scholarly journals Melanoma: From Melanocyte to Genetic Alterations and Clinical Options

Scientifica ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-22 ◽  
Author(s):  
Corine Bertolotto
Keyword(s):  
Metastatic Melanoma ◽  
Recent Progress ◽  
Molecular Mechanisms ◽  
Disease Free Survival ◽  
Genetic Alterations ◽  
Cancer Resistance ◽  
Free Survival ◽  
Clinical Responses ◽  
Melanoma Patients ◽  
First Time

Metastatic melanoma remained for decades without any effective treatment and was thus considered as a paradigm of cancer resistance. Recent progress with understanding of the molecular mechanisms underlying melanoma initiation and progression revealed that melanomas are genetically and phenotypically heterogeneous tumors. This recent progress has allowed for the development of treatment able to improve for the first time the overall disease-free survival of metastatic melanoma patients. However, clinical responses are still either too transient or limited to restricted patient subsets. The complete cure of metastatic melanoma therefore remains a challenge in the clinic. This review aims to present the recent knowledge and discoveries of the molecular mechanisms involved in melanoma pathogenesis and their exploitation into clinic that have recently facilitated bench to bedside advances.

Immunogenicity, Including Vitiligo, and Feasibility of Vaccination With AutologousGM-CSF–Transduced Tumor Cells in Metastatic Melanoma Patients

2005 ◽  
Vol 23 (35) ◽  
pp. 8978-8991 ◽  
Author(s):  
Rosalie M. Luiten ◽  
Esther W.M. Kueter ◽  
Wolter Mooi ◽  
Maarten P.W. Gallee ◽  
Elaine M. Rankin ◽  
...  
Keyword(s):  
T Cells ◽  
Metastatic Melanoma ◽  
Tumor Cells ◽  
Disease Free Survival ◽  
High Dose ◽  
Autologous Tumor ◽  
Free Survival ◽  
Gm Csf ◽  
Melanoma Patients ◽  
Disease Free

PurposeTo determine the feasibility, toxicity, and immunologic effects of vaccination with autologous tumor cells retrovirally transduced with the GM-CSF gene, we performed a phase I/II vaccination study in stage IV metastatic melanoma patients.Patients and MethodsSixty-four patients were randomly assigned to receive three vaccinations of high-dose or low-dose tumor cells at 3-week intervals. Tumor cell vaccine preparation succeeded for 56 patients (88%), but because of progressive disease, the well-tolerated vaccination was completed in only 28 patients. We analyzed the priming of T cells against melanoma antigens, MART-1, tyrosinase, gp100, MAGE-A1, and MAGE-A3 using human leukocyte antigen/peptide tetramers and functional assays.ResultsThe high-dose vaccination induced the infiltration of T cells into the tumor tissue. Three of 14 patients receiving the high-dose vaccine showed an increase in MART-1– or gp100-specific T cells in the peripheral blood during vaccination. Six patients experienced disease-free survival for more than 5 years, and two of these patients developed vitiligo at multiple sites after vaccination. MART-1– and gp100-specific T cells were found infiltrating in vitiligo skin. Upon vaccination, the T cells acquired an effector phenotype and produced interferon-γ on specific antigenic stimulation.ConclusionWe conclude that vaccination with GM-CSF–transduced autologous tumor cells has limited toxicity and can enhance T-cell activation against melanocyte differentiation antigens, which can lead to vitiligo. Whether the induction of autoimmune vitiligo may prolong disease-free survival of metastatic melanoma patients who are surgically rendered as having no evidence of disease before vaccination is worthy of further investigation.

Association of HERV-K and LINE-1 hypomethylation with reduced disease-free survival in melanoma patients

Epigenomics ◽  
2020 ◽  
Vol 12 (19) ◽  
pp. 1689-1706
Author(s):  
Maurizio Cardelli ◽  
Remco van Doorn ◽  
Lares Larcher ◽  
Michela Di Donato ◽  
Francesco Piacenza ◽  
...  
Keyword(s):  
Independent Predictor ◽  
Disease Free Survival ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Free Survival ◽  
Melanocytic Lesions ◽  
Long Interspersed Nuclear Elements ◽  
Melanoma Patients ◽  
And Gender ◽  
Disease Free

Aim: To evaluate CpG methylation of long interspersed nuclear elements 1 (LINE-1) and human endogenous retrovirus K (HERV-K) retroelements as potential prognostic biomarkers in cutaneous melanoma. Materials & methods: Methylation of HERV-K and LINE-1 retroelements was assessed in resected melanoma tissues from 82 patients ranging in age from 14 to 88 years. In addition, nevi from eight patients were included for comparison with nonmalignant melanocytic lesions. Results: Methylation levels were lower in melanomas than in nevi. HERV-K and LINE-1 methylation were decreased in melanoma patients with clinical parameters associated with adverse prognosis, while they were independent of age and gender. Hypomethylation of HERV-K (but not LINE-1) was an independent predictor of reduced disease-free survival. Conclusion: HERV-K hypomethylation can be a potential independent biomarker of melanoma recurrence.

Establishing Adrenocortical Carcinoma Specific Prognostic Genes Signature

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S148-S149
Author(s):  
A R Patil ◽  
D S Dabrowski ◽  
J Cotelingam ◽  
D Veillon ◽  
M Ong ◽  
...  
Keyword(s):  
Median Survival ◽  
Poor Prognosis ◽  
Cancer Genomics ◽  
Disease Free Survival ◽  
Genetic Alterations ◽  
Malignant Neoplasms ◽  
Free Survival ◽  
Signature Genes ◽  
Disease Free ◽  
Disease Specific

Abstract Introduction/Objective Adrenal Cortical Carcinoma (ACC) is a rare malignant neoplasms originating from adrenal cortical tissue with an annual incidence rate of 1 to 2 cases per million individuals. These tumors have poor prognosis with 5-year disease free survival being 30% after complete resection in Stage I to Stage III patients. Hence, there is a need for identifying prognostic markers for effective management of disease in these patients. Methods We analyzed the data in The Cancer Genome Atlas of 1141 ACC individuals, using cbioportal.org, a web- based platform for analysis of large-scale cancer genomics data sets, and derived correlation between prognosis and genetic alterations in approximately 51,309 genes. Results We identified 15 signature genes (NOTCH1, TP53, ZNRF3, LRP1, KIF5A, MDM2, LETMD1, MTOR, NOTCH3, RERE, SMARCC2, LDLR, HRNR, AVPR1A and PCDH15), alterations in which indicated a poor prognosis for ACC individuals. Analysis of 15 signature genes demonstrated that disease specific median survival for the patients with ACC, was reduced to 39.5 months (p value < 8 x 10 -9 and sensitivity of 93%) when any one or more of these genes was altered. Whereas, disease specific median survival was greater than 180 months (90% survival being 180 months) with no alteration in our signature genes. In addition, our analysis of our signature genes demonstrates reduced overall survival, disease free survival and progression free survival in individuals having alterations in our signature genes. Moreover, our set of 15 genes belonged mainly to MDM2-TP53, NOTCH and mTOR pathways, and small molecule modulators of these pathways are in process of development. Conclusion Our 15 gene signature was not only able to predict poor prognosis in ACC, but also has the potential to serve as a molecular marker set for initiation of NOTCH and mTOR specific targeted therapies in these patients.

scholarly journals Multimodal genetic features correlate with poor response to neoadjuvant chemoradiotherapy and high recurrence risk in Chinese patients with stage IB-IIA cervical cancer

2020 ◽  
Author(s):  
Yuchun Wei ◽  
Chuqing Wei ◽  
Chen Liang ◽  
Ning Liu ◽  
Zhenhao Fang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Neoadjuvant Therapy ◽  
Disease Free Survival ◽  
Poor Response ◽  
Recurrence Risk ◽  
Genetic Alterations ◽  
Chinese Patients ◽  
Free Survival ◽  
Caucasian Patients ◽  
Disease Free

Abstract Background Response of cervical cancer patients to neoadjuvant therapy differs from person to person. It remains unclear whether genetic alterations can predict response to neoadjuvant therapy and disease-free survival in cervical cancer.Methods 62 Chinese patients with stage IB-IIA cervical cancer were included in this study. Pre-treatment tumor tissues were profiled using a targeted next-generation sequencing assay. Genetic alterations were compared with those identified in the Western populations using the TCGA database. Pathological response and disease-free survival (DFS) were evaluated and their correlations with genetic alterations were analyzed.Results Genetic alterations in PIK3CA were prevalent in both Chinese and Caucasian populations. The mutation frequencies of TERT, POLD1, NOS2, and FGFR3 were significantly higher in Chinese patients whereas RPTOR, EGFR, and TP53 were frequently mutated in Caucasian patients. Germline mutations were identified in 13 out of 62 Chinese patients and 57% of them occurred in DNA repair genes, such as BRCA1/2, TP53 and PALB2. High tumor mutation burden (TMB), TP53 polymorphism (rs1042522) and KEAP1 mutations were found to be associated with poor response to neoadjuvant therapy. KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC amplification and TYMS polymorphism were associated with higher relapse rates of cervical cancer.Conclusion The similarity and difference of mutation landscape of Chinese and Caucasian patients suggested genetic background played a role in shaping the architecture of cervical cancer mutations. The associations of mutation feature of cervical cancer with patient response and tumor recurrence risk provided rationale to further validate and explore potential biomarkers for cervical cancer patients.

scholarly journals Rare Case of Pleomorphic Sarcoma of Oropharynx

2019 ◽  
Vol 05 (02) ◽  
pp. 072-074
Author(s):  
Sajal Goel ◽  
Deepak K. Mittal ◽  
Pankaj Sharma ◽  
Nita Khurana
Keyword(s):  
Locally Advanced ◽  
Adult Life ◽  
Disease Free Survival ◽  
Neck Region ◽  
Head And Neck Region ◽  
Free Survival ◽  
Nonsurgical Management ◽  
Pleomorphic Sarcoma ◽  
First Time ◽  
Disease Free

Abstract Introduction Pleomorphic sarcoma is the commonest soft tissue sarcoma of adult life. Less than 10% cases of this disease occur as primary in head and neck region. Although a case of pleomorphic sarcoma of lower extremity with metastasis to base of tongue had been reported earlier, a pleomorphic sarcoma arising from oropharynx is being reported for the first time. Case Report A 75-year-old male chronic smoker was evaluated for complaints of dysphagia, change in voice, and multiple episodes of oral bleeding. He was found to have a locally advanced pleomorphic sarcoma of oropharynx. He was treated nonsurgically. He showed complete clinical and radiologic response. The disease-free survival is 12 months and overall survival is 74 months. Conclusion This report highlights the importance of nonsurgical management of a case that would have otherwise needed surgery.

scholarly journals Influence of Sentinel Lymph Node Biopsy on Disease-Free Survival for Melanoma Patients

2014 ◽  
Vol 25 ◽  
pp. iv388
Author(s):  
M. Kukushkina ◽  
S. Korovin ◽  
O. Solodiannikova ◽  
G. Sukach ◽  
A. Palivets ◽  
...  
Keyword(s):  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Sentinel Lymph Node Biopsy ◽  
Disease Free Survival ◽  
Lymph Node Biopsy ◽  
Free Survival ◽  
Node Biopsy ◽  
Melanoma Patients ◽  
Disease Free

Presence of VEGF-R3 in the serum of metastatic malignant melanoma patients: Relationship with clinicobiological parameters

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 18004-18004
Author(s):  
R. Mouawad ◽  
J. Meric ◽  
J. Spano ◽  
D. Khayat ◽  
G. Auclerc ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Disease Free Survival ◽  
Metastatic Malignant Melanoma ◽  
Tumor Burden ◽  
Free Survival ◽  
High Tumor Burden ◽  
Healthy Donors ◽  
Melanoma Patients ◽  
And Gender ◽  
Factor C

18004 Background: The presence of metastases is a strong indicator of poor survival in many types of cancer. It has recently been shown that vascular endothelial growth factor-C (VEGF-C), and its receptor Flt-4 (VEGF-R3) are increased in a variety of tumours and may play a pivotal role in the promotion of metastasis. We previously demonstrated that high soluble VEGF-C level was correlated to high tumor burden. Objectives: This study was designed to i) detect and evaluate whether soluble VEGF-R3 play a role in metastatic malignant melanoma patients ii) to determine if they have any relationship with clinicobiological parameters, clinical response and survivals. Methods: Using a sensitive enzyme-linked immunosorbent assays, VEGF-R3 was retrospectively measured in sera of 60 patients with a fully documented history of melanoma disease in comparison with 30 healthy controls. Disease free survival (DFS) and overall survival (OS) were calculated from the beginning of treatment until either the progression (DFS) or death (OS) and analyzed using the Kaplan-Meier method. Results: Pretreatment circulating VEGF-R3 was detectable in all samples from either melanoma patients or healthy donors. Furthermore, median level of sVEGF-R3 was significantly higher (p = 0.000015) in melanoma patients as compared to healthy donors. (38890 vs 30773 pg/ml respectively). No significant association was noted between sVEGF-R3 levels and gender, age or LDH level. Median serum VEGF-R3 level was significantly higher in patients with high tumor burden as compared to patients with low tumor burden (p = 0.045). The pretreatment sVEGF-R3 level was significantly different (p = 0.025) between responder (n = 27) and non-responding patients (n = 33). Lastly, the relapse-free survival was higher in the group with low sVEGF-R3 concentration compared to the high one’s (14.1 vs 11,9 months) as well as for OS (14.3 Vs 12.6 months) but theses differences were not significant (χ2 = 2,30, p = 0.12 & χ2 = 0.74, p = 0.37 respectively). Conclusion: these results suggest that high pretreatment sVEGF-R3 level is related to bad prognosis in melanoma patients. No significant financial relationships to disclose.

Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in metastatic melanoma patients?

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14035-e14035
Author(s):  
Daniele Fanale ◽  
Lorena Incorvaia ◽  
Gaetana Rinaldi ◽  
Lidia Terruso ◽  
Giuseppe Badalamenti ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Primary Tumor ◽  
Primary Melanoma ◽  
Tumor Infiltrating Lymphocytes ◽  
Rank Test ◽  
Expression Levels ◽  
Kaplan Meier ◽  
Melanoma Patients ◽  
Infiltrating Lymphocytes ◽  
First Time

e14035 Background: The immune response to melanoma has been shown to be locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk (infiltrating the entire base of the invasive tumor), non-brisk (infiltrating only focally) and absent. Several studies showed that greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and a higher survival rate. Since recent studies revealed an association between PD-1/PD-L1 expression levels and tumor response, the aim of our study was to investigate the correlation between plasma PD-1 and presence/absence/class of TILs in metastatic melanoma patients. Methods: The plasma PD-1 levels were analyzed in 28 patients with metastatic melanoma using a specific ELISA assay. The characterization of TILs in tumor tissue was performed by immunohistochemistry. Statistical analysis was assessed using t-Student and ANOVA tests. Survival curves were estimated by using the Kaplan-Meier method and log-rank test to evaluate significant differences among them. Results: 16 out of 28 patients showed the presence of TILs in primary tumor, 10 of which brisk and 6 nonbrisk. The plasma PD-1 levels were analyzed in relation to the presence/absence of TILs (p = 0.022), brisk TILs versus nonbrisk/absent TILs (p = 0.014), and brisk vs nonbrisk vs absent TILs (p = 0.032). In particular, low plasma PD-1 levels have been shown to be associated with brisk TILs in primary melanoma, intermediate values with nonbrisk TILs, and high expression with absent TILs. Although the low number of samples did not allow us to obtain a statistically significant association between the plasma PD-1 expression levels and overall survival (OS) depending on the absence or presence of TILs (brisk/nonbrisk), however the median survival of patients having brisk TILs was five months higher than other 2 groups of patients with absent and nonbrisk TILs, respectively. Conclusions: This work highlights, for the first time, the potential ability of using the plasma PD-1 levels to predict prognosis also in patients with metastatic melanoma at diagnosis for which it is not possible to identify the primary tumor.

Patient Preferences for Adjuvant Interferon Alfa-2b Treatment

2001 ◽  
Vol 19 (3) ◽  
pp. 812-823 ◽  
Author(s):  
Kerry L. Kilbridge ◽  
Jane C. Weeks ◽  
Arthur J. Sober ◽  
Frank G. Haluska ◽  
Craig L. Slingluff ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Disease Free Survival ◽  
Interferon Alfa ◽  
Health States ◽  
Free Survival ◽  
Risk Melanoma ◽  
Melanoma Patients ◽  
Disease Free ◽  
Adjuvant Interferon

PURPOSE: Although trials of adjuvant interferon alfa-2b (IFNα-2b) in high-risk melanoma patients suggest improvement in disease-free survival, it is unclear whether treatment offers improvement in overall survival. Widespread use of adjuvant IFNα-2b has been tempered by its significant toxicity. To quantify the trade-offs between IFNα-2b toxicity and survival, we assessed patient utilities for health states associated with IFN therapy. Utilities are measures of preference for a particular health state on a scale of 0 (death) to 1 (perfect health).PATIENTS AND METHODS: We assessed utilities for health states associated with adjuvant IFN among 107 low-risk melanoma patients using the standard gamble technique. Health states described four IFNα-2b toxicity scenarios and the following three posttreatment outcomes: disease-free health and melanoma recurrence (with or without IFNα-2b) leading to cancer death. We also asked patients the improvement in 5-year disease-free survival they would require to tolerate IFN.RESULTS: Utilities for melanoma recurrence with or without IFNα-2b were significantly lower than utilities for all IFNα-2b toxicities but were not significantly different from each other. At least half of the patients were willing to tolerate mild-moderate and severe IFNα-2b toxicity for 4% and 10% improvements, respectively, in 5-year disease-free survival.CONCLUSION: On average, patients rate quality of life with melanoma recurrence much lower than even severe IFNα-2b toxicity. These results suggest that recurrence-free survival is highly valued by patients. The utilities measured in our study can be applied directly to quality-of-life determinations in clinical trials of adjuvant IFNα-2b to measure the net benefit of therapy.

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