Gadoxetic acid–enhanced MRI had high interobserver variability and low diagnostic performance in the detection of microvascular invasion of hepatocellular carcinoma; therefore, caution is required ... Background Accurate identification of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) before treatment is critical for selecting a proper treatment strategy. Purpose To evaluate the ...

Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC), microsatellite instability (MSI), and tumor mutation burden (TMB) have been proposed as a predictive biomarker to predict response to immune checkpoint blockade (ICB). We aimed to find the relationship of PD-L1 IHC to TMB and MSI using a comprehensive cancer panel assay (CCPA) with >500 genes in advanced cancer patients. CCPA results from 588 archived tissue samples were analyzed for TMB and MSI. In seven samples, whole exome sequencing confirmed TMB with Pearson’s correlation coefficient of 0.972 and all MSI-high cases were validated by pentaplex PCR. Association of TMB and MSI with their corresponding PD-L1 IHC was analyzed. The median TMB value of 588 cases was 8.25 mutations (mut)/Mb (range 0–426.8) with different distributions among the tumor types, with high proportions of high-TMB (>10mut/Mb) in tumors from melanoma, colorectal, gastric, and biliary tract. The TMB values significantly correlated with PD-L1 expression, and this correlation was prominent in gastric and biliary tract cancers. Moreover, the MSI score, the proportion of unstable MSI sites to total assessed MSI sites, showed a significant correlation with the TMB values and PD-L1 scores. This study demonstrates that PD-L1 expression is significantly associated with TMB and MSI score and this correlation depends on the location of the primary tumor.

Hepatocellular carcinoma (HCC) has one of the highest mortality rates among solid cancers. Late diagnosis and a lack of efficacious treatment options contribute to the dismal prognosis of HCC. Immune checkpoint inhibitor (ICI)-based immunotherapy has presented a new milestone in the treatment of cancer. Immunotherapy has yielded remarkable treatment responses in a range of cancer types including HCC. Based on the therapeutic effect of ICI alone (programmed cell death (PD)-1/programmed death-ligand1 (PD-L)1 antibody), investigators have developed combined ICI therapies including ICI + ICI, ICI + tyrosine kinase inhibitor (TKI), and ICI + locoregional treatment or novel immunotherapy. Although these regimens have demonstrated increasing treatment efficacy with the addition of novel drugs, the development of biomarkers to predict toxicity and treatment response in patients receiving ICI is in urgent need. PD-L1 expression in tumor cells received the most attention in early studies among various predictive biomarkers. However, PD-L1 expression alone has limited utility as a predictive biomarker in HCC. Accordingly, subsequent studies have evaluated the utility of tumor mutational burden (TMB), gene signatures, and multiplex immunohistochemistry (IHC) as predictive biomarkers. In this review, we aim to discuss the current state of immunotherapy for HCC, the results of the predictive biomarker studies, and future direction.

Recently, the 8th edition staging system of the American Joint Committee on Cancer (AJCC) for hepatocellular carcinoma (HCC) was released, including a change in T category. We aimed to validate the new AJCC system. The predictive value of the new AJCC was validated in comparison to the previous edition, in a total 1,008 patients who underwent curative resection for HCC as initial treatment. The 2-year area under the curve values for recurrence-free survival (RFS) and overall survival (OS) were comparable in the 7th and 8th editions. Stage migration was observed in 63 patients (6.3%); from T2 to T1a for 44 patients and from T3 to T4 for 19 patients. The RFS and OS were not different between T1a and T1b in the 8th edition. For solitary tumors ≤ 2 cm, those with microvascular invasion had lower RFS and OS values than those without although they were all classified as T1a in the 8th edition. Tumors involving a major branch of the portal or hepatic vein (T4 by the 8th edition and T3b by the 7th edition) had shorter RFS and OS than multifocal tumors, at least one of which was > 5 cm (T3 by the 8th edition and T3a by the 7th edition). The AJCC 8th edition staging system for HCC showed comparable predictive performance to the 7th edition. It is desirable in a future revision to consider sub-stratification of solitary tumors ≤ 2 cm (T1a) depending on the presence of vascular invasion, which is not included in the 8th edition.

Background/Aim: Pregnancy up-regulated non-ubiquitous calmodulin kinase (PNCK) is a member of calmodulin kinase, and overexpression of PNCK with involvement in carcinogenesis have been reported in HER-2 amplified breast cancer, clear cell renal cell carcinoma and nasopharygeal carcinoma. However, the expression of PNCK and its clinical implication have not been elucidated in hepatocellular carcinoma (HCC). Materials and Methods: We investigated PNCK expression at both the protein and mRNA level using immunohistochemistry (IHC) and microarray gene expression profiling in HCC tissue samples, and evaluated its association with clinicopathological parameters and their potential prognostic significance. Results: High PNCK protein expression and high PNCK mRNA level was observed in 61.7% and 34.7% of total HCC cases, respectively. PNCK mRNA level was higher in tumor tissues than in background non-tumor tissues, and significantly correlated with protein expression by IHC. High PNCK expression was associated with higher Edmondson grade, intrahepatic metastasis, microvascular invasion and higher AFP levels. Patients with high PNCK expression showed shorter recurrence-free survival and disease-specific survival, and high mRNA expression of PNCK was an independent prognostic factor in disease-specific survival. Conclusion: Up-regulation of PNCK expression as well as its association with poor prognosis was demonstrated in HCC. PNCK might be a prognostic biomarker of HCC, and could be a potential candidate therapeutic target.