甲状腺癌的概念和诊疗.pptVIP

* * 13 patients -- 8WT, 5 BRAF V600E Statistically significant chi-squared p 0.02 WT PFS reached @ 54 weeks V600E PFS not reached * We reported data on 13 patients that showed improved PFS in pts with BRAF V600E In our expanded analysis to 22 pts with DTC, the effect is no longer significant but the trend exists. We are further investigating BRAF copy number in these patients- we think that this is reason that we no longer see the effect _ (I.e. some of WT BRAF patients are actually overexpressing the BRAF protein and are thus like the mutants.-- more on this later- WHAT’s important is that all of the RAS genes were wild-type -- so it does not seem that an underlying mutation in RAS is the underlying molecular mechanism for the improved PFS seen in FTC-- so what is this mechanism * * * However Our BRAF data is important given in a retrospective analysis of patients from the pre-kinase era, BRAFV600E patients have done worse. Traditionally BAF V600E correlated with a worse survival and poorer outcome in WDTC This directly contradicts our recent findings * As we showed before, upon further analysis the difference between BRAF WT V600E has lost statistical significance as we have increased our number of specimens. It is possible that this is due to chance, and that with the completion of all 50+ specimens the statistical significance will return. However another possibility is copy number gain, especially in FTC, may account for this difference. This was first shown in 2005 by Ciampi et al. They looked at 62 FTC, 32 PTC -- they found that although rare in PTC, copy number gain is quite common in FTC/ Hurthle cell neoplasms. (16-45%) Copy number gain involves either amplification of the BRAF gene or increased number of copies of chromosome 7. Shown above is a slide if FISH (fluorescence in situ hybridization) with a BRAF specific and Chromosome 7 specific probe. There data has shown that FTC with copy number gain is more widely invasive, thus demonstratin