Abstract 3349: Immunoexpression of human melanoma stem markers during progressive stages of the disease
Authors: Sharma Bhuvnesh K. , Hasskamp Joanne H. , Manglik Vinod , Zapas John L. , Elias Elias George 
Published: February 2011

Introduction: Human Cutaneous melanoma is known as potentially lethal malignancy due to its inherent intrinsic resistance to various cancer therapeutic modalities. Ineffective chemotherapy may be linked to the existence of hyperpolarized CD133+ subpopulation of melanoma stem cells. Recently, this subpopulation has been shown to express a novel chemoresistance mediator ABCB5+ thus acquire aggressive and resistant cell phenotype to cancer therapy. The present exploratory study was undertaken to identify preferential expression of melanoma stem cell markers-CD133+ and ABCB5+ as well as their anchoring adhesion molecule CD166 and Nestin- a neural stem cell marker to define high risk population.

Methods: 5µm thick paraffin embedded tissue sections from primary melanoma (n=40), lymph node (LN) metastasis (n=15), distant metastatic lesions (n=19), benign melanocytic nevi (n=11) were subjected for immunohistochemical staining for melanoma stem makers using monoclonal antibodies to CD133+, ABCB5, CD166 and Nestin. In addition, archival tissue sections were also included from patients with primary melanoma who had short disease-free survival (DFS) and developed metastasis within 6 months (n=8),as well as disease those with longer DFS of &gt;24 months (n=13) in order to correlate expression of melanoma stem cell markers with different clinical outcome.

Results: Using Fisher's exact test, the statistical analysis revealed significant difference in overexpression of ABCB5+ and CD133 stem cell markers in distant metastatic lesions compared to benign melanocytic nevi (p&lt;0.007 and p&lt;0.05 respectively). In addition, significant overexpression of the adhesion molecule- CD166 was found in primary melanoma compared with benign nevi (p&lt;0.0012). Simultaneous overexpression of CD133+/ABCB5+ was also observed statistically significant in Lymph node and distant metastases (p&lt;0.002 and p&lt;0.026 respectively) when compared to benign nevi. Two cases of benign nevi that expressed ABCB5+ and CD133+ markers belonged to patients who had past history of melanoma. Greater percentage of cases of primary melanoma who had short DFS demonstrated overexpression of ABCB5+ compared to those who had longer DFS. However, they did not reach statistical significance probably due to the limited number of study cases. Furthermore, no significant difference in immunoexpression of all stem cell markers was observed in primary melanoma compared to distant metastases.

Conclusions: CD133 stem cell population exhibiting chemoresistance mediator ABCB5+ may be distinct aggressive phenotypes of invasion and metastases which are uniquely associated with human cutaneous melanoma. These findings may have further diagnostic and therapeutic implication.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3349.