Cutaneous Melanoma: A Review of Multifactorial Pathogenesis, Immunohistochemistry, and Emerging Biomarkers for Early Detection and Management
Abstract
1. Introduction
2. Melanoma Pathogenesis
3. Diagnostic and Prognostic Immunohistochemical Markers in CM
4. Emerging Biomarkers in CM
4.1. MicroRNA
4.2. Exosomes
4.3. Melanoma-Inhibiting Activity
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Leonardi, G.C.; Falzone, L.; Salemi, R.; Zanghì, A.; Spandidos, D.A.; Mccubrey, J.A.; Candido, S.; Libra, M. Cutaneous melanoma: From pathogenesis to therapy (Review). Int. J. Oncol. 2018, 52, 1071–1080. [Google Scholar] [CrossRef] [PubMed]
- Davis, L.E.; Shalin, S.C.; Tackett, A.J. Current state of melanoma diagnosis and treatment. Cancer Biol. Ther. 2019, 20, 1366–1379. [Google Scholar] [CrossRef] [PubMed]
- Orzan, O.A.; Șandru, A.; Jecan, C.R. Controversies in the diagnosis and treatment of early cutaneous melanoma. J. Med. Life 2015, 8, 132–141. [Google Scholar] [PubMed]
- Caini, S.; Gandini, S.; Sera, F.; Raimondi, S.; Fargnoli, M.C.; Boniol, M.; Armstrong, B.K. Meta-analysis of risk factors for cutaneous melanoma according to anatomical site and clinico-pathological variant. Eur. J. Cancer. 2009, 45, 3054–3063. [Google Scholar] [CrossRef] [PubMed]
- Burns, D.; George, J.; Aucoin, D.; Bower, J.; Burrell, S.; Gilbert, R.; Bower, N. The Pathogenesis and Clinical Management of Cutaneous Melanoma: An Evidence-Based Review. J. Med. Imaging Radiat. Sci. 2019, 50, 460–469.e1. [Google Scholar] [CrossRef] [PubMed]
- Rigel, D.S.; Carucci, J.A. Malignant melanoma: Prevention, early detection, and treatment in the 21st century. CA Cancer J. Clin. 2000, 50, 215–236. [Google Scholar] [CrossRef] [PubMed]
- Țăpoi, D.A.; Derewicz, D.; Gheorghișan-Gălățeanu, A.-A.; Dumitru, A.V.; Ciongariu, A.M.; Costache, M. The Impact of Clinical and Histopathological Factors on Disease Progression and Survival in Thick Cutaneous Melanomas. Biomedicines 2023, 11, 2616. [Google Scholar] [CrossRef] [PubMed]
- Cust, A.E.; Mishra, K.; Berwick, M. Melanoma—Role of the environment and genetics. Photochem. Photobiol. Sci. 2018, 17, 1853–1860. [Google Scholar] [CrossRef]
- Gandini, S.; Sera, F.; Cattaruzza, M.S.; Pasquini, P.; Picconi, O.; Boyle, P.; Melchi, C.F. Meta-analysis of risk factors for cutaneous melanoma: II. Sun exposure. Eur. J. Cancer. 2005, 41, 45–60. [Google Scholar] [CrossRef]
- de Gruijl, F.R. UV adaptation: Pigmentation and protection against overexposure. Exp. Dermatol. 2017, 26, 557–562. [Google Scholar] [CrossRef]
- Elder, D.E.; Barnhill, R.Y. (Eds.) Chapter III: Melanocytic neoplasms. In WHO Classification of Tumours Editorial Board. Skin Tumours, 5th ed.; Forthcoming; International Agency for Research on Cancer: Lyon, France, 2023; Volume 12, Available online: https://tumourclassification.iarc.who.int/chapters/64 (accessed on 27 August 2023).
- Ribeiro Moura Brasil Arnaut, J.; Dos Santos Guimarães, I.; Evangelista Dos Santos, A.C.; de Moraes Lino da Silva, F.; Machado, J.R.; de Melo, A.C. Molecular landscape of Hereditary Melanoma. Crit. Rev. Oncol. Hematol. 2021, 164, 103425. [Google Scholar] [CrossRef] [PubMed]
- Tímár, J.; Ladányi, A. Molecular Pathology of Skin Melanoma: Epidemiology, Differential Diagnostics, Prognosis and Therapy Prediction. Int. J. Mol. Sci. 2022, 23, 5384. [Google Scholar] [CrossRef] [PubMed]
- Cakir, A.; Elcin, G.; Kilickap, S.; Gököz, Ö.; Taskiran, Z.E.; Celik, İ. Phenotypic and Genetic Features that Differ Between Hereditary and Sporadic Melanoma: Results of a Preliminary Study from a Single Center from Turkey. Dermatol. Pract. Concept. 2023, 13, e2023146. [Google Scholar] [CrossRef] [PubMed]
- Vogelstein, B.; Papadopoulos, N.; Velculescu, V.E.; Zhou, S.; Diaz, L.A., Jr.; Kinzler, K.W. Cancer genome landscapes. Science 2013, 339, 1546–1558. [Google Scholar] [CrossRef] [PubMed]
- Cancer Genome Atlas Network. Genomic Classification of Cutaneous Melanoma. Cell 2015, 161, 1681–1696. [Google Scholar] [CrossRef] [PubMed]
- Țăpoi, D.A.; Gheorghișan-Gălățeanu, A.-A.; Dumitru, A.V.; Ciongariu, A.M.; Furtunescu, A.R.; Marin, A.; Costache, M. Primary Undifferentiated/Dedifferentiated Cutaneous Melanomas—A Review on Histological, Immunohistochemical, and Molecular Features with Emphasis on Prognosis and Treatment. Int. J. Mol. Sci. 2023, 24, 9985. [Google Scholar] [CrossRef]
- Chappell, W.H.; Steelman, L.S.; Long, J.M.; Kempf, R.C.; Abrams, S.L.; Franklin, R.A.; Bäsecke, J.; Stivala, F.; Donia, M.; Fagone, P.; et al. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: Rationale and importance to inhibiting these pathways in human health. Oncotarget 2011, 2, 135–164. [Google Scholar] [CrossRef]
- Hodis, E.; Watson, I.R.; Kryukov, G.V.; Arold, S.T.; Imielinski, M.; Theurillat, J.P.; Nickerson, E.; Auclair, D.; Li, L.; Place, C.; et al. A landscape of driver mutations in melanoma. Cell 2012, 150, 251–263. [Google Scholar] [CrossRef]
- Krauthammer, M.; Kong, Y.; Ha, B.H.; Evans, P.; Bacchiocchi, A.; McCusker, J.P.; Cheng, E.; Davis, M.J.; Goh, G.; Choi, M.; et al. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma. Nat. Genet. 2012, 44, 1006–1014. [Google Scholar] [CrossRef]
- Wellbrock, C.; Karasarides, M.; Marais, R. The RAF proteins take centre stage. Nat. Rev. Mol. Cell. Biol. 2004, 5, 875–885. [Google Scholar] [CrossRef]
- Raman, M.; Chen, W.; Cobb, M.H. Differential regulation and properties of MAPKs. Oncogene 2007, 26, 3100–3112. [Google Scholar] [CrossRef] [PubMed]
- Cohen, C.; Zavala-Pompa, A.; Sequeira, J.H.; Shoji, M.; Sexton, D.G.; Cotsonis, G.; Cerimele, F.; Govindarajan, B.; Macaron, N.; Arbiser, J.L. Mitogen-actived protein kinase activation is an early event in melanoma progression. Clin. Cancer Res. 2002, 8, 3728–3733. [Google Scholar] [PubMed]
- Wang, Y.F.; Jiang, C.C.; Kiejda, K.A.; Gillespie, S.; Zhang, X.D.; Hersey, P. Apoptosis induction in human melanoma cells by inhibition of MEK is caspase-independent and mediated by the Bcl-2 family members PUMA, Bim, and Mcl-1. Clin. Cancer Res. 2007, 13, 4934–4942. [Google Scholar] [CrossRef] [PubMed]
- Carlino, M.S.; Long, G.V.; Kefford, R.F.; Rizos, H. Targeting oncogenic BRAF and aberrant MAPK activation in the treatment of cutaneous melanoma. Crit. Rev. Oncol. Hematol. 2015, 96, 385–398. [Google Scholar] [CrossRef] [PubMed]
- Yuan, T.L.; Cantley, L.C. PI3K pathway alterations in cancer: Variations on a theme. Oncogene 2008, 27, 5497–5510. [Google Scholar] [CrossRef] [PubMed]
- Davies, M.A. The role of the PI3K-AKT pathway in melanoma. Cancer J. 2012, 18, 142–147. [Google Scholar] [CrossRef] [PubMed]
- Gray-Schopfer, V.; Wellbrock, C.; Marais, R. Melanoma biology and new targeted therapy. Nature 2007, 445, 851–857. [Google Scholar] [CrossRef] [PubMed]
- Lin, J.Y.; Fisher, D.E. Melanocyte biology and skin pigmentation. Nature 2007, 445, 843–850. [Google Scholar] [CrossRef]
- Davis, E.J.; Johnson, D.B.; Sosman, J.A.; Chandra, S. Melanoma: What do all the mutations mean? Cancer 2018, 124, 3490–3499. [Google Scholar] [CrossRef]
- Davies, H.; Bignell, G.R.; Cox, C.; Stephens, P.; Edkins, S.; Clegg, S.; Teague, J.; Woffendin, H.; Garnett, M.J.; Bottomley, W.; et al. Mutations of the BRAF gene in human cancer. Nature 2002, 417, 949–954. [Google Scholar] [CrossRef]
- Wan, P.T.; Garnett, M.J.; Roe, S.M.; Lee, S.; Niculescu-Duvaz, D.; Good, V.M.; Jones, C.M.; Marshall, C.J.; Springer, C.J.; Barford, D.; et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 2004, 116, 855–867. [Google Scholar] [CrossRef] [PubMed]
- Richtig, G.; Hoeller, C.; Kashofer, K.; Aigelsreiter, A.; Heinemann, A.; Kwong, L.N.; Pichler, M.; Richtig, E. Beyond the BRAFV600E hotspot: Biology and clinical implications of rare BRAF gene mutations in melanoma patients. Br. J. Dermatol. 2017, 177, 936–944. [Google Scholar] [CrossRef] [PubMed]
- Curtin, J.A.; Fridlyand, J.; Kageshita, T.; Patel, H.N.; Busam, K.J.; Kutzner, H.; Cho, K.H.; Aiba, S.; Bröcker, E.B.; LeBoit, P.E.; et al. Distinct sets of genetic alterations in melanoma. N. Engl. J. Med. 2005, 353, 2135–2147. [Google Scholar] [CrossRef] [PubMed]
- Jakob, J.A.; Bassett, R.L., Jr.; Ng, C.S.; Curry, J.L.; Joseph, R.W.; Alvarado, G.C.; Rohlfs, M.L.; Richard, J.; Gershenwald, J.E.; Kim, K.B.; et al. NRAS mutation status is an independent prognostic factor in metastatic melanoma. Cancer 2012, 118, 4014–4023. [Google Scholar] [CrossRef] [PubMed]
- Giehl, K. Oncogenic Ras in tumour progression and metastasis. Biol. Chem. 2005, 386, 193–205. [Google Scholar] [CrossRef] [PubMed]
- Fedorenko, I.V.; Gibney, G.T.; Smalley, K.S. NRAS mutant melanoma: Biological behavior and future strategies for therapeutic management. Oncogene 2013, 32, 3009–3018. [Google Scholar] [CrossRef] [PubMed]
- Maertens, O.; Johnson, B.; Hollstein, P.; Frederick, D.T.; Cooper, Z.A.; Messiaen, L.; Bronson, R.T.; McMahon, M.; Granter, S.; Flaherty, K.; et al. Elucidating distinct roles for NF1 in melanomagenesis. Cancer Discov. 2013, 3, 338–349. [Google Scholar] [CrossRef] [PubMed]
- Whittaker, S.R.; Theurillat, J.P.; Van Allen, E.; Wagle, N.; Hsiao, J.; Cowley, G.S.; Schadendorf, D.; Root, D.E.; Garraway, L.A. A genome-scale RNA interference screen implicates NF1 loss in resistance to RAF inhibition. Cancer Discov. 2013, 3, 350–362. [Google Scholar] [CrossRef]
- Gibney, G.T.; Smalley, K.S. An unholy alliance: Cooperation between BRAF and NF1 in melanoma development and BRAF inhibitor resistance. Cancer Discov. 2013, 3, 260–263. [Google Scholar] [CrossRef]
- Nissan, M.H.; Pratilas, C.A.; Jones, A.M.; Ramirez, R.; Won, H.; Liu, C.; Tiwari, S.; Kong, L.; Hanrahan, A.J.; Yao, Z.; et al. Loss of NF1 in cutaneous melanoma is associated with RAS activation and MEK dependence. Cancer Res. 2014, 74, 2340–2350. [Google Scholar] [CrossRef]
- Thielmann, C.M.; Chorti, E.; Matull, J.; Murali, R.; Zaremba, A.; Lodde, G.; Jansen, P.; Richter, L.; Kretz, J.; Möller, I.; et al. NF1-mutated melanomas reveal distinct clinical characteristics depending on tumour origin and respond favourably to immune checkpoint inhibitors. Eur. J. Cancer 2021, 159, 113–124. [Google Scholar] [CrossRef] [PubMed]
- Beadling, C.; Jacobson-Dunlop, E.; Hodi, F.S.; Le, C.; Warrick, A.; Patterson, J.; Town, A.; Harlow, A.; Cruz, F., 3rd; Azar, S.; et al. KIT gene mutations and copy number in melanoma subtypes. Clin. Cancer Res. 2008, 14, 6821–6828. [Google Scholar] [CrossRef] [PubMed]
- Handolias, D.; Salemi, R.; Murray, W.; Tan, A.; Liu, W.; Viros, A.; Dobrovic, A.; Kelly, J.; McArthur, G.A. Mutations in KIT occur at low frequency in melanomas arising from anatomical sites associated with chronic and intermittent sun exposure. Pigment. Cell Melanoma Res. 2010, 23, 210–215. [Google Scholar] [CrossRef] [PubMed]
- Pham, D.D.M.; Guhan, S.; Tsao, H. KIT and Melanoma: Biological Insights and Clinical Implications. Yonsei Med. J. 2020, 61, 562–571. [Google Scholar] [CrossRef] [PubMed]
- Loras, A.; Gil-Barrachina, M.; Marqués-Torrejón, M.Á.; Perez-Pastor, G.; Martinez-Cadenas, C. UV-Induced Somatic Mutations Driving Clonal Evolution in Healthy Skin, Nevus, and Cutaneous Melanoma. Life 2022, 12, 1339. [Google Scholar] [CrossRef] [PubMed]
- Wagstaff, W.; Mwamba, R.N.; Grullon, K.; Armstrong, M.; Zhao, P.; Hendren-Santiago, B.; Qin, K.H.; Li, A.J.; Hu, D.A.; Youssef, A.; et al. Melanoma: Molecular genetics, metastasis, targeted therapies, immunotherapies, and therapeutic resistance. Genes Dis. 2022, 9, 1608–1623. [Google Scholar] [CrossRef] [PubMed]
- Tadijan, A.; Precazzini, F.; Hanžić, N.; Radić, M.; Gavioli, N.; Vlašić, I.; Ozretić, P.; Pinto, L.; Škreblin, L.; Barban, G.; et al. Altered Expression of Shorter p53 Family Isoforms Can Impact Melanoma Aggressiveness. Cancers 2021, 13, 5231. [Google Scholar] [CrossRef]
- Loureiro, J.B.; Raimundo, L.; Calheiros, J.; Carvalho, C.; Barcherini, V.; Lima, N.R.; Gomes, C.; Almeida, M.I.; Alves, M.G.; Costa, J.L.; et al. Targeting p53 for Melanoma Treatment: Counteracting Tumour Proliferation, Dissemination and Therapeutic Resistance. Cancers 2021, 13, 1648. [Google Scholar] [CrossRef]
- Wu, H.; Goel, V.; Haluska, F.G. PTEN signaling pathways in melanoma. Oncogene 2003, 22, 3113–3122. [Google Scholar] [CrossRef]
- Tsao, H.; Goel, V.; Wu, H.; Yang, G.; Haluska, F.G. Genetic interaction between NRAS and BRAF mutations and PTEN/MMAC1 inactivation in melanoma. J. Investig. Dermatol. 2004, 122, 337–341. [Google Scholar] [CrossRef]
- Stahl, J.M.; Cheung, M.; Sharma, A.; Trivedi, N.R.; Shanmugam, S.; Robertson, G.P. Loss of PTEN promotes tumor development in malignant melanoma. Cancer Res. 2003, 63, 2881–2890. [Google Scholar] [PubMed]
- Nogueira, C.; Kim, K.H.; Sung, H.; Paraiso, K.H.; Dannenberg, J.H.; Bosenberg, M.; Chin, L.; Kim, M. Cooperative interactions of PTEN deficiency and RAS activation in melanoma metastasis. Oncogene 2010, 29, 6222–6232. [Google Scholar] [CrossRef] [PubMed]
- Shi, H.; Hugo, W.; Kong, X.; Hong, A.; Koya, R.C.; Moriceau, G.; Chodon, T.; Guo, R.; Johnson, D.B.; Dahlman, K.B.; et al. Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy. Cancer Discov. 2014, 4, 80–93. [Google Scholar] [CrossRef] [PubMed]
- McCubrey, J.A.; Steelman, L.S.; Kempf, C.R.; Chappell, W.H.; Abrams, S.L.; Stivala, F.; Malaponte, G.; Nicoletti, F.; Libra, M.; Bäsecke, J.; et al. Therapeutic resistance resulting from mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR signaling pathways. J. Cell. Physiol. 2011, 226, 2762–2781. [Google Scholar] [CrossRef] [PubMed]
- Steelman, L.S.; Chappell, W.H.; Abrams, S.L.; Kempf, R.C.; Long, J.; Laidler, P.; Mijatovic, S.; Maksimovic-Ivanic, D.; Stivala, F.; Mazzarino, M.C.; et al. Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging. Aging 2011, 3, 192–1222. [Google Scholar] [CrossRef] [PubMed]
- McCubrey, J.A.; Steelman, L.S.; Chappell, W.H.; Abrams, S.L.; Franklin, R.A.; Montalto, G.; Cervello, M.; Libra, M.; Candido, S.; Malaponte, G.; et al. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascade inhibitors: How mutations can result in therapy resistance and how to overcome resistance. Oncotarget 2012, 3, 1068–1111. [Google Scholar] [CrossRef] [PubMed]
- Messina, J.L.; Glass, L.F.; Cruse, C.W.; Berman, C.; Ku, N.K.; Reintgen, D.S. Pathologic examination of the sentinel lymph node in malignant melanoma. Am. J. Surg. Pathol. 1999, 23, 686–690. [Google Scholar] [CrossRef] [PubMed]
- Lam, G.T.; Martini, C.; Brooks, T.; Prabhakaran, S.; Hopkins, A.M.; Ung, B.S.-Y.; Tang, J.; Caruso, M.C.; Brooks, R.D.; Johnson, I.R.D.; et al. Insights into Melanoma Clinical Practice: A Perspective for Future Research. Cancers 2023, 15, 4631. [Google Scholar] [CrossRef]
- Saleem, A.; Narala, S.; Raghavan, S.S. Immunohistochemistry in melanocytic lesions: Updates with a practical review for pathologists. Semin. Diagn. Pathol. 2022, 39, 239–247. [Google Scholar] [CrossRef]
- Marques, P.C.; Diniz, L.M.; Spelta, K.; Nogueira, P.S.E. Desmoplastic melanoma: A rare variant with challenging diagnosis. An. Bras. Dermatol. 2019, 94, 82–85. [Google Scholar] [CrossRef]
- Cochran, A.J.; Wen, D.R.; Morton, D.L. Occult tumor cells in the lymph nodes of patients with pathological stage I malignant melanoma. An immunohistological study. Am. J. Surg. Pathol. 1988, 12, 612–618. [Google Scholar] [CrossRef] [PubMed]
- Tirado-Sánchez, A. Recalcitrant primary cutaneous Rosai-Dorfman disease. Efficacy of sirolimus and intralesional methylprednisolone. Skin. Health Dis. 2023, 3, e273. [Google Scholar] [CrossRef] [PubMed]
- Aisner, D.L.; Maker, A.; Rosenberg, S.A.; Berman, D.M. Loss of S100 antigenicity in metastatic melanoma. Hum. Pathol. 2005, 36, 1016–1019. [Google Scholar] [CrossRef] [PubMed]
- Xia, J.; Wang, Y.; Li, F.; Wang, J.; Mu, Y.; Mei, X.; Li, X.; Zhu, W.; Jin, X.; Yu, K. Expression of microphthalmia transcription factor, S100 protein, and HMB-45 in malignant melanoma and pigmented nevi. Biomed. Rep. 2016, 5, 327–331. [Google Scholar] [CrossRef] [PubMed]
- Pop, A.M.; Monea, M.; Olah, P.; Moraru, R.; Cotoi, O.S. The Importance of Immunohistochemistry in the Evaluation of Tumor Depth of Primary Cutaneous Melanoma. Diagnostics 2023, 13, 1020. [Google Scholar] [CrossRef] [PubMed]
- Dass, S.E.; Huizenga, T.; Farshchian, M.; Mehregan, D.R. Comparison of SOX-10, HMB-45, and Melan-A in Benign Melanocytic Lesions. Clin. Cosmet. Investig. Dermatol. 2021, 14, 1419–1425. [Google Scholar] [CrossRef] [PubMed]
- Hussein, M.R.A. HMB45 protein expression and the immunohistochemical maturation in common blue nevi: A reappraisal. An. Bras. Dermatol. 2022, 97, 387–390. [Google Scholar] [CrossRef]
- Zand, S.; Buzney, E.; Duncan, L.M.; Dadras, S.S. Heterogeneity of Metastatic Melanoma: Correlation of MITF With Its Transcriptional Targets MLSN1, PEDF, HMB-45, and MART-1. Am. J. Clin. Pathol. 2016, 146, 353–360. [Google Scholar] [CrossRef][Green Version]
- Zubovits, J.; Buzney, E.; Yu, L.; Duncan, L.M. HMB-45, S-100, NK1/C3, and MART-1 in metastatic melanoma. Hum. Pathol. 2004, 35, 217–223. [Google Scholar] [CrossRef]
- Drabeni, M.; Lopez-Vilaró, L.; Barranco, C.; Trevisan, G.; Gallardo, F.; Pujol, R.M. Differences in tumor thickness between hematoxylin and eosin and Melan-A immunohistochemically stained primary cutaneous melanomas. Am. J. Dermatopathol. 2013, 35, 56–63. [Google Scholar] [CrossRef]
- Megahed, M.; Schön, M.; Selimovic, D.; Schön, M.P. Reliability of diagnosis of melanoma in situ. Lancet 2002, 359, 1921–1922. [Google Scholar] [CrossRef] [PubMed]
- Panse, G.; McNiff, J.M. Lichenoid dermatoses with pseudomelanocytic nests vs inflamed melanoma in situ: A comparative study. J. Cutan. Pathol. 2021, 48, 745–749. [Google Scholar] [CrossRef] [PubMed]
- Muzumdar, S.; Argraves, M.; Kristjansson, A.; Ferenczi, K.; Dadras, S.S. A quantitative comparison between SOX10 and MART-1 immunostaining to detect melanocytic hyperplasia in chronically sun-damaged skin. J. Cutan. Pathol. 2018, 45, 263–268. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.; Taube, J.M.; McCalmont, T.H.; Glusac, E.J. Quantitative comparison of MiTF, Melan-A, HMB-45 and Mel-5 in solar lentigines and melanoma in situ. J. Cutan. Pathol. 2011, 38, 775–779. [Google Scholar] [CrossRef] [PubMed]
- Agaimy, A.; Stoehr, R.; Hornung, A.; Popp, J.; Erdmann, M.; Heinzerling, L.; Hartmann, A. Dedifferentiated and Undifferentiated Melanomas: Report of 35 New Cases With Literature Review and Proposal of Diagnostic Criteria. Am. J. Surg. Pathol. 2021, 45, 240–254. [Google Scholar] [CrossRef] [PubMed]
- Luzar, B.; Billings, S.D.; de la Fouchardiere, A.; Pissaloux, D.; Alberti, L.; Calonje, E. Compound Clear Cell Sarcoma of the Skin-A Potential Diagnostic Pitfall: Report of a Series of 4 New Cases and a Review of the Literature. Am. J. Surg. Pathol. 2020, 44, 21–29. [Google Scholar] [CrossRef] [PubMed]
- Westover, C.; Bacchi, C.; Gru, A.A. Clear Cell Sarcoma with Cutaneous Presentation in a 4-Year-Old Boy. Am. J. Dermatopathol. 2020, 42, e131–e133. [Google Scholar] [CrossRef]
- Cazzato, G.; Colagrande, A.; Lospalluti, L.; Pacello, L.; Lettini, T.; Arezzo, F.; Loizzi, V.; Lupo, C.; Casatta, N.; Cormio, G.; et al. Primitive Cutaneous (P)erivascular (E)pithelioid (C)ell Tumour (PEComa): A New Case Report of a Rare Cutaneous Tumor. Genes 2022, 13, 1153. [Google Scholar] [CrossRef]
- Gaspard, M.; Lamant, L.; Tournier, E.; Valentin, T.; Rochaix, P.; Terrier, P.; Ranchere-Vince, D.; Coindre, J.M.; Filleron, T.; Le Guellec, S. Evaluation of eight melanocytic and neural crest-associated markers in a well-characterised series of 124 malignant peripheral nerve sheath tumours (MPNST): Useful to distinguish MPNST from melanoma? Histopathology 2018, 73, 969–982. [Google Scholar] [CrossRef]
- Mackie, R.M.; Campbell, I.; Turbitt, M.L. Use of NK1 C3 monoclonal antibody in the assessment of benign and malignant melanocytic lesions. J. Clin. Pathol. 1984, 37, 367–372. [Google Scholar] [CrossRef]
- Sulaimon, S.; Kitchell, B.; Ehrhart, E. Immunohistochemical detection of melanoma-specific antigens in spontaneous canine melanoma. J. Comp. Pathol. 2002, 127, 162–168. [Google Scholar] [CrossRef] [PubMed]
- Orchard, G.; Wilson Jones, E. Immunocytochemistry in the diagnosis of malignant melanoma. Br. J. Biomed. Sci. 1994, 51, 44–56. [Google Scholar] [PubMed]
- Ramachandra, S.; Gillett, C.E.; Millis, R.R. A comparative immunohistochemical study of mammary and extramammary Paget’s disease and superficial spreading melanoma, with particular emphasis on melanocytic markers. Virchows Arch. 1996, 429, 371–376. [Google Scholar] [CrossRef] [PubMed]
- Yu, L.L.; Flotte, T.J.; Tanabe, K.K.; Gadd, M.A.; Cosimi, A.B.; Sober, A.J.; Mihm, M.C., Jr.; Duncan, L.M. Detection of microscopic melanoma metastases in sentinel lymph nodes. Cancer 1999, 86, 617–627. [Google Scholar] [CrossRef]
- Lezcano, C.; Jungbluth, A.A.; Nehal, K.S.; Hollmann, T.J.; Busam, K.J. PRAME Expression in Melanocytic Tumors. Am. J. Surg. Pathol. 2018, 42, 1456–1465. [Google Scholar] [CrossRef] [PubMed]
- Lezcano, C.; Pulitzer, M.; Moy, A.P.; Hollmann, T.J.; Jungbluth, A.A.; Busam, K.J. Immunohistochemistry for PRAME in the Distinction of Nodal Nevi From Metastatic Melanoma. Am. J. Surg. Pathol. 2020, 44, 503–508. [Google Scholar] [CrossRef]
- Lezcano, C.; Jungbluth, A.A.; Busam, K.J. PRAME Immunohistochemistry as an Ancillary Test for the Assessment of Melanocytic Lesions. Surg. Pathol. Clin. 2021, 14, 165–175. [Google Scholar] [CrossRef] [PubMed]
- Roy, S.F.; Panse, G.; McNiff, J.M. PRAME immunohistochemistry can distinguish melanocytic pseudonests of lichenoid reactions from melanoma in situ. J. Cutan. Pathol. 2023, 50, 450–454. [Google Scholar] [CrossRef]
- Hrycaj, S.M.; Szczepanski, J.M.; Zhao, L.; Siddiqui, J.; Thomas, D.G.; Lucas, D.R.; Patel, R.M.; Harms, P.W.; Bresler, S.C.; Chan, M.P. PRAME expression in spindle cell melanoma, malignant peripheral nerve sheath tumour, and other cutaneous sarcomatoid neoplasms: A comparative analysis. Histopathology 2022, 81, 818–825. [Google Scholar] [CrossRef]
- Kline, N.; Menge, T.D.; Hrycaj, S.M.; Andea, A.A.; Patel, R.M.; Harms, P.W.; Chan, M.P.; Bresler, S.C. PRAME Expression in Challenging Dermal Melanocytic Neoplasms and Soft Tissue Tumors with Melanocytic Differentiation. Am. J. Dermatopathol. 2022, 44, 404–410. [Google Scholar] [CrossRef]
- Clarke, L.E.; Flake, D.D., 2nd; Busam, K.; Cockerell, C.; Helm, K.; McNiff, J.; Reed, J.; Tschen, J.; Kim, J.; Barnhill, R.; et al. An independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi. Cancer 2017, 123, 617–628. [Google Scholar] [CrossRef]
- Ko, J.S.; Matharoo-Ball, B.; Billings, S.D.; Thomson, B.J.; Tang, J.Y.; Sarin, K.Y.; Cai, E.; Kim, J.; Rock, C.; Kimbrell, H.Z.; et al. Diagnostic Distinction of Malignant Melanoma and Benign Nevi by a Gene Expression Signature and Correlation to Clinical Outcomes. Cancer Epidemiol. Biomark. Prev. 2017, 26, 1107–1113. [Google Scholar] [CrossRef] [PubMed]
- Ferris, L.K.; Jansen, B.; Ho, J.; Busam, K.J.; Gross, K.; Hansen, D.D.; Alsobrook, J.P., 2nd; Yao, Z.; Peck, G.L.; Gerami, P. Utility of a Noninvasive 2-Gene Molecular Assay for Cutaneous Melanoma and Effect on the Decision to Biopsy. JAMA Dermatol. 2017, 153, 675–680. [Google Scholar] [CrossRef] [PubMed]
- Hemminger, J.A.; Toland, A.E.; Scharschmidt, T.J.; Mayerson, J.L.; Guttridge, D.C.; Iwenofu, O.H. Expression of cancer-testis antigens MAGEA1, MAGEA3, ACRBP, PRAME, SSX2, and CTAG2 in myxoid and round cell liposarcoma. Mod. Pathol. 2014, 27, 1238–1245. [Google Scholar] [CrossRef] [PubMed]
- Iura, K.; Kohashi, K.; Hotokebuchi, Y.; Ishii, T.; Maekawa, A.; Yamada, Y.; Yamamoto, H.; Iwamoto, Y.; Oda, Y. Cancer-testis antigens PRAME and NY-ESO-1 correlate with tumour grade and poor prognosis in myxoid liposarcoma. J. Pathol. Clin. Res. 2015, 1, 144–159. [Google Scholar] [CrossRef] [PubMed]
- Iura, K.; Maekawa, A.; Kohashi, K.; Ishii, T.; Bekki, H.; Otsuka, H.; Yamada, Y.; Yamamoto, H.; Harimaya, K.; Iwamoto, Y.; et al. Cancer-testis antigen expression in synovial sarcoma: NY-ESO-1, PRAME, MAGEA4, and MAGEA1. Hum. Pathol. 2017, 61, 130–139. [Google Scholar] [CrossRef]
- Cammareri, C.; Beltzung, F.; Michal, M.; Vanhersecke, L.; Coindre, J.M.; Velasco, V.; Le Loarer, F.; Vergier, B.; Perret, R. PRAME immunohistochemistry in soft tissue tumors and mimics: A study of 350 cases highlighting its imperfect specificity but potentially useful diagnostic applications. Virchows Arch. 2023, 483, 145–156. [Google Scholar] [CrossRef] [PubMed]
- Xu, Y.; Zou, R.; Wang, J.; Wang, Z.W.; Zhu, X. The role of the cancer testis antigen PRAME in tumorigenesis and immunotherapy in human cancer. Cell Prolif. 2020, 53, e12770. [Google Scholar] [CrossRef]
- Yakout, N.M.; Abdallah, D.M.; Abdelmonsif, D.A.; Kholosy, H.M.; Talaat, I.M.; Elsakka, O. BRAFV600E mutational status assessment in cutaneous melanocytic neoplasms in a group of the Egyptian population. Cancer Cell. Int. 2023, 23, 17. [Google Scholar] [CrossRef]
- Maksimaityte, V.; Reivytyte, R.; Milaknyte, G.; Mickys, U.; Razanskiene, G.; Stundys, D.; Kazenaite, E.; Valantinas, J.; Stundiene, I. Metastatic multifocal melanoma of multiple organ systems: A case report. World J. Clin. Cases 2022, 10, 10136–10145. [Google Scholar] [CrossRef]
- Rothrock, A.T.; Hameed, N.; Cho, W.C.; Nagarajan, P.; Ivan, D.; Torres-Cabala, C.A.; Prieto, V.G.; Curry, J.L.; Aung, P.P. BRAF V600E immunohistochemistry as a useful tool in the diagnosis of melanomas with ambiguous morphologies and immunophenotypes. J. Cutan. Pathol. 2023, 50, 223–229. [Google Scholar] [CrossRef] [PubMed]
- Orchard, G.E.; Wojcik, K.; Rickaby, W.; Martin, B.; Semkova, K.; Shams, F.; Stefanato, C.M. Immunohistochemical detection of V600E BRAF mutation is a useful primary screening tool for malignant melanoma. Br. J. Biomed. Sci. 2019, 76, 77–82. [Google Scholar] [CrossRef] [PubMed]
- Saliba, E.; Bhawan, J. Aberrant Expression of Immunohistochemical Markers in Malignant Melanoma: A Review. Dermatopathology 2021, 8, 359–370. [Google Scholar] [CrossRef]
- Ferreira, I.; Arends, M.J.; van der Weyden, L.; Adams, D.J.; Brenn, T. Primary de-differentiated, trans-differentiated and undifferentiated melanomas: Overview of the clinicopathological, immunohistochemical and molecular spectrum. Histopathology 2022, 80, 135–149. [Google Scholar] [CrossRef] [PubMed]
- Han, L.M.; Lee, K.W.; Uludag, G.; Seider, M.I.; Afshar, A.R.; Bloomer, M.M.; Pekmezci, M. Prognostic Value of BAP1 and Preferentially Expressed Antigen in Melanoma (PRAME) Immunohistochemistry in Uveal Melanomas. Mod. Pathol. 2023, 36, 100081. [Google Scholar] [CrossRef]
- Parra, O.; Ma, W.; Li, Z.; Coffing, B.N.; Linos, K.; LeBlanc, R.E.; Momtahen, S.; Sriharan, A.; Cloutier, J.M.; Wells, W.A.; et al. PRAME expression in cutaneous melanoma does not correlate with disease-specific survival. J. Cutan. Pathol. 2023, 50, 903–912. [Google Scholar] [CrossRef] [PubMed]
- Gassenmaier, M.; Hahn, M.; Metzler, G.; Bauer, J.; Yazdi, A.S.; Keim, U.; Garbe, C.; Wagner, N.B.; Forchhammer, S. Diffuse PRAME Expression Is Highly Specific for Thin Melanomas in the Distinction from Severely Dysplastic Nevi but Does Not Distinguish Metastasizing from Non-Metastasizing Thin Melanomas. Cancers 2021, 13, 3864. [Google Scholar] [CrossRef]
- Du, Y.; Li, C.; Mao, L.; Wei, X.; Bai, X.; Chi, Z.; Cui, C.; Sheng, X.; Lian, B.; Tang, B.; et al. A nomogram incorporating Ki67 to predict survival of acral melanoma. J. Cancer Res. Clin. Oncol. 2023, 20, 13077–13085. [Google Scholar] [CrossRef]
- Liu, Q.; Peng, Z.; Shen, L.; Shen, L. Prognostic and Clinicopathological Value of Ki-67 in Melanoma: A Meta-Analysis. Front. Oncol. 2021, 11, 737760. [Google Scholar] [CrossRef]
- Ghafouri-Fard, S.; Gholipour, M.; Taheri, M. MicroRNA Signature in Melanoma: Biomarkers and Therapeutic Targets. Front. Oncol. 2021, 11, 608987. [Google Scholar] [CrossRef]
- Poniewierska-Baran, A.; Słuczanowska-Głąbowska, S.; Małkowska, P.; Sierawska, O.; Zadroga, Ł.; Pawlik, A.; Niedźwiedzka-Rystwej, P. Role of miRNA in Melanoma Development and Progression. Int. J. Mol. Sci. 2023, 24, 201. [Google Scholar] [CrossRef] [PubMed]
- Bennett, P.E.; Bemis, L.; Norris, D.A.; Shellman, Y.G. miR in melanoma development: miRNAs and acquired hallmarks of cancer in melanoma. Physiol. Genom. 2013, 45, 1049–1059. [Google Scholar] [CrossRef] [PubMed]
- Díaz-Martínez, M.; Benito-Jardón, L.; Alonso, L.; Koetz-Ploch, L.; Hernando, E.; Teixidó, J. miR-204-5p and miR-211-5p Contribute to BRAF Inhibitor Resistance in Melanoma. Cancer Res. 2018, 78, 1017–1030. [Google Scholar] [CrossRef] [PubMed]
- Motti, M.L.; Minopoli, M.; Di Carluccio, G.; Ascierto, P.A.; Carriero, M.V. MicroRNAs as Key Players in Melanoma Cell Resistance to MAPK and Immune Checkpoint Inhibitors. Int. J. Mol. Sci. 2020, 21, 4544. [Google Scholar] [CrossRef] [PubMed]
- Zhang, J.; Zhao, H.; Gao, Y.; Zhang, W. Secretory miRNAs as novel cancer biomarkers. Biochim. Biophys. Acta 2012, 1826, 32–43. [Google Scholar] [CrossRef] [PubMed]
- Li, J.; Liu, Y.; Wang, C.; Deng, T.; Liang, H.; Wang, Y.; Huang, D.; Fan, Q.; Wang, X.; Ning, T.; et al. Serum miRNA expression profile as a prognostic biomarker of stage II/III colorectal adenocarcinoma. Sci. Rep. 2015, 5, 12921. [Google Scholar] [CrossRef] [PubMed]
- Hanniford, D.; Zhong, J.; Koetz, L.; Gaziel-Sovran, A.; Lackaye, D.J.; Shang, S.; Pavlick, A.; Shapiro, R.; Berman, R.; Darvishian, F.; et al. A miRNA-Based Signature Detected in Primary Melanoma Tissue Predicts Development of Brain Metastasis. Clin. Cancer Res. 2015, 21, 4903–4912. [Google Scholar] [CrossRef]
- Stark, M.S.; Klein, K.; Weide, B.; Haydu, L.E.; Pflugfelder, A.; Tang, Y.H.; Palmer, J.M.; Whiteman, D.C.; Scolyer, R.A.; Mann, G.J.; et al. The Prognostic and Predictive Value of Melanoma-related MicroRNAs Using Tissue and Serum: A MicroRNA Expression Analysis. EBioMedicine 2015, 2, 671–680. [Google Scholar] [CrossRef]
- Antonova, E.; Hambikova, A.; Shcherbakov, D.; Sukhov, V.; Vysochanskaya, S.; Fadeeva, I.; Gorshenin, D.; Sidorova, E.; Kashutina, M.; Zhdanova, A.; et al. Determination of Common microRNA Biomarker Candidates in Stage IV Melanoma Patients and a Human Melanoma Cell Line: A Potential Anti-Melanoma Agent Screening Model. Int. J. Mol. Sci. 2023, 24, 9160. [Google Scholar] [CrossRef]
- Vitiello, M.; D’Aurizio, R.; Poliseno, L. Biological role of miR-204 and miR-211 in melanoma. Oncoscience 2018, 5, 248–251. [Google Scholar] [CrossRef][Green Version]
- Varrone, F.; Caputo, E. The miRNAs Role in Melanoma and in Its Resistance to Therapy. Int. J. Mol. Sci. 2020, 21, 878. [Google Scholar] [CrossRef] [PubMed]
- Qian, L.-Y.; Li, P.; He, Q.-Y.; Luo, C.-Q. Circulating miR-221 Expression Level and Prognosis of Cutaneous Malignant Melanoma. Experiment 2014, 20, 2472–2477. [Google Scholar] [CrossRef] [PubMed]
- Rigg, E.; Wang, J.; Xue, Z.; Lunavat, T.R.; Liu, G.; Hoang, T.; Parajuli, H.; Han, M.; Bjerkvig, R.; Nazarov, P.V.; et al. Inhibition of extracellular vesicle-derived miR-146a-5p decreases progression of melanoma brain metastasis via Notch pathway dysregulation in astrocytes. J. Extracell. Vesicles 2023, 12, e12363. [Google Scholar] [CrossRef] [PubMed]
- Bell, R.E.; Khaled, M.; Netanely, D.; Schubert, S.; Golan, T.; Buxbaum, A.; Janas, M.M.; Postolsky, B.; Goldberg, M.S.; Shamir, R.; et al. Transcription factor/microRNA axis blocks melanoma invasion program by miR-211 targeting NUAK1. J. Investig. Dermatol. 2014, 134, 441–451. [Google Scholar] [CrossRef] [PubMed]
- Luan, W.; Li, R.; Liu, L.; Ni, X.; Shi, Y.; Xia, Y.; Wang, J.; Lu, F.; Xu, B. Long non-coding RNA HOTAIR acts as a competing endogenous RNA to promote malignant melanoma progression by sponging miR-152-3p. Oncotarget 2017, 8, 85401–85414. [Google Scholar] [CrossRef] [PubMed]
- Rang, Z.; Yang, G.; Wang, Y.W.; Cui, F. miR-542-3p suppresses invasion and metastasis by targeting the proto-oncogene serine/threonine protein kinase, PIM1, in melanoma. Biochem. Biophys. Res. Commun. 2016, 474, 315–320. [Google Scholar] [CrossRef] [PubMed]
- Nabipoorashrafi, S.A.; Shomali, N.; Sadat-Hatamnezhad, L.; Mahami-Oskouei, M.; Mahmoudi, J.; Shotorbani, B.S.; Akbari, M.; Xu, H. miR-143 acts as an inhibitor of migration and proliferation as well as an inducer of apoptosis in melanoma cancer cells in vitro. IUBMB Life 2020, 72, 2034–2044. [Google Scholar] [CrossRef]
- Liu, Y.; Ruan, H.; Lu, F.; Peng, H.; Luan, W. miR-224-5p acts as a tumour suppressor and reverses the resistance to BRAF Inhibitor In melanoma through directly targeting PAK4 to block the MAPK pathway. Pathol. Res. Pract. 2023, 249, 154772. [Google Scholar] [CrossRef]
- Sun, X.; Li, J.; Sun, Y.; Zhang, Y.; Dong, L.; Shen, C.; Yang, L.; Yang, M.; Li, Y.; Shen, G.; et al. miR-7 reverses the resistance to BRAFi in melanoma by targeting EGFR/IGF-1R/CRAF and inhibiting the MAPK and PI3K/AKT signaling pathways. Oncotarget 2016, 7, 53558–53570. [Google Scholar] [CrossRef]
- Caporali, S.; Amaro, A.; Levati, L.; Alvino, E.; Lacal, P.M.; Mastroeni, S.; Ruffini, F.; Bonmassar, L.; Antonini Cappellini, G.C.; Felli, N.; et al. miR-126-3p down-regulation contributes to dabrafenib acquired resistance in melanoma by up-regulating ADAM9 and VEGF-A. J. Exp. Clin. Cancer Res. 2019, 38, 272. [Google Scholar] [CrossRef]
- Diaz-Martinez, M.; Benito-Jardon, L.; Teixido, J. New insights in melanoma resistance to BRAF inhibitors: A role for microRNAs. Oncotarget 2018, 9, 35374–35375. [Google Scholar] [CrossRef] [PubMed]
- Zheng, Y.; Sun, Y.; Liu, Y.; Zhang, X.; Li, F.; Li, L.; Wang, J. The miR-31-SOX10 axis regulates tumor growth and chemotherapy resistance of melanoma via PI3K/AKT pathway. Biochem. Biophys. Res. Commun. 2018, 503, 2451–2458. [Google Scholar] [CrossRef] [PubMed]
- Surman, M.; Jankowska, U.; Wilczak, M.; Przybyło, M. Similarities and Differences in the Protein Composition of Cutaneous Melanoma Cells and Their Exosomes Identified by Mass Spectrometry. Cancers 2023, 15, 1097. [Google Scholar] [CrossRef] [PubMed]
- Whiteside, T.L. Immunosuppressive functions of melanoma cell-derived exosomes in plasma of melanoma patients. Front. Cell Dev. Biol. 2023, 10, 1080925. [Google Scholar] [CrossRef] [PubMed]
- Zhu, H.; Zhang, P.; Shi, J.; Kou, D.; Bai, X. Exosome-delivered circRPS5 inhibits the progression of melanoma via regulating the miR-151a/NPTX1 axis. PLoS ONE 2023, 18, e0287347. [Google Scholar] [CrossRef] [PubMed]
- Shen, Y.; Li, M.; Liao, L.; Gao, S.; Wang, Y. Plasma exosome-derived connexin43 as a promising biomarker for melanoma patients. BMC Cancer 2023, 23, 242. [Google Scholar] [CrossRef] [PubMed]
- Boussadia, Z.; Lamberti, J.; Mattei, F.; Pizzi, E.; Puglisi, R.; Zanetti, C.; Pasquini, L.; Fratini, F.; Fantozzi, L.; Felicetti, F.; et al. Acidic microenvironment plays a key role in human melanoma progression through a sustained exosome mediated transfer of clinically relevant metastatic molecules. J. Exp. Clin. Cancer Res. 2018, 37, 245. [Google Scholar] [CrossRef]
- Surman, M.; Kędracka-Krok, S.; Hoja-Łukowicz, D.; Jankowska, U.; Drożdż, A.; Stępień, E.Ł.; Przybyło, M. Mass Spectrometry-Based Proteomic Characterization of Cutaneous Melanoma Ectosomes Reveals the Presence of Cancer-Related Molecules. Int. J. Mol. Sci. 2020, 21, 2934. [Google Scholar] [CrossRef]
- Lattmann, E.; Levesque, M.P. The Role of Extracellular Vesicles in Melanoma Progression. Cancers 2022, 14, 3086. [Google Scholar] [CrossRef]
- Strnadová, K.; Pfeiferová, L.; Přikryl, P.; Dvořánková, B.; Vlčák, E.; Frýdlová, J.; Vokurka, M.; Novotný, J.; Šáchová, J.; Hradilová, M.; et al. Exosomes produced by melanoma cells significantly influence the biological properties of normal and cancer-associated fibroblasts. Histochem. Cell Biol. 2022, 157, 153–172. [Google Scholar] [CrossRef]
- Xiao, D.; Barry, S.; Kmetz, D.; Egger, M.; Pan, J.; Rai, S.N.; Qu, J.; McMasters, K.M.; Hao, H. Melanoma cell-derived exosomes promote epithelial-mesenchymal transition in primary melanocytes through paracrine/autocrine signaling in the tumor microenvironment. Cancer Lett. 2016, 376, 318–327. [Google Scholar] [CrossRef] [PubMed]
- Biagioni, A.; Laurenzana, A.; Menicacci, B.; Peppicelli, S.; Andreucci, E.; Bianchini, F.; Guasti, D.; Paoli, P.; Serratì, S.; Mocali, A.; et al. uPAR-expressing melanoma exosomes promote angiogenesis by VE-Cadherin, EGFR and uPAR overexpression and rise of ERK1,2 signaling in endothelial cells. Cell Mol. Life Sci. 2021, 78, 3057–3072. [Google Scholar] [CrossRef] [PubMed]
- García-Silva, S.; Benito-Martín, A.; Nogués, L.; Hernández-Barranco, A.; Mazariegos, M.S.; Santos, V.; Hergueta-Redondo, M.; Ximénez-Embún, P.; Kataru, R.P.; Lopez, A.A.; et al. Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis through an NGFR-dependent mechanism. Nat. Cancer 2021, 2, 1387–1405. [Google Scholar] [CrossRef] [PubMed]
- Wang, P.; Wu, Y.; Chen, W.; Zhang, M.; Qin, J. Malignant melanoma-derived exosomes induce endothelial damage and glial activation on a human BBB chip model. Biosensors 2022, 12, 89. [Google Scholar] [CrossRef] [PubMed]
- Ye, Q.; Li, Z.; Li, Y.; Li, Y.; Zhang, Y.; Gui, R.; Cui, Y.; Zhang, Q.; Qian, L.; Xiong, Y.; et al. Exosome-Derived microRNA: Implications in Melanoma Progression, Diagnosis and Treatment. Cancers 2023, 15, 80. [Google Scholar] [CrossRef] [PubMed]
- Tan, Y.; Tang, F.; Li, J.; Yu, H.; Wu, M.; Wu, Y.; Zeng, H.; Hou, K.; Zhang, Q. Tumor-derived exosomes: The emerging orchestrators in melanoma. Biomed. Pharmacother. 2022, 149, 112832. [Google Scholar] [CrossRef] [PubMed]
- Gerloff, D.; Lützkendorf, J.; Moritz, R.K.C.; Wersig, T.; Mäder, K.; Müller, L.P.; Sunderkötter, C. Melanoma-Derived Exosomal miR-125b-5p Educates Tumor Associated Macrophages (TAMs) by Targeting Lysosomal Acid Lipase A (LIPA). Cancers 2020, 12, 464. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; Liu, Y.; Yang, L.; Jiang, Y.; Qian, Q. TIM-3 shuttled by MV3 cells-secreted exosomes inhibits CD4+ T cell immune function and induces macrophage M2 polarization to promote the growth and metastasis of melanoma cells. Transl. Oncol. 2022, 18, 101334. [Google Scholar] [CrossRef]
- Zhou, Q.; Fang, T.; Wei, S.; Chai, S.; Yang, H.; Tao, M.; Cao, Y. Macrophages in melanoma: A double-edged sword and targeted therapy strategies (Review). Exp. Ther. Med. 2022, 24, 640. [Google Scholar] [CrossRef]
- Gu, Y.; Du, Y.; Jiang, L.; Tang, X.; Li, A.; Zhao, Y.; Lang, Y.; Liu, X.; Liu, J. αvβ3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanoma. J. Nanobiotechnol. 2022, 20, 384. [Google Scholar] [CrossRef]
- Gao, H.; Lao, Y.; Zhang, J.; Ding, B. Dendritic Cell-Derived Exosomes Driven Drug Co-Delivery Biomimetic Nanosystem for Effective Combination of Malignant Melanoma Immunotherapy and Gene Therapy. Drug Des. Devel. Ther. 2023, 17, 2087–2106. [Google Scholar] [CrossRef]
- Naeem, P.; Baumgartner, A.; Ghaderi, N.; Sefat, F.; Alhawamdeh, M.; Heidari, S.; Shahzad, F.; Swaminathan, K.; Akhbari, P.; Isreb, M.; et al. Anticarcinogenic impact of extracellular vesicles (exosomes) from cord blood stem cells in malignant melanoma: A potential biological treatment. J. Cell. Mol. Med. 2023, 27, 222–231. [Google Scholar] [CrossRef] [PubMed]
- Schmidt, J.; Riechers, A.; Stoll, R.; Amann, T.; Fink, F.; Spruss, T.; Gronwald, W.; König, B.; Hellerbrand, C.; Bosserhoff, A.K. Targeting melanoma metastasis and immunosuppression with a new mode of melanoma inhibitory activity (MIA) protein inhibition. PLoS ONE 2012, 7, 37941. [Google Scholar] [CrossRef] [PubMed]
- Bogdahn, U.; Apfel, R.; Hahn, M.; Gerlach, M.; Behl, C.; Hoppe, J.; Martin, R. Autocrine tumor cell growth-inhibiting activities from human malignant melanoma. Cancer Res. 1989, 49, 5358–5363. [Google Scholar] [PubMed]
- Bolovan, L.M.; Ceausu, M.; Stanciu, A.E.; Panait, M.E.; Busca, A.; Hotnog, C.M.; Bleotu, C.; Gales, L.N.; Georgescu, M.T.; Prunoiu, V.M.; et al. Correlation Studies between S100 Protein Level and Soluble MIA or Tissue MelanA and gp100 (HMB45) Expression in Cutaneous Melanoma. J. Pers. Med. 2023, 13, 898. [Google Scholar] [CrossRef] [PubMed]
- Feuerer, L.; Lamm, S.; Henz, I.; Kappelmann-Fenzl, M.; Haferkamp, S.; Meierjohann, S.; Hellerbrand, C.; Kuphal, S.; Bosserhoff, A.K. Role of melanoma inhibitory activity in melanocyte senescence. Pigment. Cell Melanoma Res. 2019, 32, 777–791. [Google Scholar] [CrossRef] [PubMed]
- Alegre, E.; Zubiri, L.; Perez-Gracia, J.L.; González-Cao, M.; Soria, L.; Martín-Algarra, S.; González, A. Circulating melanoma exosomes as diagnostic and prognosis biomarkers. Clin. Chim. Acta 2016, 454, 28–32. [Google Scholar] [CrossRef]
- Sasahira, T.; Kirita, T.; Nishiguchi, Y.; Kurihara, M.; Nakashima, C.; Bosserhoff, A.K.; Kuniyasu, H. A comprehensive expression analysis of the MIA gene family in malignancies: MIA gene family members are novel, useful markers of esophageal, lung, and cervical squamous cell carcinoma. Oncotarget 2016, 7, 31137–31152. [Google Scholar] [CrossRef]
- Li, C.; Liu, J.; Jiang, L.; Xu, J.; Ren, A.; Lin, Y.; Yao, G. The value of melanoma inhibitory activity and LDH with melanoma patients in a Chinese population. Medicine 2021, 100, e24840. [Google Scholar] [CrossRef]
- Odashiro, M.; Hans Filho, G.; Pereira, P.R.; Castro, A.R.; Stief, A.C.; Pontes, E.R.; Odashiro, A.N. Melanoma inhibitory activity in Brazilian patients with cutaneous melanoma. An. Bras. Dermatol. 2015, 90, 327–332. [Google Scholar] [CrossRef]
- Fan, S.; Liu, X.; Wu, Y.; Li, K.; Zhao, X.; Lin, W.; Liu, J. Prognostic Value of Lactate Dehydrogenase, Melanoma Inhibitory Protein, and S-100B Protein in Patients with Malignant Melanoma. Evid. Based Complement Altern. Med. 2022, 2022, 9086540. [Google Scholar] [CrossRef] [PubMed]
- Faries, M.B.; Gupta, R.K.; Ye, X.; Hsueh, E.C.; Morton, D.L. Melanoma-inhibiting activity assay predicts survival in patients receiving a therapeutic cancer vaccine after complete resection of American Joint Committee on Cancer Stage III Melanoma. Ann. Surg. Oncol. 2004, 11, 85–93. [Google Scholar] [CrossRef] [PubMed]
- Gu, Q.H.; Li, D.; Xie, Z.H.; Shen, Q.B. The clinical significance of MIA gene in tumorigenesis of lung cancer. Neoplasma 2020, 67, 660–667. [Google Scholar] [CrossRef] [PubMed]
Melanomas arising in sun-exposed skin | Low CSD melanoma: SSM, low CSD nodular melanoma |
High CSD melanoma: lentigo malignant melanoma, high CSD nodular melanoma | |
Desmoplastic melanoma: most often associated with severely sun-damaged skin | |
Melanomas arising in sun-shielded skin or without known UVR exposure | Spitz melanoma |
Acral melanoma | |
Melanoma arising in congenital nevus | |
Melanoma arising in blue nevus |
Melanocytic Marker | Advantages | Disadvantages |
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S100 |
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HMB-45 |
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Melan A |
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MITF |
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SOX 10 |
|
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NK1/C3 |
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PRAME |
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BRAF V600E |
|
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Gosman, L.M.; Țăpoi, D.-A.; Costache, M. Cutaneous Melanoma: A Review of Multifactorial Pathogenesis, Immunohistochemistry, and Emerging Biomarkers for Early Detection and Management. Int. J. Mol. Sci. 2023, 24, 15881. https://doi.org/10.3390/ijms242115881
Gosman LM, Țăpoi D-A, Costache M. Cutaneous Melanoma: A Review of Multifactorial Pathogenesis, Immunohistochemistry, and Emerging Biomarkers for Early Detection and Management. International Journal of Molecular Sciences. 2023; 24(21):15881. https://doi.org/10.3390/ijms242115881
Chicago/Turabian StyleGosman, Laura Maria, Dana-Antonia Țăpoi, and Mariana Costache. 2023. "Cutaneous Melanoma: A Review of Multifactorial Pathogenesis, Immunohistochemistry, and Emerging Biomarkers for Early Detection and Management" International Journal of Molecular Sciences 24, no. 21: 15881. https://doi.org/10.3390/ijms242115881
APA StyleGosman, L. M., Țăpoi, D.-A., & Costache, M. (2023). Cutaneous Melanoma: A Review of Multifactorial Pathogenesis, Immunohistochemistry, and Emerging Biomarkers for Early Detection and Management. International Journal of Molecular Sciences, 24(21), 15881. https://doi.org/10.3390/ijms242115881