BRAF(V600E) was not limited to LCH and was detected more frequently in histiocytic sarcoma. Our findings suggest that the BRAF pathway may contribute to the pathogenesis or malignant transformation of histiocytic and dendritic cell neoplasms.

Tristetraprolin (TTP) is an AU‐rich element‐binding protein that regulates mRNA stability. Here, we report that TTP suppress the growth of human colon cancer cells both in vivo and in vitro by regulating of the expression of vascular endothelial growth factor (VEGF). TTP protein expression in human colonic tissues was markedly decreased in colonic adenocarcinoma compared with in normal mucosa and adenoma. VEGF expression was higher in colonic adenocarcinoma than in normal mucosa and adenoma. Specific inhibition of TTP expression by RNA‐interference increased the expression of VEGF in cultured human colon cancer cells, and TTP overexpression markedly decreased it. In addition, elevated expression of TTP decreased the expression level of luciferase linked to a 3′ terminal AU‐rich element (ARE) of VEGF mRNA. Colo320/TTP cells overexpressing TTP grew slowly in vitro and became tumors small in size when xenografted s.c into nude mice. These findings demonstrate that TTP acts as a negative regulator of VEGF gene expression in colon cancer cells, suggesting that it can be used as novel therapeutic agent to treat colon cancer.

Background: The aim of study was to determine the relative frequency of malignant lymphoma according to World Health Organization (WHO) classification in Korea. Methods: A total of 3,998 cases diagnosed at 31 institutes between 2005 and 2006 were enrolled. Information including age, gender, pathologic diagnosis, site of involvement and immunophenotypes were obtained. Results: The relative frequency of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) was 95.4% and 4.6%, respectively. B-cell lymphomas accounted for 77.6% of all NHL, while T/ natural killer (T/NK)-cell lymphomas accounted for 22.4%. The most frequent subtypes of NHL were diffuse large B-cell lymphoma (42.7%), extranodal marginal zone B-cell lymphoma (MZBCL) of mucosa-associated lymphoid tissue (19.0%), NK/T-cell lymphoma (6.3%) and peripheral T-cell lymphoma (PTCL), unspecified (6.3%), in decreasing order. The relative frequency of HL was nodular sclerosis (47.4%), mixed cellularity (30.6%), and nodular lymphocyte predominant (12.1%) subtypes. Compared with a previous study in 1998, increase in gastric MZBCL and nodular sclerosis HL, and slight decrease of follicular lymphoma, PTCL, and NK/T-cell lymphoma were observed. Conclusions: Korea had lower rates of HL and follicular lymphoma, and higher rates of extranodal NHL, extranodal MZBCL, and NK/T-cell lymphoma of nasal type compared with Western countries. Changes in the relative frequency of lymphoma subtypes are likely ascribed to refined diagnostic criteria and a change in national health care policy.

Programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) are new therapeutic targets in cancer immunotherapy. The aim of this study was to investigate the clinicopathological characteristics of PD-1 and PD-L1 expression in extranodal natural killer/T‑cell lymphoma, nasal type (ENKTL). We performed PD-1 and PD-L1 immunostaining in 79 ENKTL biopsy samples and retrospectively analyzed medical records of all 79 patients from four tertiary referral hospitals. The expression of PD-1 and PD-L1 by tumor cells and/or infiltrating immune cells was evaluated. The expression rates of PD-L1 in tumor cells and infiltrating immune cells were 79.7 and 78.5 %, respectively, whereas PD-1 in tumor cells and infiltrating immune cells were 1.3 and 11.4 %. The PD-L1 positivity in tumor cells and infiltrating immune cells was significantly associated with low international prognostic index (IPI) (P = 0.044 and 0.037, respectively). Patients with normal range of serum lactate dehydrogenase demonstrated a significantly higher PD-L1 positivity in tumor cells (P = 0.020). PD-L1-positive patients had a trend toward better overall survival compared with that in patients with PD-L1-negative in tumor cells and infiltrating immune cells (P = 0.498 and 0.435, respectively). The expression rate of PD-L1 was up to 79.7 % in ENKTL, while PD-1 expression rate was very low. This is the first report describing the clinicopathological features and survival outcome according to expression of PD-1 and PD-L1 in ENKTL.

Epstein-Barr virus (human herpesvirus-4) is very common virus that can be detected in more than 95% of the human population. Most people are asymptomatic and live their entire lives in a chronically infected state (IgG positive). However, in some populations, the Epstein-Barr virus (EBV) has been involved in the occurrence of a wide range of B-cell lymphoproliferative disorders (LPDs), including Burkitt lymphoma, classic Hodgkin’s lymphoma, and immune–deficiency associated LPDs (post-transplant and human immunodeficiency virus–associated LPDs). T-cell LPDs have been reported to be associated with EBV with a subset of peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphomas, extranodal nasal natural killer/T-cell lymphomas, and other rare histotypes. This article reviews the current evidence covering EBV-associated LPDs based on the 2016 classification of the World Health Organization. These LPD entities often pose diagnostic challenges, both clinically and pathologically, so it is important to understand their unique pathophysiology for correct diagnoses and optimal management.

Tristetraprolin (TTP) and let-7 microRNA exhibit suppressive effects on cell growth through down-regulation of oncogenes. Both TTP and let-7 are often repressed in human cancers, thereby promoting oncogenesis by derepressing their target genes. However, the precise mechanism of this repression is unknown. We here demonstrate that p53 stimulated by the DNA-damaging agent doxorubicin (DOX) induced the expression of TTP in cancer cells. TTP in turn increased let-7 levels through down-regulation of Lin28a. Correspondingly, cancer cells with mutations or inhibition of p53 failed to induce the expression of both TTP and let-7 on treatment with DOX. Down-regulation of TTP by small interfering RNAs attenuated the inhibitory effect of DOX on let-7 expression and cell growth. Therefore, TTP provides an important link between p53 activation induced by DNA damage and let-7 biogenesis. These novel findings provide a mechanism for the widespread decrease in TTP and let-7 and chemoresistance observed in human cancers.

A 58-year-old woman was referred to our hospital due to progressive skin darkening, which began 5 months previously. The patient had strikingly diffuse blue-gray discoloration of the skin, most prominent in sun-exposed areas, especially her face and hands. The oral mucosa, tongue, gums, eye conjunctiva, ears, nail beds, and trunk were also involved. Bluish-gray discoloration of all nails was aggravated by cold weather. She had ingested 1 L of colloidal silver solution daily for approximately 16 months as a traditional remedy. Her serum silver concentration was 381 ng/ml which was a very high (reference level: <15 ng/ml). Light microscopic examination of a punch biopsy specimen from her nose revealed fine, minute, round, and brown-black granules deposited in the basement membrane of hair follicular epithelium. Scanning electron microscopic examination showed electron-dense granules deposited in the intercellular space of sweat glands. Energy disperse X-ray spectrometry analysis demonstrated peaks for silver and sulfur in the dense black deposits. The ingestion of colloidal silver appears to be an increasing practice among patients using alternative health practices. All silver-containing products including colloidal silver should be labeled with a clear warning to prevent argyria, especially in alternative health practices.

Heat shock protein (Hsp) in tumor cells has been proposed to enhance their resistance to chemotherapeutic agents. In the present study, we investigated the influence of Hsp expression on the irinotecan resistance of human colorectal cancer cells. Among eight Hsp genes tested in this study, we confirmed that the expression of Hsp27 correlated with irinotecan resistance in colorectal cancer cells. Specific inhibition of Hsp27 expression using an antisense oliogodeoxynucleotide increased the irinotecan sensitivity. On the contrary, an overexpression of Hsp27 decreased the irinotecan sensitivity in colorectal cancer cells. Elevated expression of Hsp27 decreased caspase-3 activity in colorectal cancer cells. The expression level of Hsp27 determined by immunohistochemical analysis correlated with the clinical response to irinotecan in colorectal cancer patients. Hsp27 expression levels of irinotecan-non-responder (mean staining score, 6.28; proportion of high staining score, 64.2%) were significantly higher compared to those of irinotecan-responder (mean staining score, 3.16; proportion of high staining score, 33.3%) (P for ttest = 0.045). These findings suggest that Hsp27 is involved in the irinotecan resistance of colorectal cancer cells possibly by reducing caspase-3 activity.