Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Pathology

Supervisor

Darling, Mark

2nd Supervisor

Khan, Zia

Joint Supervisor

3rd Supervisor

Lapointe, Henry

Co-Supervisor

Abstract

Granular Cell Tumours (GCTs) are rare subepithelial lesions that are believed to develop from Schwann cells and are characterized by large polygonal cells with abundant lysosomes. Pilot studies from our laboratory showing unexpected HLA-DR immunoreactivity in GCTs lead us to hypothesize that GCTs have an antigen presenting cell (APC) phenotype.

To test our hypothesis, we assessed immunoreactivity of GCT lesions to APC phenotype markers, including CD68, HLA-DR, CD163, CD40 and CD11c. In addition, we assessed markers of neural crest cell (NCC) origin S100, SOX10, NSE and GAP43. Samples subjected to these studies included 23 cases of GCTs and 10 cases of Schwannomas, used as comparators. To confirm the key findings, we detected transcript levels of select genes using quantitative polymerase chain reaction.

We identified a new NCC marker for GCTs, GAP43. We also provide evidence of an APC phenotype of GCTs, as determined from CD68 and HLA-DR immunoreactivity. Due to the limited nucleic acid yield from paraffin-embedded GCT sections, we were unable to draw conclusions from transcript assessment.

Summary for Lay Audience

Granular Cell tumours (GCT) are rare benign nodular lesions that develop in the connective tissue below the skin. Our current understanding is that these tumours develop from tissue-supporting cell types called Schwann cells. Schwann cells support the peripheral nervous system. Based on pilot work completed in our lab, GCTs appear express a protein that is commonly found on immune cells. Based on these studies, we hypothesized that the cells making up GCTs have a cellular appearance or behaviour similar to cells in the body whose job is to identify foreign material, such as bacteria or viruses. To test our hypothesis, we obtained tumour tissues and examined whether these tissues express other proteins that would strengthen an immune cell-like property. We were able to identify one additional protein that is primarily found in immune cells: CD68. A panel of other proteins tested were not found. While there are similarities in the appearance of the granular cells and immune cells, the evidence is not conclusive. One key finding, however, is that GCTs express a new protein called GAP43 which is important in the growth of new nerves and is found in Schwann cells following nerve injury. The presence of GAP43 protein in the granular cells of GCTs provides strong evidence that GCTs develop from Schwann cells. Future studies from our lab will focus on whether granular cells are more like mature or immature Schwann cells.

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

Download

Share

COinS