Abstract 899P
Background
Laryngeal squamous cell carcinoma (LSCC) is associated with 20-50% recurrence rate after definitive chemoradiation. The primary purpose of this study is to explore transcriptomic changes that occur in primary and recurrent laryngeal tumors in order to determine new genetic targets underpinning the development and recurrence of LSCC.
Methods
A total of 73 fresh-frozen paraffin-embedded tissue samples were obtained from 10 patients with recurrent laryngeal tumors. Each patient had at least 2 anatomic areas sampled. Samples were classified as normal adjacent tissue, primary tumor or recurrent tumor. Clariom D gene expression microarray analysis was to generate whole-transcriptome gene profiles. Validation was performed utilizing a previously published dataset of LSCC.
Results
One hundred and eight probes representing 58 unique genes were differentially expressed comparing normal tissue to tumor tissue of any type. These genes play roles in various pathways including developmental biology, cell junction organization and programmed cell death (27% were validated.) When comparing normal tissue to primary tumors, 34 genes were differentially expressed. These were associated with cornified envelope, developmental biology (26% were validated). Seventy-seven unique genes were identified when comparing normal tissue to recurrent tumor, 28% of which were validated. These genes were associated with integrin interaction, developmental biology and the MET pathway. Three genes, MT2A, MIR4521 and SNORD3A were differentially expressed when comparing primary to recurrent tumors. Twenty-four genes were differentially expressed when comparing normal tissue to primary and recurrent tumor, individually. Several of these have been associated with head and neck cancer while others have been associated with thyroid cancer.
Conclusions
Primary and recurrent laryngeal tumors share genetic alterations associated with the disruption of cellular differentiation based on transcriptome-wide assays. Further exploration of the tumor microenvironment and its associated genes in the pre-treatment and paired salvage setting may lead to better understanding of the molecular mechanism of treatment resistance within laryngeal cancers.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Ohio State University - charitable donations.
Disclosure
All authors have declared no conflicts of interest.