Ultrasound Contrast Marking And Papillary Thyroid Cancer Genetics

Objective1. To collect the whole genomic CNA data of Chinese sporadic PTCs, and gather the common chromosomal imbalances with their covered candidate gene groups.2. To select the core functional genes correlated with the pathogenesis and biological phenotype of Chinese sporadic PTC with meta-analysis.Materials and methods39patients were included in this study, total thyroidectomy were taken in PUMCH with clinically and pathologically confirmed sporadic PTC. The mean ages of the39PTCs was40.00±13.82years, with8cases of male and33cases of female. PCR sequencing of BRAF(V600E) and RAS mutation, immune-histochemical examination(IHC) of RET expression were performed. array-CGH was carried out in33of the39PTCs, and the common CNAs of33sporadic PTCs were selected by DNA analytics system from Angilent. Meta-analysis was performed for gene functional grouping and mapping of the pathway network. CNA of the33PTCs in this study was grouped into3types:PTC with normal CNA (N-CNA), PTC with low-variance CNAs (L-CNAs) and PTC with significant abnormal CNAs (A-CNAs), the clinical and biological phenotypes between the3groups were compared. Distinct CNAs with the covered candidate gene groups in the3different CNA types were selected and analyzed by meta-analysis, the difference of the gene type and their function in the pathway networks were compared.Results1. Low variability of chromosomal imbalance is a feature of the33sporadic PTCs;2. The incidence of BRAF(V600E) was (58.97%) in all the39PTCs,5PTCs with RET expression in IHC, the combined incidence of BRAF mutation and RET was71.79%, and no correlation was found between the lymphanode metastasis and the BRAF/RET mutation. No RAS mutation was detected in39PTCs. 3. The incidence of BRAF/RET mutation was higher in N-CNA and A-CNAs groups, comparing with the L-CNAs group. Significant difference was detected between the A-CNAs and L/N-CNAs groups in some clinical features, such as the tumor size and age of the patients.4. Meta-analysis results of the common CNAs in33sporadic PTCs showed that the pathogenesis of sporadic PTC involved several pathways besides classical MAPK pathway; meta-analysis results discovered differences in functional gene groups and related pathway networks between the A-CNAs and L-CNAs group.Conclusion1. Significant copy number variation is not the main genetic event in Chinese sporadic PTCs.2. BRAF (V600E) is the most frequent MAPK pathway related gene mutation in this study group, which might play a key role in the pathogenesis among the N-CNA PTC group. A-CNAs seemed to conceive a more complicated pathogenesis, which might be regulated by several pathways besides the classical MAPK pathway activation. The pathogenesis of L-CNAs is correlated more closely to the functional gene groups in CNAs. Objective1. To evaluate the contrast enhanced perfusion pattern of PTC micro-vascular imaging (MVI) quantitatively.2. To investigate the correlation between PTC MVI features and CD34micro-vascular density (MVD), vascular endothelial growth factor (VEGF), BRAF (V600E) mutation,3. To discuss the correlation of PTC MVI pattern and CNA, together with the candidate gene groups.Method and materials39pathological and clinical confirmed sporadic PTCs were evaluated with real-time gray-scale contrast-enhanced micro-vascular imaging under a low mechanical index. The micro-bubble agent was SoneVue. Of the39PTCs,33were classical PTCs,6were PTC with follicular variant (FVPTC). The AROI,which is the subtraction of peak echo intensity between the lesion region of interest (ROI) and normal thyroid parenchyma ROI, was used to evaluate the perfusion characteristics of PTC MVI quantitatively. The paraffined specimens were selected for immunohistochemical (IHC) staining for CD34and VEGF, and the correlation between△ROI and the CD34, VEGF expression level, the BRAF mutation and CNA groups were evaluated.Results1.△ROI was strongly correlated with the CD34expression(p=0.000), significant differences were detected in the distribution pattern of AROI value among different CD34expression levels, no overlapping of the mean△ROI values and the95%confidence intervals was found among the3CD34expression levels.2. The PTC MVI perfusion was classified into3patterns, low perfusion, focal perfusion and high perfusion, on the basis of combining△ROI values with the peak ehco pattern in time-intensity curve. 3. The median and high VEGF expression level was the mainstay in BRAF (+) PTC. Multi-variance logistic regression analysis showed that VEGF expression level was the independent factor for BRAF mutation.4. The A-CNA PTCs presented mainly with high and focal perfusion pattern, the L-CNA PTCs showed a combination of focal and low perfusion, the N-CNA PTCs mostly demonstrated low perfusion patterns. The mean AROI values rose with the extent of CNAs.Conclusions1. AROI is an objective indicator for the evaluation of PTC MVI pattern and intensity.2. VEGF expression level is the independent effect factor for the BRAF (600E) mutation, the over expression of VEGF might play a key role in the regulation of MAPK pathway activation and other pathways potentially related to the pathogenesis of PTC.3. The MVI perfusion intensity of PTC rose with the extent of CNAs, which showed a positive correlation.