The immunohistochemistry of invasive and proliferative phenotype switching in melanoma: A case report

Ossia M. Eichhoff, Marie C. Zipser, Mai Xu, Ashani T. Weeraratna, Daniela Mihic, Reinhard Dummer, Keith S. Hoek

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


To date there is no effective therapy for metastatic melanoma and at the molecular level the disease progression is poorly understood. A recent study by our group led to the development of a novel phenotype switching model for melanoma progression, wherein cells transition back-and-forth between states of proliferation and invasion to drive disease progression. To explore the model's clinical relevance we interrogated phenotype-specific expression patterns in human melanoma patient material. A matched primary/metastasis pair from a human melanoma patient was obtained and immunohistochemically stained for proliferative and invasive phenotype markers. These were also stained for hypoxia and blood vessel markers. Proliferative phenotype markers Melan-A and Mitf showed consistent anti-correlation with invasive phenotype marker Wnt5A and hypoxia marker Glut-1. These also correlated with observed intra-tumoural vascularization patterns. Similar pattern distributions were present in both primary and metastasis samples. Strikingly, we observed that late phase metastatic melanoma cells adopt morphologies and behaviours identical to very early phase cells. The expression patterns observed closely matched expectations derived from previous in vitro and xenografting experiments. These results highlight the likelihood that disease progression involves melanoma cells retaining the capacity to regulate the expression of metastatic potential critical factors according to changing microenviron mental conditions.

Original languageEnglish (US)
Pages (from-to)349-355
Number of pages7
JournalMelanoma Research
Issue number4
StatePublished - Aug 2010
Externally publishedYes


  • immunohistochemistry
  • melanoma
  • phenotype switching

ASJC Scopus subject areas

  • Oncology
  • Dermatology
  • Cancer Research


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