Loss of microRNA-200a and c, and microRNA-203 expression at the invasive front of primary cutaneous melanoma is associated with increased thickness and disease progression

van Kempen, L. C., van den Hurk, K., Lazar, V., Michiels, S., Winnepenninckx, V., Stas, M., Spatz, A. & van den Oord, J. J., 2012, In : Virchows Archiv : an International Journal of Pathology. 461, 4, p. 441-8 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Léon C van Kempen
  • Karin van den Hurk
  • Vladimir Lazar
  • Stefan Michiels
  • Véronique Winnepenninckx
  • Marguerite Stas
  • Alan Spatz
  • Joost J van den Oord

Loss of E-cadherin expression in melanoma correlates with increased tumor thickness and reduced disease-free survival. The molecular mechanisms underpinning its differential expression in melanoma tissue remain elusive. MicroRNAs (miRNAs) have been implicated in tumor progression and regulation of E-cadherin expression. Here, we demonstrate a significant correlation between tumor thickness and loss of expression of miR-200a, miR-200c, and miR-203 in a series of 23 frozen primary melanomas, where it was confirmed in two subsequent validation series (series 1: six nevi, 15 primary melanomas, and 16 metastases; series 2: 11 matched pairs of primary melanomas and metastases). Decreased levels of miR-200a, miR-200c, and miR-203 correlated with increasing thickness in the combined validation series (P = 0.024, 0.033, and 0.031, respectively). In addition, progressive loss of miR-200a expression with disease progression was observed in series 1 (P < 0.001) and in series 2 (P = 0.029). MiR-200 in situ hybridization and E-cadherin immunohistochemistry demonstrated reduced expression of both at the deep invasive margin of the tumor. Furthermore, a functional validation study using an anti-miR200 strategy demonstrated that loss of miR-200 expression in melanoma cell lines reduced E-cadherin expression. Collectively, our data point towards an important role for miR-200 and miR203 expression in regulating E-cadherin during melanoma progression.

Original languageEnglish
Pages (from-to)441-8
Number of pages8
JournalVirchows Archiv : an International Journal of Pathology
Issue number4
Publication statusPublished - 2012


  • Biomarkers, Tumor/genetics, Cadherins/genetics, Disease Progression, Down-Regulation, Gene Expression Regulation, Neoplastic, Humans, Melanoma/diagnosis, MicroRNAs/genetics, Predictive Value of Tests, Prognosis, Retrospective Studies, Skin Neoplasms/diagnosis

ID: 118614305