Melanoma Research最新文献

{"title":"Patterns of expression and prognostic implication of glycoprotein nonmetastatic protein B (GPNMB) expression in sentinel lymph nodes of melanoma patients.","authors":"Ariel Beitner, Adam Abu-Abeid, Danit Dayan, Andrea Gat, Mor Miodovnik, Carmit Levy, Eran Nizri","doi":"10.1097/CMR.0000000000001019","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001019","url":null,"abstract":"<p><p>Sentinel lymph node biopsy (SLNB) is a critical procedure in the management of melanoma, offering prognostic information and guiding adjuvant therapy. Glycoprotein nonmetastatic melanoma protein B (GPNMB), a melanogenesis marker, has been implicated in melanoma progression. This study investigates the expression patterns of GPNMB in SLN metastases and their association with oncological outcomes. We conducted a retrospective analysis of 27 melanoma patients with positive SLNB at Tel Aviv Sourasky Medical Center between 2010 and 2020. Immunohistochemistry was used to assess GPNMB expression in SLN metastases, categorizing patients into two groups based on GPNMB expression patterns: homogeneous (GPNMBho) and margin high (GPNMBmh). Peri-tumoral CD8+ T cell infiltration was also evaluated. Clinical outcomes, including melanoma-specific survival (MSS) and disease-free survival (DFS), were analyzed. GPNMB expression in SLN metastases displayed two distinct patterns: uniform (GPNMBho) and high at the tumor margins (GPNMBmh). Patients in the GPNMBmh group had significantly more peri-tumoral CD8+ T cells and exhibited improved MSS (127.6, 95% CI: 111.7-143.5 vs 79.5, 95% CI: 48.2-110.9 months, P = 0.018) and DFS (107.5, 95% CI: 79-135.8 vs 38, 95% CI: 15.2-60.8 months, P = 0.04) compared to the GPNMBho group. Multivariate analysis confirmed that GPNMB expression pattern and lymph node metastasis size were independent predictors of both MSS and DFS. GPNMB expression patterns in SLN metastases are strongly associated with long-term oncological outcomes in melanoma patients. The GPNMBmh pattern, characterized by higher margin expression and increased CD8+ infiltration, may serve as a prognostic biomarker for recurrence if validated in larger cohorts.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MHC class II: a predictor of outcome in melanoma treated with immune checkpoint inhibitors.","authors":"Karim Amrane, Pierre Le Noac'h, Patrice Hemon, Ronan Abgral, Coline Le Meur, Olivier Pradier, Laurent Misery, Delphine Legoupil, Christian Berthou, Arnaud Uguen","doi":"10.1097/CMR.0000000000001022","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001022","url":null,"abstract":"<p><p>This study aimed to evaluate the predictive value of MHC class II (MHC-II) expression by melanoma cells in a large cohort of metastatic cutaneous melanoma patients treated with immune checkpoint inhibitors (ICIs). We conducted a single-center, retrospective study involving stage IV cutaneous melanoma patients who received ICI as first-line therapy. MHC-II expression in melanoma cells was quantified using dual-color anti-SOX10 and anti-MHC-II immunohistochemistry on tumor samples from 95 patients. The primary endpoint was event-free survival (EFS), with secondary endpoints including 1-year EFS, 1-year overall survival (OS), disease control rate (DCR), and the correlation between MHC-II expression and clinico-biological characteristics. The cohort had a median age of 67 years (range, 33-90), with a male-to-female ratio of 50 : 45. Thirty-three percent of patients received the ipilimumab-nivolumab combination. The median follow-up was 16.8 months. Disease progression occurred in 58 patients (61%), with a median time to progression of 4.8 months. Forty-six patients (48.4%) experienced an event within the first year, and 52 patients (54.7%) died during follow-up. MHC-II positivity was observed in ≥10% of melanoma cells in 6.3% of patients. MHC-II expression was significantly associated with 1-year EFS (P = 0.037) and DCR (P = 0.032), but not with EFS or 1-year OS. Age, phototype, and brain metastases were correlated with MHC-II expression status. Our findings suggest that MHC-II expression by melanoma cells may serve as a favorable predictive biomarker for survival in metastatic cutaneous melanoma patients treated with ICIs.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relation between dabrafenib plus trametinib-induced pyrexia and age in BRAF V600-mutated metastatic melanoma patients: A post hoc analysis of the real-world ELDERLYMEL study.","authors":"Inés González-Barrallo, Victoria Eugenia Castellón Rubio, Javier Medina, Sofia España Fernández, Karmele Mujika, Margarita Majem, Carlos Aguado, Miguel Ángel Cabrera Suárez, Isabel Palacio, Lisa Osterloh, Alejandro Martínez-Fernández, Almudena García-Castaño","doi":"10.1097/CMR.0000000000001020","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001020","url":null,"abstract":"<p><p>Pyrexia is the most common adverse event in patients treated with dabrafenib plus trametinib. However, the pathogenesis of pyrexia and factors to identify patients at higher risk of developing pyrexia remain unknown. The ELDERLYMEL study was a multicenter, noninterventional, retrospective, real-world study comparing the effectiveness and safety of dabrafenib plus trametinib between elderly (≥75 years, n = 29) and younger (<75 years, n = 130) advanced melanoma BRAF V600-mutated patients in Spain. Surprisingly, pyrexia was significantly less frequent in elderly patients (13.8%) than in younger (42.3%). The post hoc analysis presented here aimed to investigate the relationship between age and pyrexia, applying logistic regression models. Patients <75 years had 4.59 more possibilities to develop pyrexia than elderly patients. The possibility of developing pyrexia increased by 1.03 as age decreased by 1 year. Receiver operating characteristics curves identified 61.5 years as the optimal cutoff value to predict the onset of pyrexia. The age-adjusted regression model revealed that patients <61.5 years had 2.53 more possibilities to develop pyrexia than those ≥61.5. This study demonstrates, for the first time, that age significantly influences the development of pyrexia in patients with BRAF V600-mutated advanced melanoma receiving dabrafenib plus trametinib. Age should be considered in the management and follow-up of these patients but should not limit treatment decisions. These findings provide important insights for clinical practice and contribute to a better understanding of pyrexia in elderly patients. The constructed nomogram based on age could serve as a useful tool for estimating the risk of pyrexia in patients receiving this treatment.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic concordance in melanoma: insights from primary tumors and their matched distant metastases.","authors":"Thamila Kerkour, Ruud W J Meijers, Loes M Hollestein, Anne M L Jansen, Ayla Haanappel, Peggy Atmodimedjo, Willeke A M Blokx, Bas van Brakel, Tamar E C Nijsten, Antien L Mooyaart","doi":"10.1097/CMR.0000000000001024","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001024","url":null,"abstract":"<p><p>Melanoma metastasis poses a significant challenge due to its aggressive nature and increasing incidence. Confirming the clonal relationship between the primary melanoma and its metastasis is essential to developing reliable prediction models. Here, we compared the genetic profile of primary melanoma and matched metastasis to assess their genetic clonal relationship. Using a targeted sequencing panel encompassing 330 amplicons, we targeted hotspot regions in 41 cancer genes and 154 single nucleotide polymorphisms. The clonal relation between primary and matched metastasis tumors was evaluated by comparing the mutational status and the copy number variations profile in 15 patients with primarily thin melanomas and distant metastases, or with a long latency between the primary melanoma and distant metastasis. Our findings revealed that only about 50% of the analyzed matched primaries and metastases were clonally or likely clonally related, while the remaining sets were either not clonally related or difficult to determine with certainty the clonal relatedness. The findings of our study illustrate the intricate clonal relationships between primary melanoma and metastasis and raise doubts if the metastatic potential is overestimated in the primary tumors. Further investigation with larger cohorts is needed to better understand this complexity of melanoma metastasis and clonality phenomenon, which should be carefully considered when using primary tumor molecular profiles for prognostic model building or therapeutic guidance in metastatic cases.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain metastases during follow-up of patients with resected cutaneous melanoma.","authors":"Faruk Tas, Kayhan Erturk","doi":"10.1097/CMR.0000000000001026","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001026","url":null,"abstract":"<p><p>Melanoma is among the most common tumors that disseminate to the brain. We analyzed patients with resected early-stage cutaneous melanoma who developed sole brain metastases and brain metastases accompanying other organ spreads and interpreted the clinical characteristics of these patients in this study. A total of 457 patients who developed any organ metastases during or after adjuvant therapy or in follow-up were included in the analysis. A total of 55 (12%) patients had brain metastases (M1d), and 402 patients had other (M1a,b,c) metastases. The majority of brain metastases (n = 36, 65.4%) were accompanied by other organ metastases, only 19 patients had sole brain metastases. Brain metastases were mostly in men (76.4 vs. 61.9%, P = 0.03), and extracerebral dissemination was more commonly associated with acral lentiginous melanoma histopathology (16.7 vs. 4.7%, P = 0.04). Brain metastasis was found to be associated with shorter survival (median survivals were 6.0 vs. 12.45 months, respectively, P = 0.0001). However, there was no difference in survival between patients with isolated brain involvements and patients with brain metastases accompanied by spread to other organs (median survivals were 6.0 vs. 5.85 months, respectively, P = 0.1). In conclusion, brain metastases are a very small portion of relapsed melanoma patients, and the numbers of isolated brain metastases are even smaller, thus the significance of routine brain scans for early detection of brain involvement in the follow-up of patients might be questionable and unnecessary.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis and management of concurrent metastatic melanoma and chronic myelomonocytic leukemia.","authors":"Kishan A Bhatt, Anna J Vaynrub, Jason Cham, Sunil G Iyer, Benjamin Izar","doi":"10.1097/CMR.0000000000001025","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001025","url":null,"abstract":"<p><p>While the association between chronic lymphocytic leukemia (CLL) and a higher incidence of melanoma is well documented, the diagnosis of concurrent high-risk chronic myelomonocytic leukemia (CMML) and metastatic melanoma (MM) has not previously been described. Moreover, the treatment of MM and CMML differ greatly in the mechanism of action of their corresponding antineoplastic therapies: treatment of MM frequently involves immune checkpoint inhibitors (ICI), while patients with CMML receive myelosuppressive agents. Simultaneous management of these malignancies can be nuanced due to the potential impact of one treatment's constituents on the activity of the other and the broad and nonoverlapping array of potential adverse effects of these agents. Here, we describe the clinical course of a patient who was diagnosed with concurrent MM and CMML and our approach to the challenging balance of delivering ICI concurrently with the hypomethylating agent azacitidine and the BCL-2 inhibitor venetoclax.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"International incidence of melanoma in heart transplant recipients: a meta-analysis.","authors":"Paola Campillo, Alice Kesler, Camila A Ramírez, Carlos J Ramírez, Jean Carlo Daher, Mason Grimm, Michael Sabina, Anas Bizanti","doi":"10.1097/CMR.0000000000001008","DOIUrl":"10.1097/CMR.0000000000001008","url":null,"abstract":"<p><p>The incidence of heart transplants in the USA has increased by 85.8% since 2011, resulting in a growing population of recipients requiring long-term immunosuppressive therapy. While essential for preventing organ rejection, this therapy significantly increases melanoma risk. This meta-analysis investigates the incidence and risk factors of melanoma in heart transplant recipients. A systematic review and meta-analysis were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, including observational studies reporting melanoma incidence in heart transplant recipients. Relative risk (RR) was synthesized from standardized incidence ratios, hazard ratios, incidence rate ratios, and standardized mortality ratios. The meta-analysis incorporated 10 studies, including 22 415 heart transplant recipients. The pooled RR was 2.21 (95% confidence interval: 1.32-3.71; P  = 0.003), indicating a significantly elevated melanoma risk. This study highlights the critical need for preventive dermatological strategies in heart transplant recipients and calls for further research into the impact of different immunosuppressive regimens on melanoma risk. Despite limitations, these findings offer valuable insights for optimizing long-term patient care.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"24-30"},"PeriodicalIF":1.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expect the unexpected: a saying to bear in mind.","authors":"Ji Fung Yong, Claire Quigley, Li Jie Helena Yoo, Maureen Connolly, Anne-Marie Tobin","doi":"10.1097/CMR.0000000000001009","DOIUrl":"10.1097/CMR.0000000000001009","url":null,"abstract":"","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":"35 1","pages":"75-76"},"PeriodicalIF":1.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-life effectiveness on overall survival of continued immune checkpoint inhibition following progression in advanced melanoma: estimation from the Melbase cohort.","authors":"Camille Macaire, Wendy Lefevre, Sophie Dalac, Henri Montaudié, Delphine Legoupil, Olivier Dereure, Caroline Dutriaux, Marie Thérèse Leccia, François Aubin, Jean Jacques Grob, Philippe Saiag, Julie De Quatrebarbes, Eve Maubec, Thierry Lesimple, Florence Granel-Brocard, Laurent Mortier, Stéphane Dalle, Céleste Lebbé, Chloé Prod'homme","doi":"10.1097/CMR.0000000000000973","DOIUrl":"10.1097/CMR.0000000000000973","url":null,"abstract":"<p><p>The link between palliative care and oncology must continue to develop, taking into account advances in treatment.Immune checkpoint inhibition (ICI) for metastatic melanoma is associated with different types of response, making it difficult to assess the benefits to the patient. Some clinical trials suggest a survival advantage of ICI even in the absence of an objective radiographic response. The aim of this study is to assess the impact of continuing ICI after progression of the disease on the overall survival (OS) in a cohort of final-line metastatic melanoma patients. Clinical data from 120 patients with metastatic melanoma were collected via Melbase, a French multicentric biobank, prospectively enrolling unresectable melanoma. Two groups were defined: patients continuing final-line ICI at progression (treated) and patients stopping ICI at progression (controls). The primary end-point is the OS from progression. Propensity score weighting was used to correct for indication bias. From the 120 patients, 72 (60%) continued ICI. Median OS from progression was 4.2 months [95% confidence interval (CI) 2.6-6.27] in the treated group and median OS was 1.3 months (95% CI 0.95-1.74) in the control group ( P  < 0.0001). The calculated hazard ratio was 0.20 (0.13-0.33). Continued ICI was discovered to have an association with a higher rate of hospitalization at the end of life; more treatments received in the last 15 days of life and less utilization of specialist palliative care. This study discovered that patients with metastatic melanoma show a significant decrease in the instantaneous probability of mortality when they continue with finale-line ICI after progression.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"50-59"},"PeriodicalIF":1.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATF3 regulates CDC42 transcription and influences cytoskeleton remodeling, thus inhibiting the proliferation, migration and invasion of malignant skin melanoma cells.","authors":"Liang Niu, Shuo Liu, Jiuxiao Shen, Jin Chang, Xiaojing Li, Ling Zhang","doi":"10.1097/CMR.0000000000001011","DOIUrl":"10.1097/CMR.0000000000001011","url":null,"abstract":"<p><p>Cutaneous malignant melanoma (CMM) is one of the most aggressive and lethal types of skin cancer. Cytoskeletal remodeling is a key factor in the progression of CMM. Previous research has shown that activating transcription factor 3 (ATF3) inhibits metastasis in bladder cancer by regulating actin cytoskeleton remodeling through gelsolin. However, whether ATF3 plays a similar role in cytoskeletal remodeling in CMM cells remains unknown. Various gene and protein expression analyses were performed using techniques such as reverse transcription quantitative PCR, western blot, immunofluorescent staining, and immunohistochemical staining. CMM viability, migration, and invasion were examined through cell counting kit-8 and transwell assays. The interactions between cell division cycle 42 (CDC42) and ATF3 were investigated using chromatin immunoprecipitation and dual-luciferase reporter assays. CDC42 was upregulated in CMM tissues and cells. Cytoskeletal remodeling of CMM cells, as well as CMM cell proliferation, migration, and invasion, were inhibited by CDC42 or ATF3. ATF3 targeted the CDC42 promoter region to regulate its transcriptional activity. ATF3 suppresses cytoskeletal remodeling in CMM cells, thereby inhibiting CMM progression and metastasis through CDC42. This research may provide a foundation for using ATF3 as a therapeutic target for CMM.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"37-49"},"PeriodicalIF":1.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142730347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}