ABSTRACT
Tumors of the head and neck, more specifically the squamous cell carcinoma, often show upregulation of the Hedgehog signaling pathway. However, almost nothing is known about its role in the sinonasal adenocarcinoma, either in intestinal or non-intestinal subtypes. In this work, we have analyzed immunohistochemical staining of six Hedgehog pathway proteins, sonic Hedgehog (SHH), Indian Hedgehog (IHH), Patched1 (PTCH1), Gli family zinc finger 1 (GLI1), Gli family zinc finger 2 (GLI2), and Gli family zinc finger 3 (GLI3), on 21 samples of sinonasal adenocarcinoma and compared them with six colon adenocarcinoma and three salivary gland tumors, as well as with matching healthy tissue, where available. We have detected GLI2 and PTCH1 in the majority of samples and also GLI1 in a subset of samples, while GLI3 and the ligands SHH and IHH were generally not detected. PTCH1 pattern of staining shows an interesting pattern, where healthy samples are mostly positive in the stromal compartment, while the signal shifts to the tumor compartment in tumors. This, taken together with a stronger signal of GLI2 in tumors compared to non-tumor tissues, suggests that the Hedgehog pathway is indeed activated in sinonasal adenocarcinoma. As Hedgehog pathway inhibitors are being tested in combination with other therapies for head and neck squamous cell carcinoma, this could provide a therapeutic option for patients with sinonasal adenocarcinoma as well.
Subject(s)
Adenocarcinoma , Hedgehog Proteins , Immunohistochemistry , Signal Transduction , Zinc Finger Protein Gli2 , Humans , Hedgehog Proteins/metabolism , Hedgehog Proteins/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Male , Female , Zinc Finger Protein Gli2/metabolism , Zinc Finger Protein Gli2/genetics , Middle Aged , Pilot Projects , Aged , Patched-1 Receptor/metabolism , Patched-1 Receptor/genetics , Zinc Finger Protein GLI1/metabolism , Zinc Finger Protein GLI1/genetics , Zinc Finger Protein Gli3/metabolism , Zinc Finger Protein Gli3/genetics , Paranasal Sinus Neoplasms/metabolism , Paranasal Sinus Neoplasms/pathology , Adult , Gene Expression Regulation, Neoplastic , Nerve Tissue Proteins , Nuclear ProteinsABSTRACT
Oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) are the most common types of cancers in the head and neck region (HNSCC). Despite very aggressive treatment modalities, the five-year survival rate has not changed for decades and is still around 60%. The search for potential specific biomarkers of aggressiveness or outcome indicators could be of great benefit in improving the treatment of these patients. One of the potential biomarkers is survivin, the protein product of the BIRC5 gene. In this study, we investigated the occurrence of BIRC5 gene polymorphisms in 48 patients with OSCC and OPSCC compared with healthy controls. A total of 18 polymorphisms were found, 11 of which occurred in HNSCC with a minor allele frequency (MAF) of more than 5%. Five polymorphisms (rs3764383, rs9904341, rs2071214, rs2239680, rs2661694) were significantly associated with tumor size, tumor stage, and advanced regional disease, but had no impact on survival.
