What Does Ulceration of a Melanoma Mean for Prognosis?

Ulceration as negative prognostic factor

Ulceration was first identified as a negative prognostic factor in cutaneous melanoma by Allen and Spitz [2] and Tompkins [3] in 1953. Throughout the subsequent three decades, many other groups corroborated this finding [4], [5], [6]. However, thickness of the primary tumor is also a key prognostic factor in melanoma, and the presence of ulceration strongly correlates with thickness of the primary tumor. For example, in a study of 250 patients with cutaneous melanoma, the incidence of

Ulceration as predictor of sentinel lymph node involvement

Sentinel lymph node (SLN) status has been shown to be the most important single factor that predicts survival in patients with melanoma: patients with SLN-positive melanoma are 6.5 times more likely to die from melanoma than patients with negative nodes [13]. Several groups have looked specifically at the question of which factors independently predict SLN involvement by tumor; ulceration has been identified as an independent predictor of positive SLN biopsy [14], [15], [16].

Several years ago,

Ulceration as predictor of response to adjuvant IFN therapy

Our group recently used data from the Sunbelt Melanoma Trial to explore the relationship between the presence of ulceration and response to adjuvant IFN therapy in cutaneous melanoma [18].

By way of background, IFN is the only Food and Drug Administration–approved adjuvant therapy for melanoma patients at high risk for disease recurrence. IFN was initially approved by the Food and Drug Administration in this setting because of the results of the Eastern Cooperative Oncology Group (ECOG)

Ulceration and underlying molecular mechanisms

The mechanisms underlying the prognostic significance of ulceration remain poorly understood. The two most well-founded hypotheses include the idea that ulceration is a surrogate for underlying molecular features of the tumor or the host that favors aggressive behavior, or that ulceration itself directly leads to early tumor dissemination, perhaps by alterations in the local environment [25].

There are some data to support ulceration as a phenotypic expression of unfavorable genetics and

Summary

Ulceration of a primary cutaneous melanoma is clearly associated with worse prognosis, although the underlying mechanisms are not well understood. Recent studies have shown that the presence of ulceration may predict response to adjuvant IFN in high-risk patients. As molecular pathways continue to be elucidated, it is possible that continued study of ulceration will provide insight into potential therapeutic strategies, or will predict response to novel targeted therapies. Future investigation