RESUMO
BACKGROUND: Patients 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. METHODS: Primary 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. RESULTS: CpG 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. CONCLUSIONS: Results 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.
Assuntos
Ilhas de CpG/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias de Cabeça e Pescoço/genética , Fator 88 de Diferenciação Mieloide/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Idoso , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Epigênese Genética/genética , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Fator 88 de Diferenciação Mieloide/metabolismo , Regiões Promotoras Genéticas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
Neuroendocrine tumors (NET) of the larynx are rare and heterogenous group, with much confusion about nature and classification of these neoplasms in the past. Diagnosis is based primarily on light microscopy and confirmed by immunohistochemistry and electron microscopy. A classification in 4 different types; paraganglioma, typical carcinoid, atypical carcinoid and small cell neuroendocrine carcinoma (SCNC) is a current consensus. Thorough diagnostic and a proper classification of neuroendocrine neoplasms are of paramount importance--prognosis and treatment differ significantly. We present two cases: 63-year old patient with SCNC of the larynx and a 53-year old patient with atypical carcinoid of the larynx. OctreoScan is useful tools for diagnostics and follow up of the patients and it is predictive for effectiveness of octreotide therapy.
