Loss of E-cadherin as Part of a Migratory Phenotype in Melanoma Is Associated With Ulceration.

Autor: Bønnelykke-Behrndtz ML; Departments of *Oncology, and †Pathology, Aarhus University Hospital, Aarhus, Denmark; ‡Plastic Surgery Research Unit, Department of Plastic Surgery, Aarhus University Hospital, Aarhus, Denmark; §Department of Pathology, Herlev Hospital, Herlev, Denmark; ¶Department of Gastrointestinal Medicine, Hvidovre Hospital, Hvidovre; ‖Department of Oncology, Odense University Hospital, Odense, Denmark; and **Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark., Steiniche T, Nørgaard P, Danielsen AV, Damsgaard TE, Christensen IJ, Bastholt L, Møller HJ, Schmidt H
Jazyk: angličtina
Zdroj: The American Journal of dermatopathology [Am J Dermatopathol] 2017 Sep; Vol. 39 (9), pp. 672-678.
DOI: 10.1097/DAD.0000000000000750
Abstrakt: It has been suggested that embryogenic properties of migratory cells are reactivated during wound healing and metastasis in adults. This might explain the association between wound-induced inflammation and poor survival in patients with ulcerated melanoma. Linking inflammation with a migratory phenotype, we characterize the infiltration of innate inflammatory cells, loss of cell-to-cell adhesion (E-cadherin), factors associated with extracellular matrix degradation [matrix metalloproteinase-9 (MMP-9), and neutrophil elastase (NE)], and spindle-shaped cell morphology, between ulcerated (n = 179) and nonulcerated (n = 206) melanoma. In addition, the presence of "extravascular migratory metastasis" (angiotropism) and tumor-vessel density were evaluated as important factors for tumor cell dispersal in ulcerated melanoma. We showed a correlation between expression of the granulocyte marker cd66b+ and the expression of NE and MMP-9, reflecting activated neutrophils. Ulcerated melanoma correlated with a low global E-cadherin score (P = 0.041) and weak-spot score (P = 0.0004). Thus, 28% of the nonulcerated, 42% of the minimally/moderately ulcerated melanoma, and 53% of the excessively ulcerated melanoma presented low scores as opposed to a high E-cadherin score. In addition, the presence of ulceration was correlated with angiotropism (P < 0.0001) and spindle-shaped morphology (P = 0.021). There were no differences in MMP-9 expression or intratumoral vessel density between the ulcerated and nonulcerated group. In conclusion, expression of migratory cell properties showed a highly heterogeneous pattern, which was associated with ulcerated areas and inflammatory cells, in general and with neutrophils in particular. We, therefore, suggest that wound-associated inflammation may be involved in the induction of migratory cell transition and tumor cell dispersal in ulcerated melanoma.
Databáze: MEDLINE