Malignant melanoma: An update

A. Slominski, J. Wortsman, A. J. Carlson, L. Y. Matsuoka, Charles M. Balch, M. C. Mihm

Research output: Contribution to journalArticle

Abstract

Context. The rapidly developing fields of melanoma research are revolutionizing the current concepts on melanoma etiology and pathogenesis and are introducing newer diagnostic techniques and potential therapeutic approaches. Objectives. To present the most current concepts on the etiology and pathogenesis of melanoma and to introduce the recent diagnostic techniques and the potential therapeutic approaches. Methods. Data sources were reports on melanoma published in the English language literature and observations made using specimens available at Harvard University, Johns Hopkins Medical Center, Albany Medical College, Loyola University Medical Center, and University of Tennessee Health Science Center. Results. Studies on melanoma containing chromosomal or genetic evaluation were selected for further analysis. Current clinical and pathologic categories with the reported genetic abnormalities were related to the latest information on pigment biology. The data extracted were used to develop a conceptual framework on the pathogenesis of melanoma; the generated model was then evaluated and used to suggest potential therapeutic approaches. Conclusions. (1) Melanoma is not genetically homogenous, and the existing differences between the pathologic categories, particularly in areas such as type of growth phase (radial vs vertical growth), total vertical dimension, ulceration of primary tumor, and metastatic process, have profound prognostic and therapeutic implications. (2) Chromosomal aberrations and gene mutations are found in sporadic and familial melanomas; among the most important are those affecting the 9p21, which contains the p16 locus, a site known to be critical for normal progression of the cell cycle. Aberrant p16 expression is associated with more aggressive behavior. (3) Melanoma cells possess a remarkable repertoire of biosynthetic capacities represented by the production of hormones, growth factors, and their receptors that may sustain and accelerate tumor development and progression. For example, expression of the tumoral products α-melanocyte-stimulating hormone and adrenocorticotropic hormone is regulated in vitro by ultraviolet light, a known carcinogen. (4) Melanomas differ from other tumors in their intrinsic capability to express melanogenic enzymes with the corresponding structural proteins to actually synthesize melanin. Melanogenesis-related proteins are rapidly entering the clinical arena, being used not only as diagnostic markers, but also as potential targets for melanoma therapy.

Original languageEnglish (US)
Pages (from-to)1295-1306
Number of pages12
JournalArchives of Pathology and Laboratory Medicine
Volume125
Issue number10
StatePublished - 2001
Externally publishedYes

Fingerprint

Melanoma
Vertical Dimension
Melanocyte-Stimulating Hormones
Therapeutics
Neoplasms
Growth Factor Receptors
Information Storage and Retrieval
Melanins
Ultraviolet Rays
Growth
Chromosome Aberrations
Carcinogens
Adrenocorticotropic Hormone
Cell Cycle
Proteins
Language
Hormones
Mutation
Health
Enzymes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology

Cite this

Slominski, A., Wortsman, J., Carlson, A. J., Matsuoka, L. Y., Balch, C. M., & Mihm, M. C. (2001). Malignant melanoma: An update. Archives of Pathology and Laboratory Medicine, 125(10), 1295-1306.

Malignant melanoma : An update. / Slominski, A.; Wortsman, J.; Carlson, A. J.; Matsuoka, L. Y.; Balch, Charles M.; Mihm, M. C.

In: Archives of Pathology and Laboratory Medicine, Vol. 125, No. 10, 2001, p. 1295-1306.

Research output: Contribution to journalArticle

Slominski, A, Wortsman, J, Carlson, AJ, Matsuoka, LY, Balch, CM & Mihm, MC 2001, 'Malignant melanoma: An update', Archives of Pathology and Laboratory Medicine, vol. 125, no. 10, pp. 1295-1306.
Slominski A, Wortsman J, Carlson AJ, Matsuoka LY, Balch CM, Mihm MC. Malignant melanoma: An update. Archives of Pathology and Laboratory Medicine. 2001;125(10):1295-1306.
Slominski, A. ; Wortsman, J. ; Carlson, A. J. ; Matsuoka, L. Y. ; Balch, Charles M. ; Mihm, M. C. / Malignant melanoma : An update. In: Archives of Pathology and Laboratory Medicine. 2001 ; Vol. 125, No. 10. pp. 1295-1306.
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AB - Context. The rapidly developing fields of melanoma research are revolutionizing the current concepts on melanoma etiology and pathogenesis and are introducing newer diagnostic techniques and potential therapeutic approaches. Objectives. To present the most current concepts on the etiology and pathogenesis of melanoma and to introduce the recent diagnostic techniques and the potential therapeutic approaches. Methods. Data sources were reports on melanoma published in the English language literature and observations made using specimens available at Harvard University, Johns Hopkins Medical Center, Albany Medical College, Loyola University Medical Center, and University of Tennessee Health Science Center. Results. Studies on melanoma containing chromosomal or genetic evaluation were selected for further analysis. Current clinical and pathologic categories with the reported genetic abnormalities were related to the latest information on pigment biology. The data extracted were used to develop a conceptual framework on the pathogenesis of melanoma; the generated model was then evaluated and used to suggest potential therapeutic approaches. Conclusions. (1) Melanoma is not genetically homogenous, and the existing differences between the pathologic categories, particularly in areas such as type of growth phase (radial vs vertical growth), total vertical dimension, ulceration of primary tumor, and metastatic process, have profound prognostic and therapeutic implications. (2) Chromosomal aberrations and gene mutations are found in sporadic and familial melanomas; among the most important are those affecting the 9p21, which contains the p16 locus, a site known to be critical for normal progression of the cell cycle. Aberrant p16 expression is associated with more aggressive behavior. (3) Melanoma cells possess a remarkable repertoire of biosynthetic capacities represented by the production of hormones, growth factors, and their receptors that may sustain and accelerate tumor development and progression. For example, expression of the tumoral products α-melanocyte-stimulating hormone and adrenocorticotropic hormone is regulated in vitro by ultraviolet light, a known carcinogen. (4) Melanomas differ from other tumors in their intrinsic capability to express melanogenic enzymes with the corresponding structural proteins to actually synthesize melanin. Melanogenesis-related proteins are rapidly entering the clinical arena, being used not only as diagnostic markers, but also as potential targets for melanoma therapy.

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