Relationship of Tumorigenic Malignant Melanomas to Dermal Elastin

Abstract

Malignant melanomas, which produce a large number of substances active in connective tissue modulation, must contend with the dermis to grow and propagate. We studied the morphologic interactions between tumorigenic malignant melanomas and dermal elastin. Formalin-fixed and paraffin-embedded tissues of 108 tumorigenic malignant melanomas were stained for elastic tissue with the Verhoeff-van Gieson method. Various aspects of the relationship between malignant melanoma and dermal elastin were analyzed in relation to the histologic and clinical data using univariate and multivariate analyses. Tumor thickness, mitotic rate, and the presence of elastin remnants within the tumors were found to be independent negative prognostic factors, the latter with borderline significance. Tumors with more remnants of elastin were associated with higher stage of disease and lymph node and distant metastases. Tumor infiltration between the elastic fibers in the tumor depth was associated with high Clark level, greater tumor thickness, high stage of disease, and lymph node metastases. At least partial preservation of elastic fibers in the tumor depth was a relatively good prognostic factor whereas complete absence of elastin was an adverse factor. Focal or multifocal absence of elastin in the midst of the tumors or in their depth was usually associated with lymphocytic infiltrates. We suggest that tumors with remnants of elastic fibers and/or invasion between elastic fibers in their depth may be fast growing and highly invasive. The absence of elastin within tumors and at their advancing edge may be related to the elaboration of elastin-degrading substances by melanoma cells or various inflammatory cells. Our findings indicate that the relationship between malignant melanomas and dermal connective tissue components, specifically elastin, may have prognostic significance.

Elastin-derived peptides enhance melanoma growth in vivo by upregulating the activation of Mcol-A (MMP-1) collagenase

“…Previous in vitro studies suggesting that the stromal reaction induced by EDPs could promote collagen degradation through collagenase production (Brassart et al , 2001) supports this view. This could explain the histopathological data underlining a strong correlation between elastin fragmentation and melanoma aggressiveness (Breslow, 1970; Feinmesser et al , 2002). Moreover, it was proposed that EDPs could act as factors promoting the transition between melanoma radial growth phase to vertical growth phase in which melanoma cells infiltrate and invade the dermis.…”

“…It was suggested that partial preservation of elastic fibres in the tumour depth was a relatively good predictive factor, whereas complete absence of elastin was an adverse one (Feinmesser et al , 2002). However, this study was based on histological analyses and no in vivo studies were carried out to confirm this hypothesis.…”