One of the common malignant tumors of the head and neck worldwide with generally unfavorable prognosis is squamous cell carcinoma (OSCC) of the oral cavity. Early detection of primary, secondary, or recurrent OSCC by liquid biopsy tools is much needed.
Twelve blood biomarkers were used for monitoring a case of OSCC suffering from precancerous oral lichen ruber planus mucosae (OLP). After curative R0 tumor resection of primary OSCC (buccal mucosa), elevated epitope detection in monocytes (EDIM)-Apo10, EDIM-transketolase-like-1 (TKTL1), squamous cell carcinoma antigen (SCC-Ag), total serum lactate dehydrogenase (LDH), and its anaerobic isoforms (LDH-4, LDH-5) decreased to normal levels. Three and six months after surgery, transformation of suspicious mucosal lesions has been accompanied with an increase of EDIM scores, total serum LDH values, and a metabolic shift from aerobic (decrease of LDH-1, LDH-2) to anaerobic (increase of LDH-4, LDH-5) conditions. Two months later, secondary OSCC was histopathologically analyzed after tissue biopsy. Cytokeratin fraction 21-1 (CYFRA 21-1), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) were not affected during the clinical course of carcinogenesis.
A combination strategy using a standardized panel of established (metabolic) blood biomarkers (TKTL1, LDH, LDH isoenzymes) is worth and can be recommended among others (apoptosis resistance-related Apo10, SCC-Ag) for early detection and diagnosis of primary, secondary, and recurrent OSCC. A tandem strategy utilizing (metabolic pronounced) routine liquid biopsies with imaging techniques may enhance diagnosis of OSCC in the future. Although we demonstrated the diagnostic utility of separated liquid biopsies in our previous study cohorts, further investigations in a larger patient cohort are necessary to recommend this combination strategy (EDIM blood test, LDH value, metabolic shift of LDH isoenzymes, and others, e.g., SCC-Ag or immunophenotyping) as a diagnostic tool for the addition to the OSCC staging system and as a routine procedure in the aftercare.
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oral squamous cell carcinoma
epitope detection in monocytes
squamous cell carcinoma antigen
- CYFRA 21-1:
cyotokeratin fraction 21–-1
Hematoxylin and Eosin
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We thank biovis’ Diagnostik MVZ especially Melanie Hügen and Martina Thümmler for the technical support.
MG, SH, and MK performed follow-up of the patient and were major contributors in conducting, writing, and revising the manuscript. TB and MG evaluated the immunohistology and immunohistochemistry slides. OF performed the flow cytometric analysis. PT and SR conceived the study and drafted the manuscript. All authors read and approved the final manuscript.
Written informed consent to participate was obtained prospectively from the patient (Ethics Committee Tuebingen, Germany, approval number: 562-2013BO2).
OF is an employee and shareholder of Zyagnum AG, Frankfurt am Main, Germany, and declares a potential conflict of interest due to the possible utilization of Apo10 and TKTL1 for diagnostic and/or therapeutic purposes. The authors have no other affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
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Grimm, M., Hoefert, S., Krimmel, M. et al. Monitoring carcinogenesis in a case of oral squamous cell carcinoma using a panel of new metabolic blood biomarkers as liquid biopsies. Oral Maxillofac Surg 20, 295–302 (2016). https://doi.org/10.1007/s10006-016-0549-2
- Lactate dehydrogenase
- Squamous cell carcinoma antigen
- Cytokeratin fraction 21-1
- Epitope detection in monocytes (EDIM) technology
- Oral squamous cell carcinoma