Abstract
BackgroundPatients with head and neck squamous cell carcinoma (HNSCC) can develop lung squamous cell carcinoma (LuSCC), which could be the second primary tumor or HNSCC metastasis. Morphologically it is difficult to distinguish metastatic HNSCC from a second primary tumor which presents a significant diagnostic challenge. Differentiation of those two malignancies is important because the recommended treatments for metastatic HNSCC and primary LuSCC differ significantly. We investigated if the quantification of the promotor methylation status in HNSCC and LuSCC differs.MethodsPrimary HNSCC (N = 36) and LuSCC (N = 17) were included in this study. Methylation status in the ASC/TMS1/PYCARD (apoptosis-associated speck-like protein containing a caspase recruitment domain; 8 CpG sites) and MyD88 (Myeloid differentiation primary response protein 88; 10 CpG sites) promoters was analyzed. Bisulfite converted DNA, isolated from tumor tissue was quantified using pyrosequencing. Results of pyrosequencing analysis were expressed as a percentage for each tested CpG site. Receiver-operating characteristic (ROC) curve analysis was used for the evaluation of the diagnostic properties of selected biomarkers.ResultsCpG sites located in the promoters of ASC/TMS1/PYCARD_CpG8 (− 65 upstream) and MyD88_CpG4 (− 278 upstream) are significantly hypermethylated in the HNSCC when compared with LuSCC (p ≤ 0.0001). By performing ROC curve analysis we showed that corresponding areas under the curve (AUC) were 85–95%, indicating that selected CpG sites are useful for a distinction between primary LuSCC and primary HNSCC.ConclusionsResults of the present study indicate that there is a significant difference in the methylation status of tested genes between primary HNSCC and LuSCC. However, to prove this approach as a useful tool for distinguishing second primary LuSCC from HNSCC metastasis, it would be necessary to include a larger number of samples, and most importantly, metastatic samples.
Highlights
Patients diagnosed with head and neck squamous cell carcinoma (HNSCC) can present with lung metastases, or develop second primary lung tumors [1]
Results of the present study indicate that there is a significant difference in the methylation status of tested genes between primary HNSCC and lung squamous cell carcinoma (LuSCC)
We found that the methylation status of tested genes in tumor tissue could be used as a potential prognostic biomarker in patients with early-stage non-small cell lung cancer (NSCLC) because hypomethylation of specific CpG sites in ASC/TMS1/PYCARD gene was associated with reduced overall survival
Summary
Patients diagnosed with head and neck squamous cell carcinoma (HNSCC) can present with lung metastases, or develop second primary lung tumors [1]. Solitary lung nodule could represent lung metastasis or primary lung carcinoma [3] Given their morphologic similarities, lung metastases and primary squamous cell carcinoma of the lung (LuSCC) cannot be distinguished based on histopathologic characteristics. It is difficult to distinguish metastatic HNSCC from a second primary tumor which presents a significant diagnostic challenge. Differentiation of those two malignancies is important because the recommended treatments for metastatic HNSCC and primary LuSCC differ significantly. We investigated if the quantification of the promotor methylation status in HNSCC and LuSCC differs
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