared with nonresponders.

Conclusion: First-line pembrolizumab monotherapy exhibited promising anti-CSCC activity, with durable responses and manageable safety. PD-L1 positivity appears to be predictive of pembrolizumab efficacy.
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http://dx.doi.org/10.1200/JCO.19.03357DOI Listing
September 2020

Association of Anti-Programmed Cell Death 1 Antibody Treatment With Risk of Recurrence of Toxic Effects After Immune-Related Adverse Events of Ipilimumab in Patients With Metastatic Melanoma.

JAMA Dermatol 2020 09;156(9):982-986

Department of Oncology, Comprehensive Cancer Center Eugène Marquis, Rennes, France.

Importance: Since 2011, many patients with metastatic melanoma have been treated with ipilimumab therapy and have developed severe immune-related adverse events (AEs). Because several immune therapies are now available to treat metastatic melanoma, a better knowledge of mechanisms and recurrence risks of immune-related AEs is needed before reintroduction of immunotherapies.

Objectives: To evaluate the risk of a recurrence of immune toxic effects associated with anti-programmed cell death 1 antibody (anti-PD-1) therapy after discontinuation of ipilimumab monotherapy because of severe AEs.

Design, Settings, And Participants: This cohort study conducted at 19 French melanoma referral centers included patients with metastatic melanoma who experienced severe immune-related AEs after ipilimumab therapy and then were treated with anti-PD-1 therapy between February 1, 2013, and December 31, 2016. The study cutoff was June 1, 2017. Statistical analysis was performed from June 1, 2016, to August 31, 2017.

Exposures: Monotherapy with at least 1 cycle of ipilimumab that was associated with a grade 3 or 4 immune-related AE and subsequent treatment with at least 1 cycle of an anti-PD-1 (nivolumab or pembrolizumab) therapy.

Main Outcomes And Measures: The primary outcome was the rate of immune-related AEs associated with anti-PD-1 therapy. Secondary outcomes were characteristics of ipilimumab-related and anti-PD-1 immune-related AEs and overall response rate and overall survival associated with anti-PD-1 therapy.

Results: Of 56 patients with metastatic melanoma included in the study, all of whom experienced severe immune-related AEs after ipilimumab therapy (31 [55%] male; mean [SD] age, 64 [14.9] years), 20 (36%) experienced at least 1 immune-related AE associated with pembrolizumab (6 of 20 [30%]) or nivolumab (14 of 20 [70%]) therapy. A total of 12 patients (21%) experienced grade 3 or 4 immune-related AEs, and among these patients, 4 (33%) presented with the same immune-related AE as with ipilimumab therapy. Severe immune-related AEs were resolved with use of systemic corticosteroids (7 [58%]) and/or anti-tumor necrosis factor (1 [8%]), and no grade 5 toxic effects were reported. Five patients discontinued anti-PD-1 therapy because of immune-related AEs. The overall response rate was 43%, with a median overall survival of 21 months (interquartile range, 18 to ongoing).

Conclusions And Relevance: The findings suggest that anti-PD-1 therapy may be associated with reduced risk of toxic effects and improved survival among patients who have experienced severe toxic effects after ipilimumab therapy.
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http://dx.doi.org/10.1001/jamadermatol.2020.2149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364335PMC
September 2020

PD-L1 Copy Number Variation Does Not Correlate With PD-L1 Expression or Response to Anti-PD-1 Immunotherapy In Patients With Advanced Melanomas.

Appl Immunohistochem Mol Morphol 2020 02;28(2):161-165

Department of Pathology, CHRU Brest.

Predicting the response to PD-1/PD-L1 immune checkpoint blockade in patients with metastatic melanoma remains challenging. In this study, we have investigated for the relationships between PD-L1 expression, PD-L1 copy number variations, and the response to anti-PD-1 therapies. We studied the formalin-fixed paraffin-embedded tumor samples of 36 patients with metastatic melanoma using PD-L1 immunohistochemistry (IHC) and PD-L1/chromosome 9 fluorescent in situ hybridization (FISH). PD-L1 IHC was positive in 3 patients (8.33%, with >5% stained tumor cells) and PD-L1 FISH test revealed 5 (13.8%) PD-L1 amplifications, 8 (22.2%) PD-L1 gains, and 2 (5.5%) PD-L1 losses. Among 14 responders and 13 nonresponders to anti-PD-1 immunotherapy, we concluded that there was no significant relationship between PD-L1 expression, PD-L1 copy number variations, and the response to anti-PD-1 therapies. In our study, the determination of PD-L1 expression using IHC and PD-L1 copy number using FISH was insufficient to predict the response to PD-1/PD-L1 immune checkpoint blockade in patients with advanced melanomas.
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http://dx.doi.org/10.1097/PAI.0000000000000712DOI Listing
February 2020

Quality-of-life assessment in French patients with metastatic melanoma in real life.

Cancer 2020 02 22;126(3):611-618. Epub 2019 Oct 22.

Biostatistics and Epidemiology Service, Gustave Roussy Institute, Villejuif, France.

Background: Significant progress was recently observed in the treatment of metastatic melanoma (MM). With >50% of patients now reaching a second line of treatment and a significant improvement in the survival rate, an assessment of quality of life (QoL) during the whole course of the disease becomes necessary. The objective of this study was to describe the QoL of patients with MM in France, from their diagnosis of advanced disease to their death, in real life.

Methods: QoL data were collected through MelBase, a prospective, French, multicentric cohort dedicated to the follow-up of adults with MM. QoL was assessed using the EuroQoL-5D questionnaire and the Functional Assessment of Cancer Treatment (FACT)-Melanoma questionnaire at the time of study inclusion, every 3 months, and at the time of each treatment change until death. To assess longitudinal changes from baseline to death, mixed-effect models for repeated-measures analyses were used to control for baseline covariates.

Results: QoL was assessed in 1435 patients who were included in the study between 2013 and 2018. The median follow-up was 9.4 months, and 47% of patients died during follow-up. During first-line treatment, the model-based, mean utility score was 0.830 (95% CI, 0.818-0.843), the mean FACT-General score was 77.22 (95% CI, 76.23-78.22), and the mean FACT-Melanoma score was 129.46 (95% CI, 128.02-130.90). At the time of a change in treatment line, there was a decrease of -0.027 (95% CI, -0.03, -0.02) in the utility score, -1.82 (95% CI, -1.88, -1.76) in the FACT-General score, and -2.98 (95% CI, -3.05, -2.91) in the FACT-Melanoma score compared with first-line treatment.

Conclusions: In the MelBase cohort, the QoL among patients with MM seems to be fairly stable over the whole disease course, although a small but significant decrease at time therapy is changed is observed.
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http://dx.doi.org/10.1002/cncr.32554DOI Listing
February 2020

Ingenol mebutate to treat lentigo maligna of the head (face and scalp): A prospective, multicenter, single-arm phase 2 trial indicates no benefit.

J Am Acad Dermatol 2020 03 17;82(3):731-733. Epub 2019 Jul 17.

Department of Dermatology, Archet Hospital, Université Côte d'Azur, Centre Hospitalier Universitaire de Nice, Nice, France; Team 12, Centre Méditerranéen de Médecine Moléculaire, INSERM, U1065, Université Côte d'Azur, Centre Hospitalier Universitaire de Nice, Nice, France.

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http://dx.doi.org/10.1016/j.jaad.2019.07.035DOI Listing
March 2020

Association of Time From Primary Diagnosis to First Distant Relapse of Metastatic Melanoma With Progression of Disease and Survival.

JAMA Dermatol 2019 06;155(6):673-678

Department of Dermatology, Hôpital St Louis, Paris, France.

Importance: The prognosis of advanced melanoma has been greatly improved by new therapeutic agents and clinicians rely on dynamic signals to drive their therapeutic choices. Although the kinetics of metastatic disease seem to be correlated with survival, progression of the localized disease is not predictable.

Objective: To assess whether progression of metastatic disease is associated with the time to the first distant recurrence of melanoma.

Design, Setting, And Participants: This study was conducted from March 1, 2013, to September 1, 2017, among 638 adults with unresectable stage III or IV melanoma within the French multicentric prospective cohort MelBase. Patients treated with first-line immunotherapies, targeted therapies, or chemotherapy were included. Patients with unknown primary or de novo metastatic melanoma were not included. Data were analyzed from March 1, 2013, to December 1, 2017.

Main Outcomes And Measures: The date of primary excision and time to first distant recurrence, progression-free survival, and overall survival were collected. Cox proportional hazards regression models were planned to assess the association between time to first distant recurrence and progression-free survival or overall survival, which was evaluated in terms of hazard ratio (HR). Time to recurrence was analyzed both as a continuous and categorical variable (<12 months, 12-24 months, and >24 months).

Results: A total of 638 patients (272 women and 366 men; median age, 64 years [interquartile range, 52-73 years]) were included in the study. The median time from primary excision to first distant recurrence was 25 months (interquartile range, 12-55 months). There was no evidence of association of the time to recurrence with progression-free survival, both when analyzed as a continuous variable (HR, 0.99; 95% CI, 0.99-1.01) or after categorization (12-24 months: HR, 0.75; 95% CI, 0.56-1.02; >24 months: HR, 0.62; 95% CI; 0.47-1.01). There was no evidence of association of the time to recurrence with overall survival, both when analyzed as a continuous variable (HR, 0.99; 95% CI, 0.98-1.02) or after categorization (12-24 months: HR, 0.76; 95% CI, 0.54-1.07; >24 months: HR, 0.61; 95% CI, 0.54-1.03). Those results remained nonsignificant after stratification by treatment.

Conclusions And Relevance: In the MelBase cohort, time to recurrence of metastatic melanoma appears not to be associated with progression-free survival or overall survival.
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http://dx.doi.org/10.1001/jamadermatol.2019.0425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495357PMC
June 2019

Impact of radiotherapy administered simultaneously with systemic treatment in patients with melanoma brain metastases within MelBase, a French multicentric prospective cohort.

Eur J Cancer 2019 05 22;112:38-46. Epub 2019 Mar 22.

APHP Dermatology, Department of Dermatology, Paris 7 Diderot University, INSERM U976, Hôpital Saint-Louis, Paris, France.

Background: Melanoma brain metastases (MBMs) are historically associated with poor prognosis. Radiation therapy is conventionally associated with a high local control rate. Development of targeted therapy and immunotherapy has improved overall survival (OS) and intracranial response rate, but about 50% of patients failed to respond to these novel therapies. The objective of this study was to assess the impact of combined radiotherapy (cRT) on overall survival in a large multicenter real-life prospective cohort of patients with MBM treated with immunotherapy or targeted therapy.

Patients And Methods: Clinical data from 262 patients with MBM were collected via MelBase, a French multicentric biobank prospectively enrolling unresectable stage III or IV melanoma. Two groups were defined: patients receiving cRT (cRT group) or not receiving cRT (no-cRT group). Primary end-point was OS. Propensity score weighting was used to correct for indication bias.

Results: Among the 262 patients, 93 (35%) received cRT (cRT group). The patients were treated with immunotherapy in 69% and 60% and with targeted therapy in 31% and 40% of the cRT and no-cRT groups, respectively. With a median follow-up of 6.9 months, median OS was 16.8 months and 6.9 months in the cRT and no-cRT groups, respectively. After propensity score weighting, cRT was associated with longer OS (hazard ratio = 0.6, 95% confidence interval: 0.4-0.8; p=0.007). Median OS after ponderation was 15.3 months and 6.2 months in the cRT and no-cRT groups, respectively.

Conclusion: This study shows that cRT may be associated with a significant decrease of 40% in the risk of death in patients with MBM treated with systemic therapy.
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http://dx.doi.org/10.1016/j.ejca.2019.02.009DOI Listing
May 2019

Checkpoint blockade after kidney transplantation.

Eur J Cancer 2018 06 26;96:111-114. Epub 2018 Apr 26.

CHU Pontchaillou, Department of Hematology, Rennes, France; INSERM, U1236, Rennes, France. Electronic address:

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http://dx.doi.org/10.1016/j.ejca.2018.03.019DOI Listing
June 2018

STAT3 Mediates Nilotinib Response in KIT-Altered Melanoma: A Phase II Multicenter Trial of the French Skin Cancer Network.

J Invest Dermatol 2018 01 24;138(1):58-67. Epub 2017 Aug 24.

Service de Dermatologie, and CIC (Centre d'Investigations Cliniques), AP-HP, Hôpital Saint-Louis, Paris, France; INSERM, UMR-976, AP-HP, Hôpital Saint-Louis, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France.

Mutated oncogenic KIT is a therapeutic target in melanoma. We conducted a multicenter phase II trial on the KIT inhibitor nilotinib in patients with unresectable melanoma harboring KIT alteration. The primary endpoint was the response rate (complete response or partial response following Response Evaluation Criteria in Solid Tumors criteria) at 6 months. Pharmacodynamic studies using KIT sequencing, qPCR array, and immunostaining of downstream KIT effectors were performed during treatment. Twenty-five patients were included and received 400 mg oral nilotinib twice daily. At 6 months, nilotinib induced tumor response in four patients. The best overall response rate was 20% and the disease control rate was 56%, limited to patients harboring exon 11 or 13 mutations. Four patients exhibited durable response, including three persisting (3.6 and 2.8 years for two patients with stage IIIC and 2.5 years for one with IVM1b melanoma). A reduction in signal transducer and activator of transcription (STAT) 3 phosphorylation and its effectors (BCL-2, MCL-1) in tumors during follow-up was significantly associated with clinical response. In the KIT-mutated melanoma cell line M230, nilotinib reduced STAT3 signaling and STAT inhibitors were as efficient as KIT inhibitors in reducing cell proliferation. Our study evidences a significant association between STAT3 inhibition and response to nilotinib, and provides a rationale for future research assessing STAT inhibitors in KIT-mutated melanoma.
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http://dx.doi.org/10.1016/j.jid.2017.07.839DOI Listing
January 2018

Itch and Pain Characteristics in Skin Carcinomas.

Acta Derm Venereol 2016 06;96(5):697-8

Department of Dermatology, University Hospital, 29200 Brest, France.

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http://dx.doi.org/10.2340/00015555-2316DOI Listing
June 2016

Dual NRASQ61R and BRAFV600E mutation-specific immunohistochemistry completes molecular screening in melanoma samples in a routine practice.

Hum Pathol 2015 Nov 15;46(11):1582-91. Epub 2015 Jul 15.

Service d'Anatomie et Cytologie Pathologiques, CHRU Brest, Brest, F-29220 France; Université Européenne de Bretagne, Brest, F-29200 France; Faculté de Médecine et des Sciences de la Santé, Université de Brest, Brest, F-29200 France. Electronic address:

NRAS and BRAF mutational status has become mandatory to treat patients with metastatic melanomas. Mutation-specific immunohistochemistry (IHC) can help analyze challenging tumor samples. We report our experience integrating NRASQ61R (SP174) and BRAFV600E (VE1) IHC in routine practice in a cancer molecular genetic platform. All samples screened for BRAF and NRAS mutations during the year 2014 were analyzed by IHC and pyrosequencing, with an independent analysis of the 2 methods. Cases with first-line discordant results benefited from a complementary second-round IHC and next-generation sequencing (NGS) with a final interpretation taking into account the results of pyrosequencing, IHC, NGS, and quantification of the tumor cells. We analyzed 111 consecutive formalin-fixed and paraffin-embedded melanoma samples from 101 patients. Twenty-two and 11 samples were concordant for BRAFV600E and NRASQ61R mutations, respectively. Second-round analyses of 9 discordant and 1 molecularly inconclusive samples allowed conclusion in 4 further mutated samples (2 BRAFV600E and 2 NRASQ61R). A sample remained NRASQ61R IHC negative but NRASQ61R mutated with molecular methods. Overall, BRAFV600 and NRASQ61 mutation frequencies were 31.7% and 30.7%, respectively. When compared to molecular results, the sensitivity and specificity of IHC were 100% for BRAFV600E IHC and 92.3% and 98.9% for NRASQ61R IHC, respectively. IHC interpretation required a more stringent cutoff for BRAFV600E IHC than NRASQ61R to minimize false results. We conclude that NRASQ61R and BRAFV600E IHC coupled with NGS allow detection of mutations in melanoma challenging samples.
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http://dx.doi.org/10.1016/j.humpath.2015.06.023DOI Listing
November 2015
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