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International Journal of Molecular... Jan 2024Preferentially Expressed Antigen in Melanoma (PRAME), a member of the cancer/testis antigen family, is central to the field of skin cancer diagnostics and therapeutics.... (Review)
Review
Preferentially Expressed Antigen in Melanoma (PRAME), a member of the cancer/testis antigen family, is central to the field of skin cancer diagnostics and therapeutics. As a nuclear receptor and transcriptional regulator, PRAME plays a critical role in inhibiting retinoic acid signalling, which is essential for cell differentiation and proliferation. Its aberrant overexpression in various malignancies, particularly cutaneous melanoma, is associated with more aggressive tumour phenotypes, positioning PRAME as both a diagnostic and prognostic marker. In melanoma, PRAME is typically highly expressed, in contrast to its weak or absent expression in benign nevi, thereby improving the accuracy of differential diagnoses. The diagnostic value of PRAME extends to various lesions. It is significantly expressed in uveal melanoma, correlating to an increased risk of metastasis. In acral melanomas, especially those with histopathological ambiguity, PRAME helps to improve diagnostic accuracy. However, its expression in spitzoid and ungual melanocytic lesions is inconsistent and requires a comprehensive approach for an accurate assessment. In soft tissue sarcomas, PRAME may be particularly helpful in differentiating melanoma from clear cell sarcoma, an important distinction due to their similar histological appearance but different treatment approaches and prognosis, or in detecting dedifferentiated and undifferentiated melanomas. In non-melanoma skin cancers such as basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma, the variable expression of PRAME can lead to diagnostic complexity. Despite these challenges, the potential of PRAME as a therapeutic target in melanoma is significant. Emerging immunotherapies, including T-cell-based therapies and vaccines targeting PRAME, are being investigated to exploit its cancer-specific expression. Ongoing research into the molecular role and mechanism of action of PRAME in skin cancer continues to open new avenues in both diagnostics and therapeutics, with the potential to transform the management of melanoma and related skin cancers.
Topics: Humans; Male; Antigens, Neoplasm; Biomarkers, Tumor; Diagnosis, Differential; Melanocytes; Melanoma; Prognosis; Skin Neoplasms; Transcription Factors
PubMed: 38338862
DOI: 10.3390/ijms25031582 -
International Journal of Dermatology May 2020Integrins are the major family of cell adhesion receptors in humans and essential for a wide range of normal physiology, including formation and maintenance of tissue... (Review)
Review
Integrins are the major family of cell adhesion receptors in humans and essential for a wide range of normal physiology, including formation and maintenance of tissue structure integrity, cell migration, proliferation, and differentiation. Integrins also play a prominent role in tumor growth and metastasis. Translational research has tried to define the contribution of integrins to the phenotypic aggressiveness of melanoma because such knowledge is clinically useful. For example, differential expression of integrins in primary cutaneous melanoma can be used to distinguish indolent from aggressive, prometastatic melanoma. Recent studies have shown that gene expression-based testing of patient-derived melanoma tissue is feasible, and molecular tests may fully replace interventional surgical methods such as sentinel lymph node biopsies in the future. Because of their central role in mediating invasion and metastasis, integrins are likely to be useful biomarkers. Integrins are also attractive candidate targets for interventional therapy. This article focuses on the role of integrins in melanoma and highlights recent advances in the field of translational research.
Topics: Biomarkers, Tumor; Cell Adhesion; Diagnosis, Differential; Disease-Free Survival; Feasibility Studies; Humans; Integrins; Melanoma; Neoplasm Invasiveness; Predictive Value of Tests; Prognosis; Sentinel Lymph Node Biopsy; Skin; Skin Neoplasms
PubMed: 32157692
DOI: 10.1111/ijd.14850 -
Cancer Mar 2020Melanoma is among the few cancers that demonstrate an increasing incidence over time. Simultaneously, this trend has been marked by an epidemiologic shift to earlier... (Review)
Review
Melanoma is among the few cancers that demonstrate an increasing incidence over time. Simultaneously, this trend has been marked by an epidemiologic shift to earlier stage at diagnosis. Before 2011, treatment options were limited for patients with metastatic disease, and the median overall survival was less than 1 year. Since then, the field of melanoma therapeutics has undergone major changes. The use of anti-CTLA-4 and anti-PD1 immune checkpoint inhibitors and combination BRAF/MEK inhibitors for patients with BRAF V600 mutations has significantly extended survival and allowed some patients to remain in durable disease remission off therapy. It has now been confirmed that these classes of agents have a benefit for patients with stage III melanoma after surgical resection, and anti-PD1 and BRAF/MEK inhibitors are standards of care in this setting. Some patients with stage II disease (lymph node-negative; American Joint Committee on Cancer stage IIB and IIC) have worse melanoma-specific survival relative to some patients with stage III disease. Given these results, expanding the population of patients who are considered for adjuvant therapy to include those with stage II melanoma has become a priority, and randomized phase 3 clinical trials are underway. Moving into the future, the validation of patient risk-stratification and treatment-benefit prediction models will be important to improve the number needed to treat and limit exposure to toxicity in the large population of patients with early stage melanoma.
Topics: Antineoplastic Agents; Antineoplastic Agents, Immunological; Chemotherapy, Adjuvant; Humans; Immunotherapy; Interferons; MAP Kinase Kinase 1; Medical Illustration; Melanoma; Neoplasm Recurrence, Local; Neoplasm Staging; Numbers Needed To Treat; Programmed Cell Death 1 Receptor; Proto-Oncogene Proteins B-raf; Risk Assessment; Skin Neoplasms
PubMed: 31869447
DOI: 10.1002/cncr.32585 -
BMJ Case Reports Mar 2022Eccrine porocarcinoma is a rare skin adnexal malignant neoplasm that may arise from a pre-existing benign eccrine poroma or without a predisposing factor. It is a highly...
Eccrine porocarcinoma is a rare skin adnexal malignant neoplasm that may arise from a pre-existing benign eccrine poroma or without a predisposing factor. It is a highly invasive neoplasm and has a strong metastatic potential. The most frequently affected organs are the lymph nodes and rarely solid organs such as the liver, lungs and breast. We report a case of a woman with a history of surgically treated eccrine porocarcinoma that a year later presented with multiple lesions in both breasts and axillary lymphadenopathies. After a detailed imaging investigation, the diagnosis of metastatic lesions from porocarcinoma was made. To our knowledge, until the moment, only one case of breast metastasis of eccrine porocarcinoma has been reported in the literature.
Topics: Eccrine Porocarcinoma; Female; Humans; Melanoma; Poroma; Skin Neoplasms; Sweat Gland Neoplasms
PubMed: 35256370
DOI: 10.1136/bcr-2021-247900 -
Revista Do Colegio Brasileiro de... 2020This study evaluates melanoma characteristics in the elderly.
OBJECTIVE
This study evaluates melanoma characteristics in the elderly.
METHODS
A retrospective descriptive analytical study was carried out by reviewing the medical records of patients aged 60 years or older, diagnosed with primary cutaneous melanoma, and treated at Hospital Erasto Gaertner, Curitiba, Paraná, from 2013 to 2017.
RESULTS
We studied 139 patients aged 60-98 years (average, 70.3 years) and found melanoma to be more common in women (52.5%) than in men. Lesions mainly affected the limbs (32.3%) and head (24.4%), showed signs of ulceration (33.8%), and could be classified into the nodular histological (29%), extensive superficial (27%), and acral (12%) types. The average Breslow index was 1.2 mm. Metastasis occurred in 33% of the patients and mainly affected lymph nodes (36%) and the central nervous system (CNS, 20%). The first procedure conducted in 79% of the cases was surgical resection. Sentinel node mapping was carried out in 41.7% of the cases, and surgical treatment alone was indicated in 70% of the patients. The disease recurred in 34.5% of the patients, and 17.9% succumbed to the disease. These results indicate that the elderly have poorer prognosis when cancer treatment is delayed.
CONCLUSION
Melanoma of the limbs and head, intermediate Breslow index, metastatic lymph node and CNS metastases, and relapse result in fatal outcomes. Direct strategies, such as prevention and early detection, as well as uniform and adequate treatment, are needed to improve disease management in the elderly.
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Melanoma; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Retrospective Studies; Skin Neoplasms
PubMed: 32555965
DOI: 10.1590/0100-6991e-20202441 -
Cells Oct 2021Different types of cells, such as endothelial cells, tumor-associated fibroblasts, pericytes, and immune cells, release extracellular vesicles (EVs) in the tumor... (Review)
Review
Different types of cells, such as endothelial cells, tumor-associated fibroblasts, pericytes, and immune cells, release extracellular vesicles (EVs) in the tumor microenvironment. The components of EVs include proteins, DNA, RNA, and microRNA. One of the most important functions of EVs is the transfer of aforementioned bioactive molecules, which in cancer cells may affect tumor growth, progression, angiogenesis, and metastatic spread. Furthermore, EVs affect the presentation of antigens to immune cells via the transfer of nucleic acids, peptides, and proteins to recipient cells. Recent studies have also explored the potential application of EVs in cancer treatment. This review summarizes the mechanisms by which EVs regulate melanoma development, progression, and their potentials to be applied in therapy. We initially describe vesicle components; discuss their effects on proliferation, anti-melanoma immunity, and drug resistance; and finally focus on the effects of EV-derived microRNAs on melanoma pathobiology. This work aims to facilitate our understanding of the influence of EVs on melanoma biology and initiate ideas for the development of novel therapeutic strategies.
Topics: Animals; Disease Progression; Drug Resistance, Neoplasm; Extracellular Vesicles; Humans; Melanoma; Models, Biological; Skin Neoplasms; Tumor Microenvironment; Melanoma, Cutaneous Malignant
PubMed: 34685720
DOI: 10.3390/cells10102740 -
International Journal of Molecular... Jul 2021Melanoma represents the most malignant type of skin cancer, with increasing incidence worldwide [...].
Melanoma represents the most malignant type of skin cancer, with increasing incidence worldwide [...].
Topics: Humans; Medical Oncology; Melanoma; Neoplasm Metastasis; Precision Medicine; Prognosis; Skin Neoplasms
PubMed: 34299343
DOI: 10.3390/ijms22147723 -
Postepy Biochemii Sep 2023Malignant melanoma is a dangerous skin cancer, accounting for the majority of skin cancer-related deaths. Many patients with this cancer have the V600E mutation in the...
Malignant melanoma is a dangerous skin cancer, accounting for the majority of skin cancer-related deaths. Many patients with this cancer have the V600E mutation in the BRAF gene. This mutation causes constitutive activation of the MAPK/ERK signaling pathway, significantly contributing to the process of carcinogenesis. We discuss the drug design process on the example of a specific BRAF V600E inhibitor, vemurafenib. We begin with the most commonly used drug design methods. The second part of the article focuses on vemurafenib. We analyze the invention of this BRAF V600E inhibitor and its analogue as well as the course of three stages of clinical trials. Then we provide information about other popular drugs for malignant melanoma, i.e. dacarbazine, ipilimumab and dabrafenib, and about the advantages of therapy with the simultaneous use of two inhibitors. Finally, we briefly discuss the role of artificial intelligence in the future of drug design.
Topics: Humans; Vemurafenib; Antineoplastic Agents; Proto-Oncogene Proteins B-raf; Artificial Intelligence; Indoles; Sulfonamides; Melanoma; Skin Neoplasms; Protein Kinase Inhibitors; Mutation; Drug Resistance, Neoplasm; Melanoma, Cutaneous Malignant
PubMed: 38019740
DOI: 10.18388/pb.2021_498 -
International Journal of Molecular... Jul 2021We studied CD34+ stromal cells/telocytes (CD34+SCs/TCs) in pathologic skin, after briefly examining them in normal conditions. We confirm previous studies by other... (Review)
Review
We studied CD34+ stromal cells/telocytes (CD34+SCs/TCs) in pathologic skin, after briefly examining them in normal conditions. We confirm previous studies by other authors in the normal dermis regarding CD34+SC/TC characteristics and distribution around vessels, nerves and cutaneous annexes, highlighting their practical absence in the papillary dermis and presence in the bulge region of perifollicular groups of very small CD34+ stromal cells. In non-tumoral skin pathology, we studied examples of the principal histologic patterns in which CD34+SCs/TCs have (1) a fundamental pathophysiological role, including (a) fibrosing/sclerosing diseases, such as systemic sclerosis, with loss of CD34+SCs/TCs and presence of stromal cells co-expressing CD34 and αSMA, and (b) metabolic degenerative processes, including basophilic degeneration of collagen, with stromal cells/telocytes in close association with degenerative fibrils, and cutaneous myxoid cysts with spindle-shaped, stellate and bulky vacuolated CD34+ stromal cells, and (2) a secondary reactive role, encompassing dermatitis-e.g., interface (erythema multiforme), acantholytic (pemphigus, Hailey-Hailey disease), lichenoid (lichen planus), subepidermal vesicular (bullous pemphigoid), psoriasiform (psoriasis), granulomatous (granuloma annulare)-vasculitis (leukocytoclastic and lymphocytic vasculitis), folliculitis, perifolliculitis and inflammation of the sweat and sebaceous glands (perifolliculitis and rosacea) and infectious dermatitis (verruca vulgaris). In skin tumor and tumor-like conditions, we studied examples of those in which CD34+ stromal cells are (1) the neoplastic component (dermatofibrosarcoma protuberans, sclerotic fibroma and solitary fibrous tumor), (2) a neoplastic component with varying presentation (fibroepithelial polyp and superficial myxofibrosarcoma) and (3) a reactive component in other tumor/tumor-like cell lines, such as those deriving from vessel periendothelial cells (myopericytoma), epithelial cells (trichoepithelioma, nevus sebaceous of Jadassohn and seborrheic keratosis), Merkel cells (Merkel cell carcinoma), melanocytes (dermal melanocytic nevi) and Schwann cells (neurofibroma and granular cell tumor).
Topics: Animals; Antigens, CD34; Dermatitis; Dermis; Humans; Neoplasm Proteins; Skin Neoplasms; Telocytes
PubMed: 34298962
DOI: 10.3390/ijms22147342 -
Oncogene Nov 2021Collagens are the most abundant proteins in the body and comprise the basement membranes and stroma through which cancerous invasion occurs; however, a pro-neoplastic...
Collagens are the most abundant proteins in the body and comprise the basement membranes and stroma through which cancerous invasion occurs; however, a pro-neoplastic function for mutant collagens is undefined. Here we identify COL11A1 mutations in 66 of 100 cutaneous squamous cell carcinomas (cSCCs), the second most common U.S. cancer, concentrated in a triple helical region known to produce trans-dominant collagens. Analysis of COL11A1 and other collagen genes found that they are mutated across common epithelial malignancies. Knockout of mutant COL11A1 impairs cSCC tumorigenesis in vivo. Compared to otherwise genetically identical COL11A1 wild-type tissue, gene-edited mutant COL11A1 skin is characterized by induction of β1 integrin targets and accelerated neoplastic invasion. In mosaic tissue, mutant COL11A1 cells enhanced invasion by neighboring wild-type cells. These results suggest that specific collagens are commonly mutated in cancer and that mutant collagens may accelerate this process.
Topics: Animals; Carcinoma, Squamous Cell; Case-Control Studies; Collagen Type XI; Female; Humans; Integrin beta1; Mice; Mutation; Neoplasm Invasiveness; Neoplasm Transplantation; Protein Structure, Secondary; Skin Neoplasms; Exome Sequencing
PubMed: 34584216
DOI: 10.1038/s41388-021-02013-y