Mass spectrometric insights into the protein composition of human cutaneous neurofibromas: comparison of neurofibromas with the overlying skin

Abstract

Background: Cutaneous neurofibromas (cNFs) are the hallmark of the tumor-predisposition syndrome neurofibromatosis 1 (NF1). While cNFs are always benign, they markedly decrease quality of life in individuals with NF1. Understanding the differences between cNFs and the skin is essential for developing treatments for cNFs.

Methods: We collected 15 cNFs from four NF1 individuals and used mass spectrometry to compare the tumor tissue with the skin overlying each tumor. Data were analyzed based on Gene Ontology (GO) terms.

Results: The expression patterns of the Schwann cell marker S100B and several keratins confirmed successful dissection of cNF tissue from the overlying skin. Hierarchical clustering showed extensive overlap between the tumor and skin samples in three out of four individuals, suggesting high overall similarity between the two tissue types. Based on the analysis of the GO terms, cNFs were associated with decreased expression of proteins related to cell proliferation, extracellular matrix remodeling, angiogenesis and cellular metabolism.

Conclusion: The cNFs are relatively quiescent, consistent with their benign nature and limited growth potential. The development of pharmacological therapy for cNFs requires overcoming the high similarity between cNFs and the overlying skin. The present dataset can serve as a resource for future research on cNFs.

Fig. 1. Hierarchical clustering of cutaneous neurofibromas and the overlying skin based on protein quantities.

The top row shows results of individual-wise clustering, and the bottom panel displays pooled clustering of all the samples. In the dendrograms, tumor samples are highlighted in blue, and skin samples in orange. In the lower panel, each individual is denoted with a unique symbol in the dendrogram.

Fig. 2. Hematoxylin-eosin staining and immunohistochemical labeling for the cell proliferation marker Ki67, and collagens XV (ColXV) and XVIII (ColXVIII) of a representative cutaneous neurofibroma.

A total of 20 cutaneous neurofibromas from seven NF1 patients were examined. Proliferating cells are sparse within the tumor compared with the overlying skin whereas ColXV and ColXVIII are predominantly expressed in the tumor tissue. Scale bars 1 mm in the first column, 200 µm in the second column.