Pigment Cell & Melanoma Research[JOURNAL]
Sun
155 papers
A rare case of fully regressive melanoma in the absence of metastasis.
Kyriakopoulos A, Kyriakopoulos V, Vourlakou C … +3 more , Balasis S, Paronis E, Gogas HJ
Melanoma Res · 2026 Aug · PMID 42228856 · Publisher ↗
Fully regressive melanoma is an exceedingly rare phenomenon characterized by the complete histopathologic disappearance of malignant melanocytes, replaced by fibrosis, melanophages, and lymphocytic infiltrates, without i...
Fully regressive melanoma is an exceedingly rare phenomenon characterized by the complete histopathologic disappearance of malignant melanocytes, replaced by fibrosis, melanophages, and lymphocytic infiltrates, without identifiable residual tumor cells. We report the case of a 71-year-old female who presented with a pigmented lesion of the right auricle, which was incidentally noted by her daughter. Clinical examination revealed a darkly pigmented, asymmetrical macule with retention of hair follicles, raising suspicion for a benign melanocytic nevus. Excisional biopsy revealed complete regression of a superficial spreading melanoma without measurable Breslow thickness or vertical growth phase. Immunohistochemical studies demonstrated positivity for melanocytic markers and a low proliferative index, while imaging with PET/computed tomography and MRI revealed no evidence of regional or distant metastasis. Given the absence of high-risk features, sentinel lymph node biopsy was not performed, and the patient underwent wide local excision with no residual malignancy identified. She remains disease-free under close clinical follow-up. This case highlights the diagnostic and management challenges associated with fully regressive melanoma and emphasizes the need for heightened clinical suspicion and individualized treatment strategies. Further research is required to better understand the prognostic significance and optimal follow-up protocols for this rare melanoma subtype.
Comprehensive clinical imaging, histopathological analysis and liquid biopsy-based surveillance of human uveal melanoma in a prolonged rabbit xenograft model.
Bustamante P, Coblentz J, Mastromonaco C … +18 more , Youhnovska E, Ito H, Proença RP, Fonseca C, Dickinson K, Marcotte E, MacDonald M, Toledo-Dias AB, Bergeron S, Goyeneche A, Schmidt Andujar RA, Tsering T, Laskaris A, Jin E, Nadeau A, Porraccio T, Burnier MN, Burnier JV
Melanoma Res · 2024 Aug · PMID 38847739 · Publisher ↗
Uveal melanoma is the most common intraocular tumor in adults. Our group has previously developed a human uveal melanoma animal model; however, adverse effects caused by the immunosuppressive agent, cyclosporine A, preve...
Uveal melanoma is the most common intraocular tumor in adults. Our group has previously developed a human uveal melanoma animal model; however, adverse effects caused by the immunosuppressive agent, cyclosporine A, prevented animals from surviving more than 12 weeks. In this study, we tested multiple cyclosporine A doses over an extended disease course up to 20 weeks, providing complete clinical imaging of intraocular tumors, histopathological analysis and liquid biopsy biomarker analysis. Twenty albino rabbits were divided into four groups with different daily cyclosporine A schedules (0-10 mg/kg) and inoculated with human uveal melanoma cell lines, 92.1 or MP41, into the suprachoroidal space. Rabbits were monitored with fundoscopy, ultrasound and optical coherence tomography. Intraocular tumors (macroscopic or microscopic) were detected in all study animals. Tumor size and growth were correlated to cyclosporine A dose, with tumors regressing when cyclosporine A was arrested. All tumors expressed HMB-45 and MelanA; however, tumor size, pigmentation and cell morphology differed in 92.1 vs. MP41 tumors. Finally, across all groups, circulating tumor DNA from plasma and aqueous humor was detected earlier than tumor detection by imaging and correlated to tumor growth. In conclusion, using three clinically relevant imaging modalities (fundoscopy, ultrasonography and optical coherence tomography) and liquid biopsy, we were successfully able to monitor tumor progression in our rabbit xenograft model of human uveal melanoma.
A glimpse at locally advanced melanomas in the settings of poverty: pathologist's viewpoint.
Assefa W, Muluye S, Assefa A … +1 more , Alemu Y
Melanoma Res · 2023 Oct · PMID 37310480 · Publisher ↗
Cutaneous melanoma is the most aggressive cancer of the skin arising from pigment-producing cells, known as melanocytes. It is notorious for spreading early to distant locations. Survival of patients with melanoma largel...
Cutaneous melanoma is the most aggressive cancer of the skin arising from pigment-producing cells, known as melanocytes. It is notorious for spreading early to distant locations. Survival of patients with melanoma largely depends on the thickness of the lesion at the primary site thus spotting it early is crucial. Early diagnosis of melanoma, with an improved quality of life and treatment outcomes, is being achieved in some developed nations through screening and health education. On the contrary, as practicing pathologists in a resource-scarce country, we frequently encounter patients with locally advanced melanoma manifesting as ulceration, bleeding, fungation, and bone erosion. Several factors, including low socioeconomic status, medical mistrust, inaccessibility of health facilities, and absent screening and surveillance services can be attributed to the delayed diagnosis. Therefore to alleviate the burden and complications caused by the late presentation of cutaneous melanoma, an urgent massive community mobilization, information campaigning, and the provision of accessible basic primary health care are urgently needed.
Assessment of lipid and pigment content in suspicious melanocytic lesions to improve melanoma detection.
Amara SV, Grbic N, Melson G … +5 more , Brem CE, Almier N, Bhawan J, Alani RM, Collard M
Melanoma Res · 2023 Aug · PMID 37276030 · Publisher ↗
Melanoma is a highly aggressive form of skin cancer and the most frequent lethal malignancy diagnosed by dermatologists. Although there have been advances for predicting melanoma prognosis, there are few highly sensitive...
Melanoma is a highly aggressive form of skin cancer and the most frequent lethal malignancy diagnosed by dermatologists. Although there have been advances for predicting melanoma prognosis, there are few highly sensitive and specific diagnostic tools for clinically evaluating suspicious melanocytic lesions prior to biopsy. We have recently determined that alterations in cellular lipid and pigment content are associated with tumor progression and melanoma metastasis. Here, we seek to determine if lipid droplet and pigment content assessments near the skin's surface are able to distinguish benign from malignant melanocytic lesions. We obtained 14 benign melanocytic lesions, classified as Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) class 1, and 22 malignant melanomas, classified as MPATH-Dx class 4 or 5, from Boston Medical Center. The malignant melanomas had an average greatest thickness of 1.8 ± 2.1 mm with 7/22 biopsies showing the presence of ulceration. Tissues were stained with the Fontana Masson stain to detect pigment or immunohistochemically stained for adipophilin, the main protein component of lipid droplets, to detect lipid droplets. Pigment and lipid droplets were quantified using ImageJ and CellProfiler, respectively. We found no significant difference in total pigment area between benign melanocytic lesions and malignant melanoma, and a 66% decrease in lipid content and 68% reduction in lipid/pigment content between benign melanocytic lesions and malignant melanoma ( P < 0.05). Our results suggest that lipid content and lipid/pigment content ratios may distinguish benign and malignant melanocytic lesions, which may be useful as a diagnostic tool for histopathologically challenging pigmented lesions.
Patients with a history of atopy have fewer cutaneous melanomas than those without atopy: a cross-sectional study in 496 patients at risk of skin cancers.
Komulainen J, Siiskonen H, Haimakainen S … +3 more , Kanasuo E, Harvima RJ, Harvima IT
Melanoma Res · 2023 Jun · PMID 36847301 · Publisher ↗
The connection between atopy and skin cancers may be related to the stimulation of protective immune response, for example, through autoreactive immunoglobulin-E (IgE), or to the predisposition to carcinogenesis through...
The connection between atopy and skin cancers may be related to the stimulation of protective immune response, for example, through autoreactive immunoglobulin-E (IgE), or to the predisposition to carcinogenesis through chronic inflammation. The aim of this study was to investigate whether a past or present atopic disorder is associated with cutaneous photodamage, pigment cell nevi and skin cancers. For this, adult subjects at risk of any type of skin cancer (aged 21-79 years, 250 males, 246 females, 94 with immunosuppression) were examined for past or present malignancies in skin and extracutaneous site (ECS), photodamage, nevi, past or present atopic disorder in skin or mucus membranes, and possible other cancer-related factors. No association between atopy and photodamage, keratinocyte carcinomas or nevus count was found. Instead, there were fewer subjects with melanoma in 171 atopic (14.6%) than in 325 nonatopic subjects (22.2%) ( P = 0.044), and the investigator-estimated risk class of skin cancers was lower in atopic than nonatopic subjects. In all subjects, the multivariate odds ratio (OR) for melanoma was 0.583 ( P = 0.046; 95% confidence interval, 0.343-0.990) in atopic subjects, but in immunocompetent subjects, the reduced risk was confined to mucus membrane atopy (OR, 0.417; P = 0.020). Also, there were fewer subjects with malignancy in ECS in atopic (8.8%) than nonatopic subjects (15.7%) ( P = 0.031). No association between serum total IgE and skin cancers, photodamage, nevi or malignancies in ECS was found. In conclusion, the atopy, especially mucus membrane atopy, is associated with lower percentages of subjects with a history of melanoma.
Regular use of vitamin D supplement is associated with fewer melanoma cases compared to non-use: a cross-sectional study in 498 adult subjects at risk of skin cancers.
Kanasuo E, Siiskonen H, Haimakainen S … +2 more , Komulainen J, Harvima IT
Melanoma Res · 2023 Apr · PMID 36580363 · Publisher ↗
There are conflicting results on the role of vitamin D system in cutaneous carcinogenesis. Therefore, it was investigated whether the use of oral vitamin D supplements associates with photoaging, actinic keratoses, pigme...
There are conflicting results on the role of vitamin D system in cutaneous carcinogenesis. Therefore, it was investigated whether the use of oral vitamin D supplements associates with photoaging, actinic keratoses, pigment cell nevi, and skin cancers. In this cross-sectional study, 498 adults (aged 21-79 years, 253 males, 245 females, 96 with immunosuppression) subjects at risk of any type of skin cancer were examined, and possible confounding factors were evaluated. The subjects were divided into three groups based on their self-reported use of oral vitamin D supplements: non-use, occasional use, or regular use. The serum level of 25-hydroxyvitamin-D3 was analyzed in 260 subjects. In 402 immunocompetent subjects, vitamin D use did not associate with photoaging, actinic keratoses, nevi, basal, and squamous cell carcinoma. In contrast, there were lower percentages of subjects with a history of past or present melanoma (32/177, 18.1% versus 32/99, 32.3%, P = 0.021) or any type of skin cancer (110/177, 62.1% versus 74/99, 74.7%, P = 0.027) among regular users compared to non-users. In the logistic regression analysis, the odds ratio for melanoma was 0.447 ( P = 0.016, 95% confidence interval, 0.231-0.862) among regular users. Furthermore, the investigator-estimated risk class of skin cancers was significantly lower among regular users. Serum 25-hydroxyvitamin-D3 did not show marked associations with skin-related parameters. The results on 96 immunosuppressed subjects were somewhat similar, although the number of subjects was low. In conclusion, regular use of vitamin D associates with fewer melanoma cases, when compared to non-use, but the causality between them is obscure.
Ponatinib-induced eruptive nevi and melanocytic proliferation.
Kim YH, Kim Y, Park TJ … +1 more , Kang HY
Melanoma Res · 2022 Feb · PMID 34939982 · Publisher ↗
Ponatinib, an oral third-generation tyrosine kinase inhibitor, is indicated for the treatment of imatinib-resistant leukemia. We experienced a case of ponatinib-induced eruptive nevi, and the biologic effects of ponatini...
Ponatinib, an oral third-generation tyrosine kinase inhibitor, is indicated for the treatment of imatinib-resistant leukemia. We experienced a case of ponatinib-induced eruptive nevi, and the biologic effects of ponatinib on melanocytes were investigated. Treatment with ponatinib significantly increased the proliferation of normal human melanocyte or melanoma cells through the upregulation of the extracellular signal-regulated kinase and protein kinase B signaling pathways. The downstream molecules of cyclin B1 and D1 were significantly increased in ponatinib-treated melanocytes. These results demonstrate the capacity of ponatinib to induce the proliferation and tumorigenesis of melanocytes.
Histone deacetylase inhibitor Vorinostat (SAHA) suppresses micropthalmia transcription factor expression and induces cell death in nevocytes from large/giant congenital melanocytic nevi.
Basu D, Salgado CM, Bauer B … +4 more , Hoehl RM, Moscinski CN, Schmitt L, Reyes-Múgica M
Melanoma Res · 2021 Aug · PMID 34054057 · Publisher ↗
Large/giant congenital nevi (L/GCMN) are benign neoplasms of the melanocytic neural crest lineage covering extensive areas of skin presenting risk for melanoma. Surgical resection often leads to scarring and trauma. Hist...
Large/giant congenital nevi (L/GCMN) are benign neoplasms of the melanocytic neural crest lineage covering extensive areas of skin presenting risk for melanoma. Surgical resection often leads to scarring and trauma. Histone deacetylase inhibitors (iHDACs) as topical therapeutic agents may prove beneficial as an alternative/adjunct to surgery in this disease. Here we describe the effect of in vitro treatment of iHDACs drugs on primary nevocytes isolated from L/GCMN patients. Micropthalmia transcription factor (MITF) expression in L/GCMN patients' lesions was detected by immunohistochemistry, in cultured nevocytes by immunofluorescence, immunoblot and quantitative polymerase chain reaction. Cellular senescence was detected by SA-ß galactosidase activity. Markers for melanocytic differentiation were evaluated by immunoblot analysis and extracted melanin content was estimated spectrophotometrically. Cell death was measured by lactate dehydrogenase (LDH) assay and necrosis confirmed by polymerase (PARP) cleavage and acridine orange staining of the nuclei. MITF was expressed ubiquitously in nevocytes and melanocytes in patients' lesions. In culture, iHDAC treatment suppressed MITF protein and mRNA expression resulting in a senescent-like phenotype with positive ß-galactosidase staining, progressing to necrotic cell death as evidenced by increased LDH activity, appearance of cleaved PARP and necrotic nuclei. This is the first report showing evidence of iHDACs-induced MITF suppression in congenital nevocytes in vitro leading to a morphologic change with positive ß-galactosidase staining, followed by necrotic cell death in nevocytes, indicating that iHDAC drugs could be valuable therapeutic agents for treatment of L/GCMN lesions.
Novel response to neoadjuvant anti-PD1 therapy for a patient with retrocaval melanotic schwannoma.
Vining CC, Hsu PJ, Miller A … +6 more , Olson DJ, Gajewski TF, Pytel P, Bauer BS, Millis MJ, Roggin KK
Melanoma Res · 2021 Feb · PMID 33323721 · Full text
Melanotic schwannoma is a rare nerve sheath tumor composed of melanin-producing Schwann cells with the potential for metastasis. These tumors can be associated with familial tumor syndromes and can cause significant symp...
Melanotic schwannoma is a rare nerve sheath tumor composed of melanin-producing Schwann cells with the potential for metastasis. These tumors can be associated with familial tumor syndromes and can cause significant symptoms related to nerve compression and mass effect. Due to the rarity of these lesions, they can be initially misidentified as melanocytomas, pigmented dermatofibrosarcoma protuberans, neurofibromas or malignant melanomas. Surgical excision is the mainstay of treatment with limited benefit from adjuvant systemic chemotherapy or radiation. Modern treatments with immune checkpoint blockade have demonstrated significant improvements in progression-free and overall survival for a variety of cancer histologies; however, anti-PD1 therapy has yet to be evaluated in patients with melanotic schwannoma. This report demonstrates a significant improvement in symptomatology and tumor stability with neoadjuvant anti-PD1 therapy for a retrocaval melanotic schwannoma initially masquerading as malignant melanoma. This report demonstrates the potential benefit of a novel therapeutic option for patients with melanotic schwannoma.
Distinguishing melanophages from tumor in melanoma patients treated with talimogene laherparepvec.
Audrey-Bayan C, Trager MH, Gartrell-Corrado RD … +8 more , Rizk EM, Pradhan J, Silverman AM, Lopez A, Marks DK, Niedt G, Geskin LJ, Saenger YM
Melanoma Res · 2020 Aug · PMID 32379409 · Full text
Response to talimogene laherparepvec (T-Vec) is difficult to assess as pigmented macrophages that have ingested melanoma cells ('melanophages') persist after injection, mimicking melanoma. We used quantitative immunofluo...
Response to talimogene laherparepvec (T-Vec) is difficult to assess as pigmented macrophages that have ingested melanoma cells ('melanophages') persist after injection, mimicking melanoma. We used quantitative immunofluorescence (qIF) to (1) distinguish melanophages from melanoma in biopsies from two patients treated with T-Vec and (2) evaluate the tumor microenvironment pretreatment and posttreatment. Tissues were stained with 4',6-diamidino-2-phenylindole, cluster of differentiation (CD) 3, CD8, CD68, human leukocyte antigen-DR isotype (HLA-DR), and SRY-Box Transcription Factor 10 (SOX10), and multispectral images were analyzed. Post-T-Vec samples showed melanophages with cytoplasmic costaining of CD68, SOX10, and HLA-DR, without nuclear SOX10 expression. qIF revealed a dense immune infiltrate of CD3, CD8, and CD68 cells in post-T-Vec samples. Melanophages from tumors post-T-Vec stain the nuclear melanoma marker SOX10 in their cytoplasms as compared to melanoma cells that stain nuclear SOX10. This novel finding highlights the phagocytosis of melanoma cell components by macrophages after treatment with T-Vec. qIF may assist pathologists in determining whether lesions treated with immunotherapy contain residual viable melanoma.
Genome-wide study on uveal melanoma patients finds association to DNA repair gene TDP1.
Thomsen H, Chattopadhyay S, Hoffmann P … +6 more , Nöthen MM, Kalirai H, Coupland SE, Jonas JB, Hemminki K, Försti A
Melanoma Res · 2020 Apr · PMID 31626034 · Publisher ↗
Uveal melanoma is a life-threatening disease for which data on germline predisposition are essentially limited to mutations in the BAP1 gene. Many risk factors are shared between uveal melanoma and cutaneous melanoma, an...
Uveal melanoma is a life-threatening disease for which data on germline predisposition are essentially limited to mutations in the BAP1 gene. Many risk factors are shared between uveal melanoma and cutaneous melanoma, and these include fair skin color and light eye color. We carried out a genome-wide association study on 590 uveal melanoma patients and 5199 controls. Using a P-value limit of 10 we identified 11 loci with related odds ratios for the risk alleles ranging from 1.32 to 1.78. The smallest P-value in the overall analysis reached 1.07 × 10 for rs3759710 at 14q32.11, which is intronic to TDP1 (tyrosyl-DNA phosphodiesterase 1). This locus emerged as a genome-wide significant association for uveal melanoma clinical subtypes with any chromosomal aberrations (P = 10) and presence of epithelioid cells (P = 10). TDP1 is a DNA repair enzyme capable of repairing many types of DNA damage, including oxidative DNA lesions which may be relevant for uveal melanoma. We additionally wanted to replicate the previous candidate locus for uveal melanoma at chromosome 5p15.33 intronic to the CLPTM1L gene. Our analysis gave an odds ratio of 1.23 (95% confidence interval: 1.09-1.38; P = 0.0008) for the C allele of rs421284 and 1.21 (95% confidence interval: 1.07-1.36; P = 0.002) for the C allele of rs452932. Our data thus replicated the association of uveal melanoma with the CLPTM1L locus. Our data on TDP1 offer an attractive model positing that oxidative damage in pigmented tissue may be an initiation event in uveal melanoma and the level of damage may be regulated by the degree and type of iris pigmentation.
Biomarkers, measured during therapy, for response of melanoma patients to immune checkpoint inhibitors: a systematic review.
Ouwerkerk W, van den Berg M, van der Niet S … +2 more , Limpens J, Luiten RM
Melanoma Res · 2019 Oct · PMID 30855527 · Full text
Immune checkpoint inhibitors (ICIs), which target CTLA-4 or PD-(L)1 molecules, have shown impressive therapeutic results. Durable responses, however, are only observed in a segment of the patient population and must be o...
Immune checkpoint inhibitors (ICIs), which target CTLA-4 or PD-(L)1 molecules, have shown impressive therapeutic results. Durable responses, however, are only observed in a segment of the patient population and must be offset against severe off-target immune toxicity and high costs. This calls for biomarkers that predict response during ICI treatment. Although many candidate biomarkers exist, as yet, there has been no systematic overview of biomarkers predictive during. Here, we provide a systematic review of the current literature of ICI treatment to establish an overview of candidate predictive biomarkers during ICI treatment in melanoma patients. We performed a systematic Medline search (2000-2018, 1 January) on biomarkers for survival or response to ICI treatment in melanoma patients. We retrieved 735 publications, of which 79 were finally included in this systematic review. Blood markers were largely studied for CTLA-4 ICI, whereas tumor tissue markers were analyzed for PD-(L)1 ICI. Blood cytology and soluble factors were more frequently correlated to overall survival (OS) than response, indicating their prognostic rather than predictive nature. An increase in tumor-infiltrating CD8 + T-cells and a decrease in regulatory T-cells were correlated to response, in addition to mutational load, neoantigen load, and immune-related gene expression. Immune-related adverse events were also associated frequently with a favorable response and OS. This review shows the great variety of potential biomarkers published to date, in an attempt to better understand response to ICI therapy; it also highlights the candidate markers for future research. The most promising biomarkers for response to ICI treatment are the occurrence of immune-related adverse events (especially vitiligo), lowering of lactate dehydrogenase, and increase in activated CD8 + and decrease in regulatory T-cells.
Nuclear morphometric analysis in tissue as an objective tool with potential use to improve melanoma staging.
Nunes TWN, Filippi-Chiela EC, Callegari-Jacques SM … +4 more , da Silva VD, Sansonowicz T, Lenz G, Roehe AV
Melanoma Res · 2019 Oct · PMID 30839356 · Publisher ↗
Alterations in nuclear size and shape are commonly observed in cancers, and its objective evaluation may provide valuable clinical information about the outcome of the disease. Here, we applied the nuclear morphometric a...
Alterations in nuclear size and shape are commonly observed in cancers, and its objective evaluation may provide valuable clinical information about the outcome of the disease. Here, we applied the nuclear morphometric analysis in tissues in hematoxylin and eosin-digitized slides of nevi and melanoma, to objectively contribute to the prognostic evaluation of these tumors. To this, we analyzed the nuclear morphometry of 34 melanomas classified according to the TNM stage. Eight cases of melanocytic nevi were used as non-neoplastic tissues to set the non-neoplastic parameters of nuclear morphology. Our samples were set as G1 (control, nevi), G2 (T1T2N0M0), G3 (T3T4N0M0), G4 (T1T2N1M1), and G5 (T3T4N1M1). Image-Pro Plus 6.0 software was used to acquire measurements related to nuclear size (variable: Area) and shape (variables: Aspect, AreaBox, Roundness, and RadiusRatio, which were used to generate the Nuclear Irregularity Index). From these primary variables, a set of secondary variables were generated. All the seven primary and secondary variables related to the nuclear area were different among groups (Pillai's trace P<0.001), whereas Nuclear Irregularity Index, which is the variable related to nuclear shape, did not differ among groups. The secondary variable 'Average Area of Large Nuclei' was able to differ all pairwise comparisons, including thin nonmetastatic from thin metastatic tumors. In conclusion, the objective quantification of nuclear area in hematoxylin and eosin slides may provide objective information about the risk stratification of these tumors and has the potential to be used as an additional method in clinical decision making.
Expression of cancer/testis antigens in cutaneous melanoma: a systematic review.
Tio D, Kasiem FR, Willemsen M … +5 more , van Doorn R, van der Werf N, Hoekzema R, Luiten RM, Bekkenk MW
Melanoma Res · 2019 Aug · PMID 30615012 · Publisher ↗
The cancer/testis antigen (CTA) family is a group of antigens whose expression is restricted to male germline cells of the testis and various malignancies. This expression pattern makes this group of antigens potential t...
The cancer/testis antigen (CTA) family is a group of antigens whose expression is restricted to male germline cells of the testis and various malignancies. This expression pattern makes this group of antigens potential targets for immunotherapy. The aim of this study was to create an overview of CTA expressed by melanoma cells at mRNA and protein level. A systematic literature search was performed in Medline (PubMed) and Embase from inception up to and including February 2018. Studies were screened for eligibility by two independent reviewers. A total of 65 full-text articles were included in the final analysis. A total of 48 CTA have been studied in melanoma. Various CTA show different expression rates in primary and metastatic tumours. Of the 48 CTA, the most studied were MAGE-A3, MAGE-A1, NY-ESO-1, MAGE-A4, SSX2, MAGE-A2, MAGE-C1/CT7, SSX1, MAGE-C2/CT10 and MAGE-A12. On average, MAGE-A3 mRNA is present in 36% of primary tumours, whereas metastatic tumours have an expression rate of 55-81%. The same applies to the protein expression rate of MAGE-A3 in primary tumours, which is reported to be at 15-37%, whereas metastatic tumours have a higher expression rate of 25-70%. This trend of increased expression in metastases compared with primary tumours is observed with MAGE-A1, MAGE-A2, MAGE-A4, MAGE-A12 and NY-ESO-1. Many CTA are expressed on melanoma. This review provides an overview of the expression frequency of CTAs in melanoma and may aid in identifying CTA as the therapeutic target for immunotherapy.
MiR-135b is a novel oncogenic factor in cutaneous melanoma by targeting LATS2.
Hu Y, Wang Q, Zhu XH
Melanoma Res · 2019 Apr · PMID 30480622 · Publisher ↗
Melanoma develops from pigment-producing melanocytes in the epidermis, and is the most common type of skin cancer. Because of the lack of effective therapies, the median survival of patients developing metastatic melanom...
Melanoma develops from pigment-producing melanocytes in the epidermis, and is the most common type of skin cancer. Because of the lack of effective therapies, the median survival of patients developing metastatic melanoma is less the 1 year. In this paper, we studied the oncogenic role of miR-135b in melanoma cells. We compared the miR-135b levels in 20 melanoma tissues in reference to their corresponding nontumor regions. Next, we studied the impact of miR-135b or its inhibitor on cell proliferation, migration, or apoptosis in either primary melanocytes or the melanoma cell line, respectively. Finally, we validated large tumor suppressor kinase 2 (LATS2) as the downstream target of miR-135b in a luciferase reporter assay, western blotting analysis, and knockdown study in primary melanocytes. MiR-135b expression was significantly upregulated in melanoma tissue. Overexpressing miR-135b in primary melanocytes promoted cell proliferation and migration. In contrast, inhibition of miR-135b expression suppressed the growth and metastasis of A-375 cells and enhanced cell apoptosis. LATS2 was confirmed as the target of miR-135b. Knockdown of LATS2 in melanocytes also promoted cell growth, but not cell invasion potential. Our findings showed miR-135b as a novel oncogene in melanoma tumorigenesis. The oncogenic mechanism may involve the downregulation of LATS2.
Attenuation of genome-wide 5-methylcytosine level is an epigenetic feature of cutaneous malignant melanomas.
Micevic G, Theodosakis N, Taube JM … +2 more , Bosenberg MW, Rodić N
Melanoma Res · 2017 Apr · PMID 27997431 · Full text
Epigenetic modification of DNA, namely covalent changes of cytosine residues, plays a key role in the maintenance of inactive chromatin regions, both in health and in disease. In the vast majority of malignant melanomas,...
Epigenetic modification of DNA, namely covalent changes of cytosine residues, plays a key role in the maintenance of inactive chromatin regions, both in health and in disease. In the vast majority of malignant melanomas, the most notable known epigenetic abnormality is the attenuation of 5-hydroxymethylcytosine (5-hmC) residues. However, it remains unknown whether a decrease in 5-hmC represents a primary defect of melanoma cancer epigenome or whether it is secondary to the loss of 5-methylcytosine (5-mC), a chemical substrate for 5-hmC. Here, we evaluated 5-mC levels in a spectrum of melanocytic proliferations. To study the epigenetic features of melanocytic nuclei, we began by measuring 5-mC levels in histologic specimens semiquantitatively by immunohistochemistry. We next treated established melanoma cell lines with S-adenosyl methionine (SAM), a universal methyl group donor, in an effort to cause changes in 5-mC levels. We detected a marked reduction in 5-mC levels in both primary and metastatic melanomas compared with 5-mC levels in benign melanocytic nevi. We also empirically induced changes in 5-mC in melanoma cell lines by incubation with SAM. To our surprise, we observed a significant cytoreductive effect of SAM on all melanoma cell lines examined. At subcytotoxic levels, SAM treatment is accompanied by a genome-wide increase in 5-mC. Moreover, we recorded a dose-dependent increase in genome-wide 5-mC levels in melanoma cell lines following SAM treatment. Taken together, we report that genome-wide attenuation of 5-mC is a hallmark of malignant melanomas. We propose that genome-wide attenuation of 5-mC is not merely an epiphenomenon as it is required for melanoma cell growth, albeit by an as of yet undetermined mechanism. Given its potential benefit in slowing down the growth of melanoma cells, SAM should be studied further to determine its role in epigenome modulation.
Primary malignant melanoma of the urinary bladder: clinical, morphological, and molecular analysis of five cases.
Karabulut YY, Erdogan S, Sayar H … +2 more , Ergen A, Ertoy Baydar D
Melanoma Res · 2016 Dec · PMID 27603550 · Publisher ↗
The aim of our study was to evaluate the clinical and morphological features of primary malignant melanomas of the urinary bladder. We obtained information on five such cases from three different institutions. These were...
The aim of our study was to evaluate the clinical and morphological features of primary malignant melanomas of the urinary bladder. We obtained information on five such cases from three different institutions. These were three men and two women between 52 and 76 years of age. Three tumors presented with hematuria, one with dysuria, and one was discovered incidentally on imaging studies. All were invasive to muscularis propria on transuretral resections performed for diagnosis. Neoplastic cells showed variable patterns (large cell epithelioid, small cell diffuse, storiform, or mixed) in different tumors. Pigmentation was prominent in all except one case. Each case was labeled diffusely for S-100, HMB-45, and Melan-A. Pan-cytokeratin showed a perinuclear dot-like reaction in two tumors. Three cases showed the BRAF mutation in molecular studies. Two patients were already metastatic at the time of diagnosis. Two patients died, one is alive with disease after 15 months, and two patients are disease free at 1 and 5 years of surveillance.
Melanocytoma-like melanoma may be the missing link between benign and malignant uveal melanocytic lesions in humans and dogs: a comparative study.
Zoroquiain P, Mayo-Goldberg E, Alghamdi S … +5 more , Alhumaid S, Perlmann E, Barros P, Mayo N, Burnier MN
Melanoma Res · 2016 Dec · PMID 27571324 · Publisher ↗
The cutoff presented in the current classification of canine melanocytic lesions by Wilcock and Pfeiffer is based on the clinical outcome rather than morphological concepts. Classification of tumors based on morphology o...
The cutoff presented in the current classification of canine melanocytic lesions by Wilcock and Pfeiffer is based on the clinical outcome rather than morphological concepts. Classification of tumors based on morphology or molecular signatures is the key to identifying new therapies or prognostic factors. Therefore, the aim of this study was to analyze morphological findings in canine melanocytic lesions based on classic malignant morphologic principles of neoplasia and to compare these features with human uveal melanoma (HUM) samples. In total, 64 canine and 111 human morphologically malignant melanocytic lesions were classified into two groups (melanocytoma-like or classic melanoma) based on the presence or absence of M cells, respectively. Histopathological characteristics were compared between the two groups using the χ-test, t-test, and multivariate discriminant analysis. Among the 64 canine tumors, 28 (43.7%) were classic and 36 (56.3%) were melanocytoma-like melanomas. Smaller tumor size, a higher degree of pigmentation, and lower mitotic activity distinguished melanocytoma-like from classic tumors with an accuracy of 100% for melanocytoma-like lesions. From the human series, only one case showed melanocytoma-like features and had a low risk for metastasis characteristics. Canine uveal melanoma showed a morphological spectrum with features similar to the HUM counterpart (classic melanoma) and overlapped features between uveal melanoma and melanocytoma (melanocytoma-like melanoma). Recognition that the subgroup of melanocytoma-like melanoma may represent the missing link between benign and malignant lesions could help explain the progression of uveal melanoma in dogs; these findings can potentially be translated to HUM.
Melanoma masquerading as nonmelanocytic lesions.
Detrixhe A, Libon F, Mansuy M … +6 more , Nikkels-Tassoudji N, Rorive A, Arrese JE, Quatresooz P, Reginster MA, Nikkels AF
Melanoma Res · 2016 Dec · PMID 27537773 · Publisher ↗
Increased awareness among dermatologists as well as the development of dermoscopy and sequential dermoscopy have contributed significantly toward an increase in the diagnostic accuracy of pigmented melanoma and even of a...
Increased awareness among dermatologists as well as the development of dermoscopy and sequential dermoscopy have contributed significantly toward an increase in the diagnostic accuracy of pigmented melanoma and even of amelanotic melanoma. However, the dermatologist's nightmare is the small group of melanomas that present as common skin diseases, often associated with a significant delay in diagnosis and hence a poor prognosis. The study was carried out to prospectively assess the number of melanomas lacking any clinical suspicion of melanoma and to describe their clinical and histological features over a 6-year observation period in an University Tertiary Skin Cancer Center. Out of 502 cases of newly diagnosed cases of melanoma, seven (1.4%) nonpigmented and nonamelanotic cases of melanoma were identified. The mean age of the patients was 69 years (two females/five males). All cases were discovered by chance on a punch biopsy. The clinical diagnostic suspicions were basal cell carcinoma, fungal intertrigo, keratoacanthoma, lichenoid keratoma, diabetic foot ulcer, eczema, and necrotic pressure ulcer. Dermoscopy, performed after the punch biopsies, was only partially contributive. The mean histological thickness was 2.7 mm, the mean number of mitoses was 7/mm, local micrometastases were present in 5/7 (71%), the mean Ki67 count was 18.9%, and a positive sentinel lymph node was observed in 4/6 (66%) cases. Nonpigmented and nonamelanotic melanomas are rare, are at high risk, and have a poor prognosis because of a delayed diagnosis. Dermoscopy is only of partial diagnostic aid. Treatment resistance or atypical behavior of the above-mentioned lesions should lead to biopsy.
Endothelin-1 in the tumor microenvironment correlates with melanoma invasion.
Chiriboga L, Meehan S, Osman I … +6 more , Glick M, de la Cruz G, Howell BS, Friedman-Jiménez G, Schneider RJ, Jamal S
Melanoma Res · 2016 Jun · PMID 26825037 · Publisher ↗
Endothelin-1 (ET-1) is a vasoactive peptide that also plays a role in the tanning response of the skin. Animal and cell culture studies have also implicated ET-1 in melanoma progression, but no association studies have b...
Endothelin-1 (ET-1) is a vasoactive peptide that also plays a role in the tanning response of the skin. Animal and cell culture studies have also implicated ET-1 in melanoma progression, but no association studies have been performed to link ET-1 expression and melanoma in humans. Here, we present the first in-vivo study of ET-1 expression in pigmented lesions in humans: an ET-1 immunohistochemical screen of melanocytic nevi, melanoma in situ lesions, invasive melanomas, metastatic melanomas, and blue nevi was performed. Twenty-six percent of melanocytic nevi and 44% of melanoma in situ lesions demonstrate ET-1 expression in the perilesional microenvironment, whereas expression in nevus or melanoma cells was rare to absent. In striking contrast, 100% of moderately to highly pigmented invasive melanomas contained numerous ET-1-positive cells in the tumor microenvironment, with 79% containing ET-1-positive melanoma cells, confirmed by co-staining with melanoma tumor marker HMB45. Hypopigmented invasive melanomas had reduced ET-1 expression, suggesting a correlation between ET-1 expression and pigmented melanomas. ET-1-positive perilesional cells were CD68-positive, indicating macrophage origin. Sixty-two percent of highly pigmented metastatic melanomas demonstrated ET-1 expression in melanoma cells, in contrast to 28.2% of hypopigmented specimens. Eighty-nine percent of benign nevi, known as blue nevi, which have a dermal localization, were associated with numerous ET-1-positive macrophages in the perilesional microenvironment, but no ET-1 expression was detected in the melanocytes. We conclude that ET-1 expression in the microenvironment increases with advancing stages of melanocyte transformation, implicating a critical role for ET-1 in melanoma progression, and the importance of the tumor microenvironment in the melanoma phenotype.
About
- Frequency
- Sun
- Papers found
- 155
- RSS feed
- Subscribe