ABSTRACT
Extensive molecular studies in development of the squamous cell carcinoma of larynx (SCCL) indicated the involvement of a variety of genes including the MLH1. To search for possible mechanism leading to MLH1 silencing in SCCL we studied LOH and promoter methylation in a homogeneous set of 62 larynx cancers. Then we evaluated immunohistochemically the MLH1 expression for 51 tumor specimens. Further, the results were correlated with microsatellite instability and subsequently with the clinical course of the disease. LOH at the MLH1 locus and aberrant methylation of its promoter were found in 47.9 and in 22.6% of tumors, respectively. A decreased expression was observed in 27.5% of the cases. MSI analysis of tumor DNA showed a microsatellite stable phenotype in 59 cases (95.2%). From our study it can be concluded that: i) molecular alterations of MLH1 play an important role in SSCL development, ii) both LOH and aberrant methylation contribute to the MLH1 inactivation in SCCL and are associated with a less advanced stage of differentiation of larynx tumors, iii) MLH1 inactivation does not lead to MSI in larynx cancer and MSI may not contribute to the development of SCCL.
Subject(s)
DNA Methylation , Neoplasm Proteins/genetics , Promoter Regions, Genetic , Adaptor Proteins, Signal Transducing , Carrier Proteins , Cell Line, Tumor , Gene Silencing , Humans , Immunohistochemistry , Laryngeal Neoplasms/genetics , Loss of Heterozygosity , Microsatellite Repeats , MutL Protein Homolog 1 , Nuclear ProteinsABSTRACT
Gastroesophageal reflux disease (GERD) is considered an important etiological factor of numerous larynx dysfunctions. The goal of our study was to describe larynx status of patients with GERD before and after treatment. Forty-five patients with GERD symptoms entered our study. GERD was confirmed in 24-hours pH-metric examination. Patients were treated with proton pump inhibitors in doses chosen accordingly to GERD severity. All patients underwent endoscopic evaluation of the larynx and acoustic voice analysis before and after the treatment. GERD was diagnosed in 35 out of 45 patients. Acoustic voice analysis revealed that voice disorders appeared more often in patients with severe than moderate or mild refluxes (p = 0.023). Laryngeal changes found in endoscopic evaluation also depended on reflux severity (p = 0.05). The voice quality improved (p = 0.031) and the changes in larynx diminished after anti-reflux treatment (p = 0.016).
