elafin and Head-and-Neck-Neoplasms

Topics: Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Elafin; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Viral; Head and Neck Neoplasms; Human papillomavirus 16; Humans; Mice; Molecular Targeted Therapy; Oncogene Proteins, Viral; Papillomavirus E7 Proteins; Papillomavirus Infections; Receptor, ErbB-3; Repressor Proteins; RNA, Small Interfering; Squamous Cell Carcinoma of Head and Neck; Xenograft Model Antitumor Assays

Two studies published in this issue of Cancer Discovery describe the emerging mutational landscape of head and neck squamous cell carcinomas (HNSCC) and their genomic and epigenetic alterations, thus identifying novel actionable cancer drivers and predictive biomarkers for targeted therapies. Most genomic alterations in HNSCC converge in a handful of molecular pathways, resulting in cell-cycle deregulation, genomic instability, cell differentiation defects, and persistent mitogenic signaling, the latter involving aberrant phosphoinositide 3-kinase (PI3K)/mTOR pathway activation, thereby rendering HNSCC responsive to PI3K/mTOR inhibitors. Cancer Discov; 3(7); 722-5. ©2013 AACR.

Topics: Carcinoma, Squamous Cell; Cell Cycle; Elafin; Gene Expression Regulation, Neoplastic; Genomic Instability; Head and Neck Neoplasms; Humans; Molecular Targeted Therapy; Protein Kinase Inhibitors; Signal Transduction; TOR Serine-Threonine Kinases

The etiology of inflammatory myofibroblastic tumors (IMTs) is controversial and the prognosis is unpredictable. Previous studies have not investigated the expression of hypoxia-related markers in IMTs.. Between 2002 and 2012, 12 consecutive patients with histologically proven IMTs were enrolled in the study. Immunohistochemistry was used to detect GLUT-1, HIF-1α, PI3K, and p-Akt expression in paraffin-embedded tumor specimens. Associations among GLUT-1, HIF-1α, PI3K, and p-Akt protein expression and clinical parameters were investigated.. The mean duration of follow-up was 52.1 months (range, 11 to 132 months). Six patients had local recurrence. GLUT-1, HIF-1α, PI3K, and p-Akt expression were detected in 41.7%, 50.0%, 33.3%, and 41.7% of patients, respectively. Fisher's exact test revealed significant correlations between recurrence of IMT and PI3K expression (P = 0.01) and p-Akt expression (P = 0.015). Univariate analyses revealed significant correlations between survival and GLUT-1 expression (P = 0.028), PI3K expression (P = 0.006), and p-Akt expression (P = 0.028). Multivariate analysis did not show a significant relationship between survival and GLUT-1, HIF-1α, PI3K, or p-Akt. Spearman rank correlation analysis showed significant correlations between HIF-1α and PI3K expression (r = 0.707, P = 0.01) and between p-Akt and PI3K expression (r = 0.837, P = 0.001).. Although our results are inconclusive owing to the small sample size, they suggest that PI3K and p-Akt expression may play a role in the recurrence of IMTs of the head and neck.

Topics: Adult; Biomarkers, Tumor; Elafin; Female; Follow-Up Studies; Glucose Transporter Type 1; Head and Neck Neoplasms; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Immunoenzyme Techniques; Inflammation; Lymphatic Metastasis; Male; Middle Aged; Myofibroblasts; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasms, Muscle Tissue; Phosphatidylinositol 3-Kinases; Prognosis; Proto-Oncogene Proteins c-akt; Young Adult