Imaging And Molecular Features Of Intrahepatic Mass-forming Cholangiocarcinomas And Molecular Features Of Endometrial Cancer

Part 1. Imaging features of intrahepatic mass-forming cholangiocarcinomas on Gd-BOPTA-enhanced MRIObjectives: The aims of this study are to describe the imaging features of intrahepatic mass-forming cholangiogcarcinoma (IMC) and to evaluate the patterns and degree of enhancement of IMC with emphasis on the delayed phase and hepatobiliary phase(HBP) on Gd-BOPTA-enhanced MR imaging.Methods: We retrospectively reviewed 36 patients with pathologically proven IMCs who underwent liver MR using a 3.0 T scanner with the hepatocyte-specific contrast agent gadobenate dimeglumine (Gd-BOPOTA) between March 2011 and June 2015.We observed the following MR images: unenhanced T1WI, T2WI, DWI, dynamic phases (including the arterial phase, portal venous phase, and 10min delayed phase)and 90min HBP. We evaluated the signal intensity, enhancement pattern, degree of enhancement and conspicuity of each IMC qualitatively and quantitatively. We also analyzed diffusion-weighted (DW) images and measured the apparent diffusion coefficient (ADC) values of each lesion. The statistical significance of these findings were determined with Wilcoxon signed-rank test and two-tailed unpaired Student' s t test.Results: We evaluated 66 lesions in 66 patients. In the dynamic phase images, 57 lesions(86.4%) exhibited peripheral rim-like enhancement in the arterial phase followed by progressive centripetal enhancement in the portal venous and delayed phases. In the 10min delayed phase images, all lesions(100%) exhibited peripheral rim-like hypointensity with central inhomogeneous hyperintensity or hypointensity.On HBP, 61 lesions(92.4%) exhibited peripheral rim-like hypointensity with central hyperintensity. Additionally, 57 lesions(86.4%) exhibited peripheral hyperintensity with central inhomogeneous hypointensity or mixed signals on diffusion-weighted(DW) images. In the HBP images, the IMCs exhibited the highest conspicuities(median, 5; interquartile range, 4-5). On the HBP images, the degrees of enhancement were higher in the moderately differentiated tumors (48.2%±15.6%) than in the poorly differentiated tumors (35.5%±18.9%) and in the lesions without lymph node metastasis (47.6%±18.8%) than in the lesions with lymph node metastasis (33.7%±19.6%). Additionally, the ADC values of the poorly differentiated tumors (0.75×10-3 mm2/s±0.18×10-3 mm2/s) were lower than those of the moderately differentiated tumors (0.98×10-3 mm2/s± 0.22 ×10-3 mm2/s).Conclusions: The most prevalent enhancement pattern of the IMCs on the Gd-BOPTA-enhanced images was peripheral rim enhancement in the arterial phase and gradual enhancement in the portal venous and delayed phases. The typical pattern of the IMCs on the HBP images was peripheral hypointensity with central hyperintensity, which differed from the performances on the HBP images in the Gd-EOB-DTPA-enhanced imaging. The “target appearance” was exhibited in the delayed phase and HBP images with the characteristics of peripheral rim-like IMC hypointensity. Similarly, this target appearance was also observed on the DW images,which exhibited peripheral rim-like hyperintensity. Additionally, the IMCs exhibited higher conspicuity and better delineation on the HBP images, and the ADC values of poorly differentiated IMCs were lower than those of the moderately differentiated tumors, which may aid reasonable surgical planning and improve prognoses.Part2.Correlations between ADC values and molecular marker of Ki-67 in intrahepatic mass-forming cholangiocarcinomas in 3.0T MRAim: Cholangiocarcinoma is the second-most common primary tumor of the liver.Ki-67 is a tumor proliferation marker.The purpose of the study was to evaluate the apparent diffusion coefficient (ADC) value and the molecular markers Ki-67 in intrahepatic mass-forming cholangiocarcinoma.Materials and methods: We retrospectively analyzed 9 moderately differentiated cholangiocarcinomas with low Ki-67 labeling index (LI), 7 moderately differentiated cholangiocarcinomas with a high Ki-67 LI and 22 poorly differentiated cholangiocarcinomas,all the patients underwent magnetic resonance(MR)examination including diffusion-weighted(DW)imaging.The mean ADC value of cholangiocarcinoma was calculated from two layers of DW images (b=0,800sec/mm2). Immunohistochemical Ki-67 staining was assessed to determine the cholangiocarcinoma Ki-67 LI.Results: The mean ADC value of intrahepatic mass-forming cholangiocarcinoma was negatively correlated with Ki-67 LI (r=-0.699, P=0.000). An inverse association between the mean ADC and Ki-67 LI value were also evaluated in moderately differentiated cholangiocarcinomas (r=-0.633, P=0.025) and in poorly differentiated cholangiocarcinomas (r=-0.589, P=0.037). The mean ADC values of moderately differentiated cholangiocarcinoma with high Ki-67 LIs and with low Ki-67 LIs were(0.78×10-3 mm2/s±0.15×10-3 mm2/s)and (1.21×10-3 mm2/s±0.22 ×10-3 mm2/s),respectively. The former ADC value was significantly lower than the latter ADC value(P=0.007). There were not significant difference between the mean ADC values ofmoderately differentiated cholangiocarcinomas with high Ki-67 LIs (0.78×10-3 mm2/s±0.15×10-3 mm2/s) and poorly differentiated cholangiocarcinomas (0.79X 1 0-3 mm2/s ± 0.12×10-3 mm2/s).(P=0.621).Conclusion: Our study indicate that the ADC value can reflect the proliferative activity of tumor and can also predict the differentiation of intrahepatic mass-forming cholangiocarcinoma.Part 3.Expression profile of long non-coding RNAs in endometrial cancerObjectives: This study was to uncover the role of long non-coding RNA (lncRNA) in the process of endometrial cancer (EC) development using microarray technique to obtain the expression profiles of IncRNAs in EC and its adjacent normal tissues.Methods: A total of 45 pieces of pathologically-proven EC tissues were used in this study. All samples were frozen in liquid nitrogen immediately after resection and stored at -80? for future use. The detection of lncRNA and transcripts was conducted using microarray analysis. To understand the biochemical function of IncRNA,bioinformatics analyses (gene ontology and pathway analyses) were performed. To further investigate the relationship between lncRNAs and EC, subgroup analysis was conducted. In order to validate the consistency of the lncRNAs with microarray data,qRT-PCR was performed.Results: In this study, 30586 IncRNAs and 26109 mRNA (fold change >2.0) were found in the tested EC. In particular, compared with normal tissues, 4010 the IncRNA were up-regulated, and 3350 of them were down-regulated. Seven of the lncRNAs were in accordance with microarray data in qRT-PCR. Among these IncRNAs, 3 were up-regulated and 4 were down-regulated. Furthermore, pathway analysis revealed that 24 pathways were correlated to the up-regulated transcripts, while 27 pathways were associated with the down-regulated transcripts.Conclusions: Our study demonstrated that the expressions of a large amount of IncRNAs were altered in EC in comparison to normal tissues, suggesting that lncRNAs could potentially serve as a diagnostic biomarker that is beneficial for the diagnosis and therapy of EC.