The role of pathology and pathologists in the detection and management of cancer

published_or_final_versio

Focal fatty change: a rare hepatic manifestation of diabetes mellitus

Focal fatty change of the liver is a rare and poorly recognised entity. Most of the previously reported cases occurred in patients suffering from the usual steatogenic conditions, such as diabetes mellitus and obesity. The focality of the lesion, however, remains unexplained. The author reports a rare case of subcapsular focal fatty change of the liver occurring in a 60-year-old Chinese woman suffering from poorly controlled adult-onset diabetes mellitus. The underlying pathogenesis for the focal fatty change is thought to be related to local ischaemic effect secondary to diabetic angiopathy, which may further enhance the steatogenicity of diabetes mellitus. The recognition of focal fatty change of the liver is important in order to avoid misdiagnosis of other space-occupying lesions radiologically and macroscopically.published_or_final_versio

Langerhans' cell histiocytosis: Possible association with malignant germ cell tumour

A rare case of adult onset Langerhans' cell histiocytosis associated with dysgerminoma in a 35 year old Chinese woman is reported. The patient had a history of dysgerminoma of left ovary 15 years previously and had undergone surgery followed by radiotherapy and an uneventful recovery. She presented again in March 1994, this time with a left clavicular mass, which was shown histologically to be Langerhans' cell histiocytosis. The report illustrates the probable association between the two lesions, with some discussion on the underlying pathogenesis.published_or_final_versio

Gender disparity of hepatocellular carcinoma: role of hepatitis B virus X protein and androgen receptor

Key Messages 1. The natural COOH-terminal truncated HBx was more frequently detected in hepatocellular carcinoma (HCC) in male than female patients. 2. There was no significant clinicopathological correlation with the HBx status or remarkable changes in androgen receptor (AR) expression in the presence of different truncated HBx mutants compared with full-length HBx. 3. Lower expression of AR was associated with more aggressive tumour phenotype and a higher metastatic potential of HCC.published_or_final_versio

Hepatic progenitor cells: their role and functional significance in the new classification of primary liver cancers

Hepatic progenitor cells (HPCs) are bipotential cells residing in normal liver. Their proliferation is observed in reactive conditions of the liver and in primary liver cancers. The observation that some hepatocellular carcinomas (HCCs) express a biliary-like immunophenotype has led to the identification of HPCs in HCC. Accumulating evidence suggests that HPCs play a role as the cell of origin in a variety of primary liver cancers. This has led to the development of revolutionary concepts in hepatocarcinogenesis. In this article, the role and significance of HPCs in HCC, including its classification, are summarized and discussed.postprin

Role of hepatitis B virus X protein in liver cancer

published_or_final_versio

Virus-Clip: a fast and memory-efficient viral integration site detection tool at single-base resolution with annotation capability

Viral integration into the human genome upon infection is an important risk factor for various human malignancies. We developed viral integration site detection tool called Virus-Clip, which makes use of information extracted from soft-clipped sequencing reads to identify exact positions of human and virus breakpoints of integration events. With initial read alignment to virus reference genome and streamlined procedures, Virus-Clip delivers a simple, fast and memory-efficient solution to viral integration site detection. Moreover, it can also automatically annotate the integration events with the corresponding affected human genes. Virus- Clip has been verified using whole-transcriptome sequencing data and its detection was validated to have satisfactory sensitivity and specificity. Marked advancement in performance was detected, compared to existing tools. It is applicable to versatile types of data including whole-genome sequencing, whole-transcriptome sequencing, and targeted sequencing. Virus-Clip is available at http://web.hku.hk/~dwhho/Virus-Clip.zip.published_or_final_versio

Hormonal control of the metabolic machinery of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most fatal malignancies worldwide. It is an aggressive cancer with low cure rate, frequent metastasis, and highly resistant to conventional chemotherapies. Better knowledge regarding the molecular and metabolic alterations in HCC will be instrumental to the development of novel therapeutic interventions against HCC. In the August 2015 issue of Hepatology, Nie et al. reports an important molecular pathway that contributes to the Warburg Effect in HCC. They have beautifully demonstrated that the loss of a component of a hormonal system, the mineralocorticoid receptor (MR), reprogrammed the metabolic machinery of HCC cells to aerobic glycolysis through the miR-338-3p-PKL/R axis. The implication could be that in addition to drugs that directly target the metabolic enzymes in cancer cells, more translational efforts could be focused on the development of drugs that involve the activation of the MR-aldosterone system or other hormonal systems to target the Warburg effect.published_or_final_versio

TCGA whole-transcriptome sequencing data reveals significantly dysregulated genes and signaling pathways in hepatocellular carcinoma

This study systematically evaluates the TCGA whole-transcriptome sequencing data of hepatocellular carcinoma (HCC) by comparing the global gene expression profiles between tumors and their corresponding nontumorous liver tissue. Based on the differential gene expression analysis, we identified a number of novel dysregulated genes, in addition to those previously reported. Top-listing upregulated (CENPF and FOXM1) and downregulated (CLEC4G, CRHBP, and CLEC1B) genes were successfully validated using qPCR on our cohort of 65 pairs of human HCCs. Further examination for the mechanistic overview by subjecting significantly upregulated and downregulated genes to gene set enrichment analysis showed that different cellular pathways were involved. This study provides useful information on the transcriptomic landscape and molecular mechanism of hepatocarcinogenesis for development of new biomarkers and further in-depth characterization

Do statins reduce the risk of hepatocellular carcinoma in patients with chronic hepatitis B?

In subjects with chronic hepatitis B (CHB), the lifetime risk of developing hepatocellular carcinoma (HCC) is estimated to be 25-37 times compared to non-infected subjects. The process of hepatocarcinogenesis is complex and involves well-documented host, viral, and environmental risk factors. The most important risks include host factors such as older age, male gender, the presence of cirrhosis, and viral factors such as the viral load, genotype, and the presence of basal core promoter mutations. To date, antiviral therapy is the only intervention demonstrated to significantly reduce the risk of HCC development in CHB patients. Although oxidative stress has been implicated in cancer development, there is no established benefit shown from treatment with antioxidizing agents such as silymarin, green tea, and vitamin E.published_or_final_versio