RESUMO
OBJECTIVE: Treatment of acute lymphoblastic leukemia (ALL) in adults focuses on the initial assessment of the prognostic relevant cytogenetic features as well as a response-guided therapy based on molecular data. We examined the importance of molecular-cytogenetic abnormalities for complete remission (CR) rates and the overall survival (OS) in adult ALLs. METHODS: Conventional cytogenetics and fluorescence in situ hybridization were performed on bone marrow cells from 33 newly-diagnosed ALL adults. Two karyotype categories [standard- risk group- normal karyotype, hyperdiplody and other structural aberrations, and high-risk group-t(11q23)/MLL, t(9;22)/bcr-abl, t(1;19), t(8;14), C-MYC and complex karyotype] and the biologically and clinically relevant ALL ploidy subgroups were prospectively defined. RESULTS: Chromosomal abnormalities were found in 52% of the cases with a high rate of poor-risk translocations - t(9;22), t(8q24), t(11q23), t(1;19). The total CR rate was 67% and the median time for achievement 2.33 months. Male sex, an age below 35 years and the absence of high risk translocations might have contributed to the high CR rates. Female patients, hyperdiplody, low white blood cells (WBC), and random cytogenetic aberrations had the longest OS. OS, 3- and 5-years survival periods were significantly shorter for poor-risk than standard risk group (p=.015, p=.001 and p=.005, respectively). CONCLUSION: This study emphasizes the lack of influence of cytogenetic aberrations on the CR and the time to achieve CR. However, our observations show that these aberrations are an independent prognostic factor in adult ALL - they allow predicting therapy resistance and the OS time after intense treatment.
RESUMO
OBJECTIVE: The objective of this study was to assess the implication of copy number changes of epidermal growth factor receptor (EGFR) in lung cancer pathogenesis. MATERIALS AND METHODS: We used the highly reliable method of FISH, applied on tissue microarray (TMA), containing 306 lung tumors of different histological types, grades and tumor stage, in order to analyze the correlations between gene copy number changes and tumor phenotype. RESULTS: The frequency of EGFR copy number changes was 22.2%-2.8% amplifications and 19.4% gains. EGFR gains occurred more commonly in the squamous cell cancers (23.5%) than in adenocarcinomas (11.8%). Amplifications of EGFR were found only in the squamous cell cancers. Regarding cancer phenotype, there was a statistically significant correlation between EGFR copy number changes and histological grade (p = 0.001). No statistically significant relation could be observed with the metastatic spread of the tumors (lymphogenic and haematogenic) (p = 0.082 and p = 0.1, respectively). In our study EGFR could not be determined as a prognostic factor of survival (p = 0.6115). CONCLUSION: EGFR copy number changes could supplement the clinical significance of EGFR as a marker related to its pathogenesis and targeted therapy.