Expression profiles associated with aggressive behavior in Merkel cell carcinoma

Abstract

Primary neuroendocrine carcinoma of the skin, or Merkel cell carcinoma, is the most aggressive cutaneous neoplasm. In spite of its similarities to small cell carcinomas from other locations, Merkel cell carcinoma shows many peculiarities probably related to its epidermal origin and the etiologic role of UV radiation. We have immunohistochemically investigated 43 markers on a tissue microarray in which 31 surgically resected Merkel cell carcinomas were represented. Of these, 15 patients remained free of disease after removal, whereas 16 developed metastases. Immunoreactivity was scored according to staining intensity and the percentage of positive cells. We found statistically significant correlations between metastatic tumor spread and overexpression of matrix metalloproteinase (MMP) 7, MMP10/2, tissue inhibitor of metalloproteinase 3, vascular endothelial growth factor (VEGF), P38, stromal NF-kappaB, and synaptophysin. Also detected were statistically significant correlations between the expression levels of MMP7 and VEGF, MMP7 and P21, MMP7 and P38, MMP10/2 and VEGF, P38 and synaptophysin, P38 and P53, and P21 and stromal NF-kappaB. These findings may be helpful in predicting the clinical course of Merkel cell carcinoma and are potentially useful for the development of targeted therapies.

Silent mutations in KIT and PDGFRA and coexpression of receptors with SCF and PDGFA in Merkel cell carcinoma: implications for tyrosine kinase-based tumorigenesis

“…In our study of Merkel cell carcinoma, we observed diffuse and weak expression of VEGF in 480% of cases (unpublished data), which is similar to data recently published examining 43 markers on 31 cases of Merkel cell carcinoma via tissue microarray analysis. 49 However, the staining we observed for VEGF was independent of KIT expression levels, suggesting that multiple pathways may exist which activate VEGF expression. The data of Fernandez-Figueras et al 49 also suggests a likely role for VEGF in tumor progression and the potential benefit of using anticancer treatments targeted against VEGF and other members of its signaling pathway.…”

Evidence for distinct populations of human Merkel cells

“…Our results conWrm data presented by Garcia-Caballero and colleagues (1989) who described the presence of synaptophysin in MCs of the pig snout. Interestingly, synaptophysin was also detected in a large proportion of MCC (Acebo et al 2005;Fernandez-Figueras et al 2007;Llombart et al 2005).…”

Merkel cell carcinoma

“…The frequent heterozygous loss of chromosome 10 or the long arm of chromosome 10 in MCC suggests that the tumor suppressor PTEN encoded there plays a relevant role [37]. A recent study using MCC tissue arrays to measure the expression of various proteins (especially matrix metalloproteinases) revealed that PTEN could hardly be identified in the samples examined, which could indicate inactivation of the second allele, e.g., by epigenetic mechanisms [38]. The epigenetic silencing of another tumor suppressor gene in MCC had been recently reported [39].…”