The melanomas: a heterogeneous group
Friday November 25, 2011
The melanomas: a synthesis of epidemiological, clinical, histopathological, genetic, and biological aspects, supporting distinct subtypes, causal pathways, and cells of origin
A comprehensive review article published in Pigment Cell and Melanoma Research outlines the historical developments that underpin the understanding of melanoma heterogeneity, provides current evidence to classify the distinct subtypes and concludes with important unanswered questions.
As the authors highlight in the abstract, “understanding the relationships of each subtype of melanoma with etiologic factors such as UV radiation and constitutional factors is the first necessary step toward developing refined prevention strategies for the specific forms of melanoma”. Also, classifying melanoma into biological distinct subtypes “is the key to developing mechanism-based treatments”.
The authors offer a multidisciplinary approach, which includes epidemiological, clinical, histopathological, genetic and biological aspects, with each addressed separately. For example, the epidemiological section describes the studies that first identified the relationship between sunlight and melanoma, along with more recent findings in relation to anatomic distribution and insights from comparisons of occupational groups. According to the authors, the latter provided the first epidemiological evidence that melanomas arising on different body sites may be associated with sunlight in different ways. In summarising this section, the authors conclude that the data “make a compelling case that different subtypes of cutaneous melanoma may be defined through different combinations of causal factors operating at different times in the evolution of the cancer”.
A section on molecular aspects then “extends this concept of heterogeneity by exploring whether the pathways to melanoma might be reflected in disruptions to molecules that control critical functions within the pigment cell”. A subsequent section then offers clues to melanoma diversity from melanocyte development.
The final section provides a synthesis of the emerging subtypes of melanoma and describes the divergent pathway hypothesis, with one determinant of melanoma development being the propensity of the host to develop nevi. The authors then make the distinction between melanomas arising from epithelial melanocytes from those arising from melanocytes not associated with epithelia, such as uveal melanomas.
In their conclusion, the authors argue that ‘because of the striking differences between some of the subtypes, it appears obvious that they have to be regarded separately when considering guidelines or recommendations for prevention, therapy and prognostication of melanoma, as what may apply to one type may not for the other”. In their view, ‘this effect has been highlighted by the advent of molecularly targeted therapy but is clearly not restricted to this area. Most, if not all, current treatment guidelines are formulated for melanoma as if it were a single disease entity.” The authors conclude that many important questions remain unanswered.
Source:
Whiteman DC, William J. Pavan WJ, Bastian BC. The melanomas: a synthesis of epidemiological, clinical, histopathological, genetic, and biological aspects, supporting distinct subtypes, causal pathways, and cells of origin. (2011)
Pigment Cell Melanoma Res. 24; 879–897
doi: 10.1111/j.1755-148X.2011.00880.x
http://onlinelibrary.wiley.com/doi/10.1111/j.1755-148X.2011.00880.x/abstract
(The full article is freely available on-line.)
