Melanoma Research最新文献

The exact role of nevi in the development of melanoma is not yet completely understood, and it remains unknown whether de novo and nevus-associated melanoma (NAM) constitute distinct biological entities. A few studies have documented differences in histological and clinical characteristics between de novo and NAMs; however, data from Southern Europe are lacking. This study examined epidemiological and clinical data of patients who were followed up at the Melanoma Reference Center of the General Hospital of Athens G. Gennimatas from 2022 to 2024 and had been diagnosed with primary skin melanoma from 1999 to 2024. In a total of 509 primary melanomas 289 (56.8%) were nevus-associated and 220 (43.2%) de novo. NAMs were more likely to be diagnosed in patients <40 and 40-65 years old compared to de novo melanomas (P < 0.001). NAMs were more likely to develop on the trunk and the extremities compared to de novo tumors, which predominated on the head (P < 0.001). Superficial spreading melanomas were more likely to be nevus-associated, while nodular, acral lentiginous, and lentigo maligna melanomas were more likely to develop de novo (P < 0.001). NAMs were more likely to be diagnosed at earlier stages and be thinner compared to de novo tumors (P < 0.001). NAMs were also more likely not to present ulceration (P = 0.002) and to have a low mitotic rate (<3/mm2) (P < 0.001). Patients with de novo melanomas more often experienced disease progression compared to those with NAM. NAMs seem to have less aggressive behavior compared to de novo melanomas. This study highlights the differences between de novo and NAMs, adding novel information about features such as the presence of dysplastic nevi, the mitotic rate, and the disease progression that had not been investigated in previous studies.

This retrospective cohort study evaluated disparities across insurance types, racial groups, and socioeconomic status (SES) in acral lentiginous melanoma (ALM). We analyzed adults diagnosed with ALM in the National Cancer Database from 2016-2020. Cox proportional hazards model assessed associations between demographic and clinical variables with ALM-specific survival. Kaplan-Meier curves analyzed 1-, 3-, and 5-year survival. A total of 3446 patients with ALM were identified. Uninsured patients presented with advanced-stage cancers, experienced longer time to treatment, and were more likely to undergo major amputations compared with privately insured patients ( P  < 0.001). Survival analysis indicated lower probabilities for uninsured patients at 1, 3, and 5 years, although the differences did not reach statistical significance. Black patients were more likely uninsured, had higher Charlson-Deyo comorbidity scores, resided in areas of lower income and education, experienced longer time to treatment ( P  < 0.001), and had significantly lower survival at 3 and 5 years compared with White patients ( P  < 0.01). Patients in SES Q1 traveled further for care, had longer time to treatment, were less likely to be treated with Mohs surgery ( P  < 0.001), and had worse survival at 1, 3, and 5 years compared with patients in SES Q4 ( P  < 0.001). In conclusion, significant disparities in disease presentation, access to care, and health outcomes in patients with ALM exist based on insurance status, race, and SES, emphasizing the need for targeted interventions to enhance early diagnosis and equitable treatment.

Pathogenic variants in the CDKN2A gene are the most common genetic cause of hereditary melanoma, significantly increasing the risk of multiple melanomas at an early age and the incidence of noncutaneous tumors, particularly pancreatic cancer. Similarly, the MITF p.E318K variant is associated with an elevated risk of cutaneous melanoma, renal cell carcinoma, and pancreatic cancer. This study investigates the incidence of cutaneous and noncutaneous cancers among first- and second-degree relatives of patients with cutaneous melanoma who carry the same CDKN2A or MITF p.E318K germline variants as their corresponding index case. Among 62 relatives of patients with cutaneous melanoma, 48 (77.4%) carried CDKN2A variants, while 14 (22.6%) carried the MITF p.E318K variant. Of the 39 CDKN2A carriers with follow-up data (mean duration: 60.87 months), 31 were cancer-free at the time of genetic diagnosis, while eight had a prior cancer history, including seven with cutaneous melanoma. During follow-up, five carriers developed a new cancer. In CDKN2A families, additional cutaneous melanoma and pancreatic cancer cases were observed in 43.75 and 21.87% families, respectively. In the MITF cohort, none of the 12 cancer-free carriers developed cutaneous melanoma during a mean follow-up of 24.64 months, although two developed basal cell carcinoma. Among the three index cases, two had invasive cutaneous melanoma, and all three families had pancreatic cancer cases. This study highlights the heightened elevated cancer risk for CDKN2A and MITF p.E318K variant emphasizing the need for ongoing surveillance.

Compound 48/80 (Com 48/80), a mast cell degranulator, triggers allergic reactions and has been linked to a reduced risk of skin cancer. This study investigated the potential anticancer effects of Com 48/80 using in vitro and in vivo melanoma models. In vitro, Com 48/80 significantly induced apoptosis in melanocytes through caspase activation. In the melanoma animal model experiment, Com 48/80 enhanced survival, reduced tumor volume, and downregulated melanoma-specific genes (Dct2 and Gp100), while increasing the activities of caspase-3, -8, and -9. Additionally, Com 48/80 elevated allergy-related and immune-enhancing mediators, including immunoglobulin E, histamine, interleukin (IL)-2, IL-4, IL-5, IL-6, IL-12, IL-13, IL-33, tumor necrosis factor-α, thymic stromal lymphopoietin, and interferon-γ. In the immunodeficient mice, Com 48/80 improved survival, suppressed melanoma growth, reduced immobility time, and enhanced the expression of immune mediators. Moreover, Com 48/80 significantly lowered tissue damage indicators compared to tumor control mice. These results suggest that Com 48/80 inhibits melanoma progression by inducing apoptosis and enhancing immune responses, highlighting the potential of Com 48/80 as a novel therapeutic strategy for melanoma treatment and prevention.

Metastatic melanoma is characterized by high rates of treatment resistance. While various factors have been studied for their prognostic significance, this study evaluated the potential prognostic value of the intrinsic disorder of T-cell receptor beta (TRB) polypeptides. TRB recombination sequencing reads were extracted from tumor RNA-seq files representing The Cancer Genome Atlas, Skin Cutaneous Melanoma dataset, and genomics files representing the National Institutes of Health, phs002683 dataset. Intrinsic disorder values were computed for the TRB V-complementarity determining region 3 (CDR3)-J amino acid sequences for all cases. Survival analyses assessed overall survival and disease-specific survival for case sets based on assigning cases to upper or lower 50 th percentile groups, based in turn on intrinsic disorder values. For the phs002683 dataset, intrinsic disorder values were compared between cases representing resistance to immune checkpoint inhibitors (ICIs) and cases representing no observed resistance. The results indicated that the upper 50 th percentile of the range of intrinsic disorder values was linked to better outcomes. This was obtained for two TRB datasets representing different RNA-seq file, recombination read extraction algorithms, and was observed for two different intrinsic disorder models. Furthermore, low minimum various long-3 and various short-long 2 values correlated with ICI treatment resistance. The findings of this study suggest that the diversity of intrinsic disorder values representing TRB V-CDR3-J assemblies may represent a novel prognostic biomarker for metastatic melanoma cases and a potential biomarker for indicating different personalized treatments.

Patients with mucosal melanoma have lower survival rates than those with cutaneous melanoma. Recent studies have reported lower mucosal melanoma survival rates with the use of immune checkpoint inhibitors (ICIs). This study analyzed ICI treatment outcomes in patients with mucosal melanoma in a real-world context. The objective response rate, progression-free survival (PFS), and overall survival (OS) after first- and second-line ICI treatments were analyzed in a population of patients with advanced mucosal melanoma included in the observational GEM1801 study in Spain. Univariate Cox regression analysis was used to identify prognostic factors. From 1126 patients included between August 2018 and January 2024, 52 (4.6%) patients with mucosal melanoma were selected, with a median age at advanced stage diagnosis of 70 years; 50% were female. Most patients had an Eastern Cooperative Oncology Group performance status of 0 (48%). Tumors were primarily located in the lower gastrointestinal tract (40%) and the nasal cavity (35%). In the metastatic setting, 32 (62%) patients received ICI. At a median follow-up of 13.7 months, patients receiving ICI had a median PFS and OS of 9.4 [95% confidence interval (CI): 6.6-17.0] and 25.9 (95% CI: 21-not reached) months, respectively, for first-line treatment, and 5.1 (95% CI: 1.9-not reached) and 21.0 (95% CI: 11.1-not reached) months for second-line treatment. The clinical benefit of ICI treatment in mucosal melanoma is in accordance with previous clinical trials but is still limited, highlighting the need for new approaches for this patient population.

Prognosis for metastatic melanoma patients treated with immune checkpoint inhibitors (ICIs) remains heterogeneous. Although neutrophil-to-lymphocyte ratio (NLR) and neutrophil-to-eosinophil ratio (NER) are established markers, we hypothesized a neutrophil-to-lymphocyte-times-eosinophil (NLE) index would offer superior stratification. We analyzed 194 metastatic melanoma patients receiving ICIs, divided into training ( n  = 129) and validation ( n  = 65) cohorts. An optimal NLE cutoff categorized patients as NLE-low or NLE-high. Survival outcomes and objective response rate (ORR) were assessed using Kaplan-Meier, Cox regression, and logistic regression. Predictive accuracy of NLE, NLR, and NER was compared. Median overall survival was significantly longer in NLE-low versus NLE-high patients (training: 31.3 versus 6.9 months; P  = 0.011; validation: 33.5 versus 9.1 months; P  = 0.019). Median progression-free survival also improved significantly in NLE-low patients (training: 10.6 versus 3.1 months; P  = 0.029; validation: 13.7 versus 3.9 months; P  = 0.012). ORR was higher in NLE-low groups (training: 46.0% versus 13.2%; P  < 0.001; validation: 43.6% versus 18.2%; P  = 0.078). NLE demonstrated superior predictive accuracy compared with NLR and NER. The NLE index outperforms NLR and NER in predicting survival and response in metastatic melanoma patients treated with ICIs, providing a practical clinical tool.

Peritoneal carcinomatosis represents an exceptionally rare metastatic pattern of cutaneous malignant melanoma, occurring in fewer than 1% of cases with distant spread and typically within the first few years after primary treatment. This report presents an unusual case with a markedly prolonged disease-free interval, clinically mimicking advanced ovarian carcinoma. We report the case of a 53-year-old woman treated more than 10 years ago for stage IIB nodular melanoma with surgery and adjuvant therapy. The patient presented with progressive abdominal bloating. Imaging revealed bilateral adnexal masses, ascites, peritoneal carcinomatosis, and multiple pulmonary nodules, initially suggestive of advanced ovarian cancer. Diagnostic laparoscopy demonstrated diffuse peritoneal lesions with an atypical yellowish, soft, and nonpigmented appearance. Histology and immunohistochemistry confirmed metastatic melanoma. This case is among the few reports of peritoneal carcinomatosis from melanoma after more than a decade of remission. The prolonged disease-free interval and atypical presentation underline the heterogeneous behavior of melanoma and the need for long-term vigilance and multidisciplinary evaluation.

Wide local excision (WLE) is the standing surgical choice for acral lentiginous melanoma (ALM), yet research is scarce in evaluating other surgical options for ALM and its recurrence rates remain two to five times more likely than other melanoma subtypes. This study evaluates the overall survival outcomes associated with different surgical modalities in patients with stage 0-II ALM. This retrospective cohort study surveyed the National Cancer Database from 2004 to 2021 for International Classification of Diseases-10 codes specific for all skin structures with histologically confirmed ALM for stage 0-II patients. Using IBM SPSS, statistical analyses were conducted via variable frequency with crosstabulations and Chi-squared tests, Kaplan-Meier survival curves with log-rank pairwise comparisons, and Cox proportional hazards regression models. Data for 6737 patients showed significantly greater overall survival for biopsy followed by gross excision (BFGE) than WLE [median overall survival = 204.8 months ( P  < 0.001); hazard ratio = 0.77 (95% confidence interval, 0.68-0.87)]. Median overall survival for WLE was 181.6 months. Cross analysis of Breslow depth (BD) with surgical procedures revealed the majority (21.8%) of WLEs were completed for lesions with a BD of 0.1-5 mm followed by 16.8% for lesions greater than 3 cm ( P  < 0.001). Crossanalysis of surgical margins of the primary site with surgical procedures, showed no residual tumor in 92.1% of all BFGE patients, which is 3.7% and 3.3% less patients than major amputation and WLE. This study highlights significant differences across ALM surgery options, suggesting each modality has their own niche and BFGE should be investigated further.

The surfactant protein-C (SFTPC) gene encodes a hydrophobic pulmonary surfactant protein essential for lung function and homeostasis. While primarily associated with lung diseases, emerging evidence suggests its potential involvement in human cancers. In addition, SFTPC expression was also found in human skin cells, however, its expression profile in cutaneous melanoma is unknown. In this study, we analyzed expression profiles of SFTP family genes including SFTPA1/2 , SFTPB , SFTPC , and SFTPD in human skin melanoma tissues. Our analysis revealed that SFTPC expression was the predominant SFTP gene and was associated with disease progression, including tumor stage, Clark level, and Breslow depth. High levels of SFTPC expression in skin melanoma tissues were significantly associated with patient survival outcomes including overall and disease-specific survival. The associations were specifically dictated in aggressive tumors, suggesting a potential role of SFTPC expression in melanoma progression. Interestingly, SFTPC expression was negatively correlated with T-helper cell infiltration in skin melanoma tissues. Gene enrichment analysis also indicated that SFTPC expression was in parallel with elevated expressions of mitochondrial energy biosynthesis-related genes and reduced IgE/IgG-mediated immunity-related genes. In conclusion, SFTPC upregulation is associated with disease progression and patient survival outcomes, possibly through enhancing ATP overproduction and suppressing antitumor immunity.