ABSTRACT
BACKGROUND: Methylation of tumor suppressor genes has been investigated in all kinds of cancer. Tumor specific epigenetic alterations can be used as a molecular markers of malignancy, which can lead to better diagnosis, prognosis and therapy. Therefore, the aim of this study was to evaluate the association between gene hypermethylation and expression of fragile histidine triad (FHIT), glutathione S-transferase P1 (GSTP1) and p16 genes and various clinicopathologic characteristics in primary non-small cell lung carcinomas (NSCLC). MATERIALS AND METHODS: The study included 28 primary non-small cell lung carcinomas, where an additional 28 tissue samples taken from apparently normal safety margin surrounding the tumors served as controls. Methylation-specific polymerase chain reaction (MSP) was performed to analyze the methylation status of FHIT, GSTP1 and p16 while their mRNA expression levels were measured using a real-time PCR assay with SYBR Green I. RESULTS: The methylation frequencies of the genes tested in NSCLC specimens were 53.6% for FHIT, 25% for GSTP1, and 0% for p16, and the risk of FHIT hypermethylation increased among patients with NSCLC by 2.88, while the risk of GSTP1 hypermethylation increased by 2.33. Hypermethylation of FHIT gene showed a highly significant correlation with pathologic stage (p<0.01) and a significant correlation with smoking habit and FHIT mRNA expression level (p<0.05). In contrast, no correlation was observed between the methylation of GSTP1 or p16 and smoking habit or any other parameter investigated (p>0.05). CONCLUSIONS: RESULTS of the present study suggest that methylation of FHIT is a useful biomarker of biologically aggressive disease in patients with NSCLC. FHIT methylation may play a role in lung cancer later metastatic stages while GSTP1 methylation may rather play a role in the early pathogenesis.
Subject(s)
Acid Anhydride Hydrolases/biosynthesis , Cyclin-Dependent Kinase Inhibitor p16/biosynthesis , DNA Methylation/genetics , Glutathione S-Transferase pi/biosynthesis , Lung Neoplasms/genetics , Neoplasm Proteins/biosynthesis , Acid Anhydride Hydrolases/genetics , Adult , Aged , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Cyclin-Dependent Kinase Inhibitor p16/genetics , Egypt , Female , Glutathione S-Transferase pi/genetics , Humans , Male , Middle Aged , Neoplasm Proteins/genetics , Prognosis , Promoter Regions, Genetic/genetics , RNA, Messenger/biosynthesis , SmokingABSTRACT
BACKGROUND: Superior sulcus tumors are a complex subset of tumors accounting for less than 5% of lung tumors. METHODS: Twenty-three patients admitted between 2001 and 2007 were included in the study,. Computed tomography scan of the chest was considered the primary diagnostic and staging investigation for all patients. Radiation therapy was given preoperatively to 20 patients, neoadjuvant chemotherapy was given to 13 patients. RESULTS: There were 22 men and one woman in the study. The mean age was 53 years. Lobectomy was performed in 20 patients and wedge resection was done for three patients. Three to five ribs were resected in all patients. Extended resections were performed in eight patients. Positive mediastinal lymph nodes were found six patients. The staging was: Stage IIB (11 patients); Stage IIIA (four patients), Stage IIIB (six patients) and Stage IV (two patients). Negative resection margin was achieved in 18 patients. Postoperative complications developed in nine patients, there was one operation related mortality. Tumor recurrence developed in 16 patients. The mean survival time was 2.8 years and the overall 5-years survival was 26%. CONCLUSION: Multimodality treatment gives satisfactory results with low morbidity and mortality rates and acceptable survival.
