Abstract

To investigate secreted protein acidic and rich in cystein (SPARC) and neural cadherin (NCAD), which are associated with epithelial-mesenchymal transition in primary skin melanoma and nodal metastases and their prognostic impact in melanoma patients. Expression of proteins was assessed by immunochemistry in archival paraffin samples from 103 primary melanoma tumors and 16 nodal metastases. Increased expression of SPARC and NCAD in primary skin melanoma was associated with decreased overall survival, adverse clinicopathological features and particularly with microsatellitosis (SPARC) and ulceration (NCAD). In univariate Cox regression analysis, both biomarkers were significantly associated with the risk of death; the multivariate Cox regression analysis identified no significance. The most important result of our study was that we confirmed the strict correlation between SPARC and NCAD expression and clinicopathological parameters related with melanoma progression, which is a specific clinical equivalent of the molecular mechanisms of epithelial-mesenchymal transition process and confirms its key role in the disease outcome.

Highlights

  • Epithelial–mesenchymal transition taking the form of SPARC and NCAD overexpression is correlated with the presence of classic poor prognostic factors: the presence of lymphangio-invasion, high mitotic rate, ulceration (NCAD) and microsatellitosis (SPARC)

  • Poor prognosis is determined by the parameters of the protein expression – high intensity of SPARC (p = 0.001) and the percentage of SPARC-positive cells

  • Overexpression of NCAD (IRS ≥6) in primary tumor cells reduces overall survival by almost 50% (p < 0.001)

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Summary

Objectives

To investigate secreted protein acidic and rich in cystein (SPARC) and neural cadherin (NCAD), which are associated with epithelial–mesenchymal transition in primary skin melanoma and nodal metastases and their prognostic impact in melanoma patients. The aim of the study was to examine the correlation between the expression of SPARC and NCAD and the main clinicopathological parameters, and to determine their prognostic significance

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