Up-regulation of AKAP13 and MAGT1 on cytoplasmic membrane in progressive hepatocellular carcinoma: a novel target for prognosis

Hepatocellular carcinoma (HCC) is one of the most common cancers and is associated with high mortality worldwide. The current gold standards for HCC surveillance are detection of serum α-fetoprotein (AFP) and ultrasonography; however, non-specificity of AFP and ultrasonography has frequently been reported. Therefore, alternative tools, especially novel specific tumor markers, are required. In this study, cytoplasmic membrane proteins were isolated from phorbol 12-myristate 13-acetate (PMA)-induced invasive HepG2 cells and identified using nano-scale liquid chromatographic tandem mass spectrometry (NLC-MS/MS) with comparison to non-treated controls. The results showed that two proteins, magnesium transporter protein 1 (MAGT1) and A-kinase anchor protein 13 (AKAP13), were highly expressed in PMA-treated HepG2 cells. This up-regulation was confirmed by real-time RT-PCR, western blot analysis, and immunofluorescent staining studies. Furthermore, evaluation of MAGT1 and AKAP13 expression in clinical HCC tissues by immunohistochemistry suggested that both proteins were strongly expressed in tumor tissues with significantly higher average immunoreactive scores of Remmele and Stegner (IRS) than in non-tumor tissues (P ≤ 0.005). In conclusion, the expression levels of MAGT1 and AKAP13 in HCC may be potential biomarkers for the diagnosis and prognosis of this cancer.     

Premalignant lesions of cholangiocarcinoma: characteristics on ultrasonography and MRI

Background and objective

Cholangiocarcinoma (CCA) is an aggressive malignancy with high prevalence rate in Asia. The CCA premalignant lesions, including Biliary intraepithelial neoplasia (Bil-IN) and Intraductal papillary neoplasm of biliary tract (IPNB), share a common carcinogenesis; however, on imaging, patterns of presentation are different. Patterns and imaging characteristics on ultrasonography (US) and Magnetic resonance imaging (MRI) of both Bil-IN and IPNB are reported herein.

Methods

In this retrospective study of imaging findings in premalignant CCA, pathology-proven cases of Bil-IN and IPNB at Chulabhorn Hospital were analyzed. Demographics, locations of lesions, imaging characteristics of both Bil-IN and IPNB were assessed, compared, and described.

Results

Twenty-one premalignant lesions, 13 Bil-INs and 8 IPNBs, from 18 patients were included. Both Bil-IN and IPNB lesions were found more commonly at the right than left intrahepatic ducts (66.7% vs. 33.3%), and had more peripheral than central locations (85.7% vs. 14.3%). On US, Bil-IN commonly presented as focal bile duct dilatation (76.9%), whereas IPNB was more variable with hyperechoic nodules (37.5%), focal bile duct dilatation (37.5%), and diffuse bile duct dilatation with intraductal nodules (25%). On MRI, focal bile duct dilatation and nonfunctioning bile excretion are the most sensitive findings with sensitivities in the range of 84.6% to 100%. The presence of intraductal nodules and connection to the biliary system are findings that were significantly different between IPNB and Bil-IN, 62.5% versus 7.7% (p = 0.014) and 75% versus 15.4% (p = 0.018), respectively.

Conclusions

Premalignant lesions of CCA, including Bil-IN and IPNB, have different imaging presentations. Knowledge of imaging presentations may improve early detection and increase confidence in diagnosis.