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Multi-photon Imaging of Tumor Cell Invasion in an Orthotopic Mouse Model of Oral Squamous Cell Carcinoma
Published on: July 25, 2011
Identification of new head and neck squamous cell carcinoma molecular imaging targets
Jeroen E van Schaik1, Bert van der Vegt2, Lorian Slagter-Menkema3
1Department of Otorhinolaryngology, Head and Neck Surgery, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.
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.
Insights
New imaging targets for head and neck squamous cell carcinoma (HNSCC) fluorescence imaging (FI) were identified. Glucose transporter-1 (GLUT-1) and P-cadherin showed higher expression than EGFR, suggesting their potential for improved HNSCC detection.
Area of Science:
- Oncology
- Surgical Imaging
- Molecular Diagnostics
Background:
- Intraoperative fluorescence imaging (FI) aids in identifying head and neck squamous cell carcinoma (HNSCC) margins.
- Current reliance on epidermal growth factor receptor (EGFR) for FI can lead to non-specific tracer accumulation in normal tissues.
- There is a need for more specific molecular targets for HNSCC FI.
Purpose of the Study:
- To identify novel molecular targets for HNSCC intraoperative fluorescence imaging.
- To evaluate potential new targets against the current standard, EGFR.
Main Methods:
- Transcriptomic data from HNSCC and healthy oral mucosa were analyzed using Transcriptional Adaptation to Copy Number Alterations (TACNA)-profiling.
- Potential targets were selected based on overexpression and plasma membrane expression.
- Immunohistochemistry was used to validate target expression on patient biopsies, comparing them to EGFR.
Main Results:
- TACNA-profiling identified glucose transporter-1 (GLUT-1), P-cadherin, monocarboxylate transporter-1 (MCT-1), and neural/glial antigen-2 (NG2) as potential HNSCC targets.
- Immunohistochemical analysis confirmed high expression of GLUT-1 (100%) and P-cadherin (100%) in HNSCC tumors.
- Both GLUT-1 and P-cadherin demonstrated significantly higher expression levels compared to EGFR in HNSCC samples.
Conclusions:
- The study successfully identified GLUT-1 and P-cadherin as promising novel targets for HNSCC fluorescence imaging.
- These targets exhibit superior expression in HNSCC compared to EGFR, suggesting improved specificity and efficacy for intraoperative margin assessment.
- Further investigation into GLUT-1 and P-cadherin for HNSCC FI is warranted.
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