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Abstract Cancer cells can evade immune elimination by activating immunosuppressive signaling pathways in the tumor microenvironment (TME). Targeting immunosuppressive signaling pathways to promote antitumor immunity has become an attractive strategy for cancer therapy. Aurora-A is a well-known oncoprotein that plays a critical role in tumor progression, and its inhibition is considered a promising strategy for treating cancers. However, targeting Aurora-A has not yet got a breakthrough in clinical trials. Recent reports have indicated that inhibition of oncoproteins may reduce antitumor immunity, but the role of tumor-intrinsic Aurora-A in regulating antitumor immunity remains unclear. In this study, we demonstrated that in tumors with high lymphocyte infiltration (hot tumors), higher tumor-intrinsic Aurora-A expression is associated with a better prognosis in CRC patients. Mechanically, tumor-intrinsic Aurora-A promotes the cytotoxic activity of CD8+ T cells in immune hot CRC via negatively regulating interleukin-16 (IL-16), and the upregulation of IL-16 may impair the therapeutic effect of Aurora-A inhibition. Consequently, combination treatment with IL-16 neutralization improves the therapeutic response to Aurora-A inhibitors in immune hot CRC tumors. Our study provides evidence that tumor-intrinsic Aurora-A contributes to anti-tumor immunity depending on the status of lymphocyte infiltration, highlighting the importance of considering this aspect in cancer therapy targeting Aurora-A. Importantly, our results suggest that combining Aurora-A inhibitors with IL-16-neutralizing antibodies may represent a novel and effective approach for cancer therapy, particularly in tumors with high levels of lymphocyte infiltration.

Abstract A wide variety of primary and secondary lymphoma types involves the skin. However, reports with comparisons between both groups are limited in Taiwan. We retrospectively enrolled all cutaneous lymphomas and evaluated their clinicopathologic features. There were 221 cases of lymphoma: 182 (82.3%) primary and 39 (17.7%) secondary. Mycosis fungoides was the most common primary T‐cell lymphoma, 92 (41.7%) cases, followed by CD30‐positive T‐cell lymphoproliferative disorders including lymphomatoid papulosis (n = 33, 14.9%) and cutaneous anaplastic large cell lymphoma (n = 12, 5.4%). The most frequent primary B‐cell lymphomas were marginal zone lymphoma (n = 8, 3.6%) and diffuse large B‐cell lymphoma (DLBCL), leg type (n = 8, 3.6%). DLBCL including variants was the most common secondary lymphoma involving skin. Most primary lymphomas presented at low‐stage (T‐cell, 86%; B‐cell, 75%), whereas the majority of secondary lymphomas presented at high‐stage (T‐cell, 94%; B‐cell, 100%). Patients with secondary lymphomas had an older mean age, more frequent B symptoms, lower serum albumin and hemoglobin, and a higher frequency of atypical lymphocytes in blood than those with primary lymphomas. In primary lymphomas, older age, lymphoma types, decreased lymphocyte counts and atypical lymphocytes in blood were poorer prognostic factors. In secondary lymphoma patients, lymphoma types, high serum lactate dehydrogenase and low hemoglobin levels predicted poorer survival. We found that the distribution of primary cutaneous lymphomas in Taiwan mirrors that of other Asian countries but shows some differences as compared with Western countries. Primary cutaneous lymphomas have a better prognosis than secondary lymphomas. Histologic classification of lymphomas highly correlated with disease presentation and prognosis.

Glioblastoma (GBM), the most aggressive form of brain cancer, is characterized by rapid growth and resistance to conventional therapies. Current treatments offer limited effectiveness, leading to poor survival rates and the need for novel therapeutic strategies. Arylquin 1 has emerged as a potential therapeutic candidate because of its unique mechanism of inducing apoptosis in cancer cells without affecting normal cells. This study investigated the efficacy of Arylquin 1 against GBM using the GBM8401 and A172 cells by assessing its dose-dependent cytotoxicity, apoptosis induction, and synergy with radiotherapy. In vitro assays demonstrated a significant reduction in cell viability and increased apoptosis, particularly at high concentrations of Arylquin 1. Migration and invasion analyses revealed notable inhibition of cellular motility. In vivo experiments on NU/NU nude mice with intracranially implanted GBM cells revealed that Arylquin 1 substantially reduced tumor growth, an effect magnified by concurrent radiotherapy. These findings indicate that by promoting apoptosis and enhancing radiosensitivity, Arylquin 1 is a potent therapeutic option for GBM treatment.

Epstein–Barr virus–related hemophagocytic lymphohistiocytosis (EBV-HLH) is a life-threatening hyperinflammatory syndrome. Although etoposide-based immunochemotherapy has improved survival rates, consensus regarding the appropriate salvage therapy for patients with refractory or relapsed EBV-HLH is lacking. We performed a retrospective study to examine the efficacy of a lymphoma-based treatment regimen for children with refractory or relapsed EBV-HLH. The data of six children were analyzed. Four had cytogenetic abnormalities, and two experienced a transition to EBV-positive T-cell lymphoma. They were treated with an intensive chemotherapy regimen modified from that used in the Berlin–Frankfurt–Münster Group Trial as salvage therapy. Five patients (83%) achieved complete response. Four patients (67%) were disease free for a median of 10 years without undergoing allogeneic hematopoietic stem cell transplantation. No grade 3 or 4 nonhematologic adverse events occurred. Lymphoma-based chemotherapy is a potential curative treatment for some subgroups of children with refractory or relapsed EBV-HLH.

Background and Objectives: Lung cancer is a leading cause of cancer mortality in Taiwan. With rapid advancement of targeted therapeutics in non-small cell lung cancers, next-generation sequencing (NGS) is becoming an important tool for biomarker testing. In this study, we describe institutional experience of NGS analysis in non-small cell carcinoma (NSCLC). Materials and Methods: A cohort of 73 cases was identified from the institutional pathology archive in the period between November 2020 and December 2022. Results: Adenocarcinoma was the most common histologic type (91.8%). Most patients presented with stage IIIB and beyond (87.7%). Twenty-nine patients (39.7%) were evaluated at the time of initial diagnosis, while the others had received prior chemotherapy or targeted therapy. The most frequently mutated gene was EGFR (63%), and this was followed by TP53 (50.7%), KRAS (13.7%), RB1 (13.7%), and CDKN2A (13.7%). Clinically actionable mutations associated with a guideline-suggested targeted therapy were identified in 55 cases (75.3%) overall, and in 47.1% of cases excluding EGFR TKI-sensitizing mutation. Biomarkers other than EGFR TKI-sensitizing mutations were compared. Cases without TKI-sensitizing EGFR mutation had more level 1 or 2 biomarkers (excluding EGFR TKI-sensitizing mutations) than cases with TKI-sensitizing EGFR mutations (47.1% versus 20.1%, p = 0.016). Progressive disease was associated with co-occurrence of clinically actionable mutations (20.5% versus 0%, p < 0.05). Eight of the nine cases with co-occurring actionable genetic alternations had an EGFR mutation. After an NGS test, 46.1% of actionable or potentially actionable genetic alternations led to patients receiving a matched therapy. Conclusions: Our study demonstrated that NGS analysis identifies therapeutic targets and may guide treatment strategies in NSCLC. NGS tests may be advantageous over multiple single-gene tests for optimization of treatment plans, especially for those with non-EGFR mutations or those with progressive disease.

Abstract Introduction Earlier studies have shown that lymphomatous effusions in patients with diffuse large B-cell lymphoma (DLBCL) are associated with a very poor prognosis, even worse than for non-effusion-associated patients with stage IV disease. We hypothesized that certain genetic abnormalities were associated with lymphomatous effusions, which would help to identify related pathways, oncogenic mechanisms, and therapeutic targets. Methods We compared whole-exome sequencing on DLBCL samples involving solid organs (n = 22) and involving effusions (n = 9). We designed a mutational accumulation-based approach to score each gene and used mutation interpreters to identify candidate pathogenic genes associated with lymphomatous effusions. Moreover, we performed gene-set enrichment analysis from a microarray comparison of effusion-associated versus non-effusion-associated DLBCL cases to extract the related pathways. Results We found that genes involved in identified pathways or with high accumulation scores in the effusion-based DLBCL cases were associated with migration/invasion. We validated expression of 8 selected genes in DLBCL cell lines and clinical samples: MUC4, SLC35G6, TP53BP2, ARAP3, IL13RA1, PDIA4, HDAC1 and MDM2, and validated expression of 3 proteins (MUC4, HDAC1 and MDM2) in an independent cohort of DLBCL cases with (n = 31) and without (n = 20) lymphomatous effusions. We found that overexpression of HDAC1 and MDM2 correlated with the presence of lymphomatous effusions, and HDAC1 overexpression was associated with the poorest prognosis. Conclusion Our findings suggest that DLBCL associated with lymphomatous effusions may be associated mechanistically with TP53-MDM2 pathway and HDAC-related chromatin remodeling mechanisms.

Abstract Diffuse large B-cell lymphoma (DLBCL) may present initially in bone marrow, liver and spleen without any lymphadenopathy (referred to as BLS-type DLBCL), which is aggressive and frequently associated with hemophagocytic syndrome. Its tumorigenesis and molecular mechanisms warrant clarification. By gene microarray profiling with bioinformatics analysis, we found higher expression of the stem cell markers HOXA9 and NANOG, as well as BMP8B, CCR6 and S100A8 in BLS-type than conventional DLBCL. We further validated expression of these markers in a large cohort of DLBCL including BLS-type cases and found that expression of HOXA9 and NANOG correlated with inferior outcome and poor prognostic parameters. Functional studies with gene-overexpressed and gene-silenced DLBCL cell lines showed that expression of NANOG and HOXA9 promoted cell viability and inhibited apoptosis through suppression of G2 arrest in vitro and enhanced tumor formation and hepatosplenic infiltration in a tail-vein-injected mouse model. Additionally, HOXA9-transfected tumor cells showed significantly increased soft-agar clonogenic ability and tumor sphere formation. Interestingly, B cells with higher CCR6 expression revealed a higher chemotactic migration for CCL20. Taken together, our findings support the concept that tumor or precursor cells of BLS-type DLBCL are attracted by chemotaxis and home to the bone marrow, where the microenvironment promotes the expression of stem cell characteristics and aggressiveness of tumor cells.

The pro-inflammatory cytokine IL-20 promotes tumor growth in several cancer types. Here, the authors show that high levels of IL-20 are associated with poor survival in patients with pancreatic ductal adenocarcinoma (PDAC) and that IL-20 blockade reduces tumor growth and alleviates cachexia symptoms in mouse models of PDAC.

Background: Interleukin-24 (IL-24) binds to two kinds of receptor complexes, namely IL-20R1/IL-20R2 and IL-20R2/IL-22R1, which are also bound by IL-20. IL-20 plays a detrimental role in liver fibrosis. Due to the sharing of receptor complexes, we aimed to determine whether IL-24 also participates in liver fibrosis. Methods: Clinical biopsy specimens from various stages of liver fibrosis were used to analyze IL-24 expression. IL-24 protein was administered to mice with thioacetamide (TAA)-induced liver injury. The direct effects of IL-24 on mouse primary hepatocytes or hepatic stellate cells (HSCs) were analyzed. Wild-type, IL-20R1-, and IL20R2-deficient mice were used to establish a model of acute TAA-induced liver injury. Findings: Among patients with more severe liver fibrosis, there was a reduced IL-24/IL-20 ratio. Administration of IL-24 protein protected mice from TAA-induced liver injury and reduction of liver inflammation by antioxidant effects. IL-24 protected hepatocytes from TAA-induced apoptosis and prevented liver fibrosis through the inhibition of the HSCs activation. The protective role of IL-24 acted on liver cells were mainly IL-20R1-independent. IL-20R2-deficient mice exhibited more severe liver injury upon TAA treatment, thus confirming the protective role of IL-24. Interpretation: IL-24 plays a key protective role in the progression of liver injury and has therapeutic potential for treating liver injuries. Funding: This work was supported by the Ministry of Science and Technology of Taiwan (MOST 106–2320-B-006–024) and Taiwan Liver Disease Prevention & Treatment Research Foundation.

Cancer: A regulator of cell cycle gene expression An RNA-binding protein contributes to cancer by boosting the protein-making potential of various genes involved in the cell cycle and cell division. Researchers in Taiwan led by Liang-Yi Hung from the National Cheng Kung University in Tainan, Taiwan, previously showed that a cancer-causing protein implicated in tumors of the colon and elsewhere gets induced by both an RNA-binding protein called hnRNP Q1 and a growth factor called EGF. Now, they have demonstrated that these two molecules work in concert to boost the efficiency by which the RNA encoding the cancer-causing protein gets translated into the protein. They also showed that hnRNP Q1 serves a similar RNA-modulating function for several genes involved in spindle checkpoint during cell division. Together, the findings point to hnRNP Q1 as a potential target for future anti-cancer drugs.

Background: Cutaneous lymphomas (CLs) have not been well characterized in Taiwan. Methods: We retrospectively reviewed the clinical and pathologic findings of cases of CLs of our department diagnosed from January 2001 to December 2010. The final diagnosis was made according to the 2008 World Health Organization (WHO) classification and its 2016 update. Results: Our series consisted of 91 primary CLs, 27 secondary CLs. The primary CLs consisted of 84 cases of mature T-cell and NK-cell lymphomas (CTCLs) and 7 cases of B-cell lymphomas, including mycosis fungoides (MF) (57.1%), lymphomatoid papulosis (LyP) (14.3%), anaplastic large cell lymphoma (7.7%), extranodal NK/T cell lymphoma, nasal type (4.4%), extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (3.3%), and diffuse large B-cell lymphoma (4.4%). Most MF (82.6%) cases were early MF (stage I–IIA) and were treated successfully, mainly with ultraviolet B (UVB) 311. The overall 5-year survival rate was 90.7% for early stage MF, 37.5% for stage late MF and 74.9% for all MF cases. Conclusion: Compared to other larger Western and Asian series of primary CLs, our series showed higher proportions of CTCLs and MF. Over 80% of MF was early MF, a finding consistent with the trend in early diagnosis of MF in recent decades. A nation-wide study is warranted to further characterize CLs in Taiwan.

Lymphocytic interstitial pneumonia (LIP) is an uncommon interstitial lung disease that is characterized by an interstitial infiltrate of lymphoplasmacytic cells. While idiopathic LIP appears to be extremely rare, most reported cases of LIP have been associated with coexisting immune derangements, particularly autoimmune diseases such as Sjögren's syndrome. In this report, we describe the presentation of LIP in a patient with underlying mixed connective tissue disease. Keywords: Lymphocytic interstitial pneumonia, Mixed connective tissue disease

Primary effusion lymphoma (PEL) is a rare subtype of non‐Hodgkin's lymphoma. PEL is closely related in pathogenesis to human herpesvirus 8 (HHV‐8) and typically occurs in patients with significant immunodeficiency. Cases of PEL in patients without either HIV infection or transplantation have been reported from HHV‐8‐endemic areas, but very rarely from the Asia‐Pacific region. In this case series, we describe the clinical and immunohistochemical presentations of four patients in southern Taiwan who were diagnosed with HHV‐8‐related PEL. All four patients were HIV‐negative and had not received organ transplantation. To our knowledge, this is the first authentic report of HIV‐unrelated PEL from the ethnically Chinese population. Considering the non‐specific clinical manifestations, the pivotal roles of specific assays for correct diagnosis, and the dismal prognosis of PEL, it is important for clinicians to include PEL as one of the differential diagnosis when approaching HIV‐uninfected patients with unexplained exudative body cavity effusion.

Placental mesenchymal dysplasia (PMD) and partial hydatidiform mole (PHM) placentas share similar characteristics, such as placental overgrowth and grape-like placental tissues. Distinguishing PMD from PHM is critical because the former can result in normal birth, while the latter diagnosis will lead to artificial abortion. Aneuploidy and altered dosage of imprinted gene expression are implicated in the pathogenesis of PHM and also some of the PMD cases. Diandric triploidy is the main cause of PHM, whereas mosaic diploid androgenetic cells in the placental tissue have been associated with the formation of PMD. Here, we report a very special PMD case also presenting with trophoblast hyperplasia phenotype, which is a hallmark of PHM. This PMD placenta has a normal biparental diploid karyotype and is functionally sufficient to support normal fetal growth. We took advantage of this unique case to further dissected the potential common etiology between these two diseases. We show that the differentially methylated region (DMR) at NESP55, a secondary DMR residing in the GNAS locus, is significantly hypermethylated in the PMD placenta. Furthermore, we found heterozygous mutations in NLRP2 and homozygous variants in NLRP7 in the mother’s genome. NLRP2 and NLRP7 are known maternal effect genes, and their mutation in pregnant females affects fetal development. The variants/mutations in both genes have been associated with imprinting defects in mole formation and potentially contributed to the mild abnormal imprinting observed in this case. Finally, we identified heterozygous mutations in the X-linked ATRX gene, a known maternal–zygotic imprinting regulator in the patient. Overall, our study demonstrates that PMD and PHM may share overlapping etiologies with the defective/relaxed dosage control of imprinted genes, representing two extreme ends of a spectrum.

Juvenile xanthogranuloma (JXG) belongs to the group of non-Langerhans cell histiocytosis. JXG is typically factor XIIIa- and CD68-positive. Nonlipidized JXG (NJXG) is a rare, mononuclear variant of JXG that shows few or absence of foam cells or Touton giant cells in the histiocytic infiltrate. Herein, we describe an unusual case of NJXG in a 7-year-old boy presenting with a 1-month history of a flesh-colored nodule on the forehead. The lesion was factor XIIIa-positive and CD68-negative but CD163-positive. Our case illustrates that CD163, a more specific marker of macrophage and monocyte differentiation, is a valuable marker for the diagnosis of NJXG.

Primary bone marrow lymphoma is an extremely rare disease. Its unusual clinical manifestations, such as hemophagocytic syndrome, frequently delay correct disease diagnosis, thus postponing treatment. Here, we reported a 76-year-old woman presenting with intermittent night fever and jaundice for 2 weeks, accompanied with hepatosplenomegaly and pancytopenia. Despite antibiotics treatment, the patient's fever persisted. Computed tomography showed hepatosplenomegaly without lymphadenopathy, and bone marrow aspiration and biopsy revealed a large B-cell lymphoma (LBCL) with hemophagocytic lymphohistiocytosis (HLH). After chemotherapy with rituximab, cyclophosphamide, vincristine, and prednisolone, both jaundice and pancytopenia recovered to normal. After 6 cycles of chemotherapy, the patient remained in complete remission for 18 months after diagnosis. Our experience indicates that clinicians should consider performing a timely bone marrow examination on patients with unknown fever and pancytopenia, particularly given that delayed diagnosis of primary bone marrow lymphoma can make treatment of this rare disease substantially more challenging.

Virus-associated human cancers may exhibit two characteristic histopathologic features: (1) the inflammation-rich background as observed in Epstein–Barr virus-associated Hodgkin lymphoma (HL) and nasopharyngeal carcinoma (NPC); and (2) the characteristic nuclear morphology such as the Reed-Sternberg cells in HL. Besides, the hepatocytes of chronic hepatitis B virus (HBV) infection frequently exhibit characteristic ground glass hepatocytes, a phenomenon associated with endoplasmic reticulum stress response induced by the overloaded or malfolded HBV surface antigens. In this review, we explore specifically the pathogenesis of Epstein–Barr virus-associated HL and NPC, and HBV-associated hepatocellular carcinoma based on the observed histopathologic features. We propose that the retention of viral proteins induces inflammation, endoplasmic reticulum stress, and genomic instability in HL, NPC, and hepatocellular carcinoma, whereby the viral oncoproteins may play additional transactivational roles to induce host genes for transformation, invasion, and metastasis. Therapeutic implications based on the pathogenesis of virus-associated cancers are discussed.

The appropriate management of hematology patients depends first on correct diagnoses. Expert review is important in reaching accurate diagnoses. To improve diagnostic accuracy, the Taiwan Society of Pathology and the Taiwan Division of the International Academy of Pathology has been conducting an expert consultation program for general pathologists since 2001. As per this program, we have received a total of 395 cases (406 samples) for review. We found that meaningful diagnostic discrepancies occurred frequently in hematopathology reviews. Ambiguous or nondiagnostic original reports were the major causative factor for the major discrepancy cases, which demonstrates that diagnostic uncertainty is a big problem for referring pathologists. However, the World Health Organization lymphoma classification may be poorly reproducible in countries where extensive use of an ancillary technique is not used by general pathologists. This review is intended to report the misdiagnoses most commonly seen in the hematopathology practice in Taiwan. Awareness of the easily misinterpreted entities helps to achieve the right diagnosis and improve patient care.

BACKGROUND:Accurate, rapid, and early diagnosis of dengue virus (DENV) infections is essential for optimal clinical care. Here, we evaluated the efficacy of the quantitative real-time PCR (qRT-PCR)-LightMix dengue virus EC kit for DENV detection using samples from a dengue outbreak in Taiwan in 2015. METHODS:Sera from patients with suspected DENV infection were analyzed and compared using the LightMix kit, a Dengue NS1 Ag + Ab Combo kit for detection of NS1 antigen and DENV-specific IgM and IgG antibodies, and an "in-house" qualitative DENV-specific RT-PCR assay. RESULTS:A total of 8,989, 8,954, and 1581 samples were subjected to NS1 antigen detection, IgM and IgG detection, and LightMix assays, respectively. The LightMix assay yielded a linear curve for viral loads (VL) between 102 and 106 copies/reaction, and the minimum detection limits for DENV serotype 1 (DENV1) and DENV2, DENV3, and DENV4 were 1, 10, and 100 focus forming units (FFU)/mL, respectively. There was 88.9% concordance between the results obtained using the NS1 antigen combo kit and by LightMix analysis, and the diagnostic sensitivity and specificity of the two methods were 89.4 and 100%, and 84.7 and 100%, respectively. Notably, fatal cases were attributed to DENV2 infection, and 79.5% (27/34) of these cases occurred in patients ≥ 71 years of age. Among these older patients, 82.3% (14/17) were NS1/IgM/IgG (+/-/-), exhibiting VLs between 106-109 copies/mL, which was markedly higher than the rate observed in the other age groups. CONCLUSIONS:The LightMix assay was effective for early diagnosis of DENV infection. Our data indicate that high VLs during primary infection in elderly patients may be a positive predictor for severe illness, and may contribute to high mortality rates.

Quantitation of cytomegalovirus (CMV) viral load in the transplant patients has become a standard practice for monitoring the response to antiviral therapy. The cut-off values of CMV viral load assays for preemptive therapy are different due to the various assay designs employed. To establish a sensitive and reliable diagnostic assay for preemptive therapy of CMV infection, two commercial automated platforms including m2000sp extraction system integrated the Abbott RealTime (m2000rt) and the Roche COBAS AmpliPrep for extraction integrated COBAS Taqman (CAP/CTM) were evaluated using WHO international CMV standards and 110 plasma specimens from transplant patients. The performance characteristics, correlation, and workflow of the two platforms were investigated. The Abbott RealTime assay correlated well with the Roche CAP/CTM assay (R2 = 0.9379, P

Lymphoma-specific biomarkers contribute to therapeutic strategies and the study of tumorigenesis. Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma. However, only 50% of patients experience long-term survival after current treatment; therefore, developing novel therapeutic strategies is warranted. Comparative proteomic analysis of two DLBCL lines with a B-lymphoblastoid cell line (LCL) showed differential expression of Ran GTPase-activating protein 1 (RanGAP1) between them, which was confirmed using immunoblotting. Immunostaining showed that the majority of DLBCLs (92%, 46/50) were RanGAP1(+), while reactive lymphoid hyperplasia (n = 12) was RanGAP1(+) predominantly in germinal centers. RanGAP1 was also highly expressed in other B-cell lymphomas (BCL, n = 180) with brisk mitotic activity (B-lymphoblastic lymphoma/leukemia: 93%, and Burkitt lymphoma: 95%) or cell-cycle dysregulation (mantle cell lymphoma: 83%, and Hodgkin's lymphoma 91%). Interestingly, serum RanGAP1 level was higher in patients with high-grade BCL (1.71 ± 2.28 ng/mL, n = 62) than in low-grade BCL (0.75 ± 2.12 ng/mL, n = 52) and healthy controls (0.55 ± 1.58 ng/mL, n = 75) (high-grade BCL vs. low-grade BCL, p = 0.002; high-grade BCL vs. control, p < 0.001, Mann-Whitney U test). In vitro, RNA interference of RanGAP1 showed no effect on LCL but enhanced DLBCL cell death (41% vs. 60%; p = 0.035) and cell-cycle arrest (G0/G1: 39% vs. 49%, G2/M: 19.0% vs. 7.5%; p = 0.030) along with decreased expression of TPX2 and Aurora kinases, the central regulators of mitotic cell division. Furthermore, ON 01910.Na (Estybon), a multikinase inhibitor induced cell death, mitotic cell arrest, and hyperphosphorylation of RanGAP1 in DLBCL cell lines but no effects in normal B and T cells. Therefore, RanGAP1 is a promising marker and therapeutic target for aggressive B-cell lymphoma, especially DLBCL.

Hypermethylation of the glutathione S-transferase π 1 (GSTP1) gene promoter region has been reported to be a potential biomarker to distinguish hepatocellular carcinoma (HCC) from other liver diseases. However, reports regarding how specific a marker it is have ranged from 100% to 0%. We hypothesized that, to a large extent, the variation of specificity depends on the location of the CpG sites analyzed. To test this hypothesis, we compared the methylation status of the GSTP1 promoter region of the DNA isolated from HCC, cirrhosis, hepatitis, and normal liver tissues by bisulfite-PCR sequencing. We found that the 5' region of the position -48 nt from the transcription start site of the GSTP1 gene is selectively methylated in HCC, whereas the 3' region is methylated in all liver tissues examined, including normal liver and the HCC tissue. Interestingly, when DNA derived from fetal liver and 11 nonhepatic normal tissue was also examined by bisulfite-PCR sequencing, we found that methylation of the 3' region of the promoter appeared to be liver-specific. A methylation-specific PCR assay targeting the 5' region of the promoter was developed and used to quantify the methylated GSTP1 gene in various diseased liver tissues including HCC. When we used an assay targeting the 3' region, we found that the methylation of the 5'-end of the GSTP1 promoter was significantly more specific than that of the 3'-end (97.1% vs. 60%, p

Ectomesenchymal chondromyxoid tumor (ECMT) is a rare entity of the dorsal tongue first described in 1995. Herein, we report a rare case of lingual ECMT in a 41-year-old man. Patient presented with an asymptomatic, small nodule (0.5 cm in diameter) in the anterior tongue. The pathological findings showed uni-lobular proliferation of fusiform cells, arranged in net-like sheets or swirls, in a chondromyxoid background. The tumor cells were immunoreactive for S-100 and glial fibrillary acidic protein (GFAP), but negative for epithelial markers. Familiarity with this entity helps pathologists make a correct diagnosis.