Identification of new head and neck squamous cell carcinoma molecular imaging targets

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van Schaik JE, van der Vegt B, Slagter-Menkema L, van der Laan BFAM, Witjes MJH, Oosting SF, Fehrmann RSN, Plaat BEC

Objectives: Intraoperative fluorescence imaging (FI) of head and neck squamous cell carcinoma (HNSCC) is performed to identify tumour-positive surgical margins, currently using epidermal growth factor receptor (EGFR) as imaging target. EGFR, not exclusively present in HNSCC, may result in non-specific tracer accumulation in normal tissues. We aimed to identify new potential HNSCC FI targets.

Materials and methods: Publicly available transcriptomic data were collected, and a biostatistical method (Transcriptional Adaptation to Copy Number Alterations (TACNA)-profiling) was applied. TACNA-profiling captures downstream effects of CNAs on mRNA levels, which may translate to protein-level overexpression. Overexpressed genes were identified by comparing HNSCC versus healthy oral mucosa. Potential targets, selected based on overexpression and plasma membrane expression, were immunohistochemically stained. Expression was compared to EGFR on paired biopsies of HNSCC, adjacent macroscopically suspicious mucosa, and healthy mucosa.

Results: TACNA-profiling was applied on 111 healthy oral mucosa and 410 HNSCC samples, comparing expression levels of 19,635 genes. The newly identified targets were glucose transporter-1 (GLUT-1), placental cadherin (P-cadherin), monocarboxylate transporter-1 (MCT-1), and neural/glial antigen-2 (NG2), and were evaluated by IHC on samples of 31 patients. GLUT-1 was expressed in 100 % (median; range: 60-100 %) of tumour cells, P-cadherin in 100 % (50-100 %), EGFR in 70 % (0-100 %), MCT-1 in 30 % (0-100 %), and NG2 in 10 % (0-70 %). GLUT-1 and P-cadherin showed higher expression than EGFR (p < 0.001 and p = 0.015).

Conclusions: The immunohistochemical confirmation of TACNA-profiling results showed significantly higher GLUT-1 and P-cadherin expression than EGFR, warranting further investigation as HNSCC FI targets.