POFUT1 acts as a tumor promoter in glioblastoma by enhancing the activation of Notch signaling.

Dysregulation of protein O-fucosyl transferase 1 (POFUT1) contributes to the occurrence and progression of multiple cancers. However, whether POFUT1 has a relationship with the pathogenesis of glioblastoma (GBM) is unknown. This work was aimed at evaluating the detailed relevance of POFUT1 in GBM. Here, we demonstrated high levels of POFUT1 in GBM tissue and elucidated that GBM patients with high levels of POFUT1 had a shorter survival rate than those with low levels of POFUT1. POFUT1 knockdown in GBM cells markedly downregulated the ability to proliferate and invade, while overexpression of POFUT1 potentiated the proliferative and invasive ability of GBM cells. Further mechanistic studies indicated that silencing POFUT1 prohibited the activation of Notch signaling, leading to a reduction in the expression of HES1 and HEY1. On the contrary, overexpression of POFUT1 enhanced the activation of Notch signaling. Notably, inhibition of Notch signaling markedly reversed POFUT1-overexpression-induced tumor promotion effects in GBM cells. In addition, POFUT1 silencing markedly repressed the potential of GBM cells to form tumors in vivo. In conclusion, the data of this work indicates that POFUT1 serves a tumor promotion role in GBM by enhancing the activation of Notch signaling. This study underlines the potential role of the POFUT1/Notch axis in GBM progression and proposes POFUT1 as a promising anticancer target for GBM.

Role of FUT8 expression in clinicopathology and patient survival for various malignant tumor types: a systematic review and meta-analysis.

Dysregulation of α(1,6)-fucosyltransferase (FUT8) plays significant roles in development of a variety of malignant tumor types. We collected as many relevant articles and microarray datasets as possible to assess the prognostic value of FUT8 expression in malignant tumors. For this purpose, we systematically searched PubMed, Embase, Web of Science, Springer, Chinese National Knowledge Infrastructure (CNKI), and Wan Fang, and eventually identified 7 articles and 35 microarray datasets (involving 6124 patients and 10 tumor types) for inclusion in meta-analysis. In each tumor type, FUT8 expression showed significant (p< 0.05) correlation with one or more clinicopathological parameters; these included patient gender, molecular subgroup, histological grade, TNM stage, estrogen receptor, progesterone receptor, and recurrence status. In regard to survival prognosis, FUT8 expression level was associated with overall survival in non-small cell lung cancer (NSCLC), breast cancer, diffuse large B cell lymphoma, gastric cancer, and glioma. FUT8 expression was also correlated with disease-free survival in NSCLC, breast cancer, and colorectal cancer, and with relapse-free survival in pancreatic ductal adenocarcinoma. For most tumor types, survival prognosis of patients with high FUT8 expression was related primarily to clinical features such as gender, tumor stage, age, and pathological category. Our systematic review and meta-analysis confirmed the association of FUT8 with clinicopathological features and patient survival rates for numerous malignant tumor types. Verification of prognostic value of FUT8 in these tumor types will require a large-scale study using standardized methods of detection and analysis.

Exosomal MALAT1 sponges miR-26a/26b to promote the invasion and metastasis of colorectal cancer via FUT4 enhanced fucosylation and PI3K/Akt pathway.

BACKGROUND: Exosomes are vesicles of endocytic origin released by various cell types and emerging as important mediators in tumor cells. Human metastases-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA known to promote cell proliferation, metastasis, and invasion in colorectal cancer (CRC). METHODS: The expression of MALAT1 was analyzed in CRC using qRT-PCR. FUT4 and fucosylation levels were detected in CRC clinical samples and CRC cell lines by immunofluorescent staining, western blot and lectin blot analysis. CRC derived exosomes were isolated and used to examine their tumor-promoting effects in vitro and in vivo. RESULTS: The invasive and metastatic abilities of primary CRC cells were enhanced after exposure to exosomes derived from highly metastatic CRC cells, which increased the fucosyltransferase 4 (FUT4) levels and fucosylation not by directly transmitting FUT4 mRNA. Exosomal MALAT1 increased FUT4 expresssion via sponging miR-26a/26b. Furthermore, MALAT1/miR-26a/26b/FUT4 axis played an important role in exosome-mediated CRC progression. Exosomal MALAT1 also mediated FUT4-associated fucosylation and activated the PI3K/AKT/mTOR pathway. CONCLUSIONS: These data indicated that exosomal MALAT1 promoted the malignant behavior of CRC cells by sponging miR-26a/26b via regulating FUT4 and activating PI3K/Akt/mTOR pathway.

Long noncoding RNA AC114812.8 promotes the progression of bladder cancer through miR-371b-5p/FUT4 axis.

Bladder cancer (BC) brings a heavy burden to afflicted patients worldwide. In order to find new diagnostic markers and therapeutic targets for this disease, we investigated the role of a novel lncRNA, AC114812.8, in bladder cancer progression. Clone formation and CCK-8 assays were used to detect the proliferative capacity of the cells, and the transwell assay was used to explore their invasion and migration abilities. Wound healing experiments were also used to detect cell migration. Luciferase reporter assays were used to investigate the interactions between lncRNA, target gene and miRNA. The expression of FUT4 and marker genes related to epithelial-mesenchymal transition was explored through western blot analysis. Our findings revealed that AC114812.8 was significantly upregulated in BC and could markedly facilitate the proliferation, migration, and invasion of bladder cancer cells both in vitro and in vivo. Furthermore, duel-luciferase reporter assay revealed that AC114812.8 could regulate the FUT4 expression level by sponging miR-371b-5p to facilitate BC progression. We detected the levels of EMT-related biomarkers in AC114812.8-overexpressing BC cells by western blot analysis and found that AC114812.8 could promote EMT process. Rescue experiments showed that miR-371b-5p could rescue the effect of AC114812.8 on proliferation and metastasis of BC. Our results suggest that AC114812.8 could be a novel prognostic biomarker and therapeutic target for bladder cancer.

Engineering of α-1,3-fucosyltransferases for production of 3-fucosyllactose in Escherichia coli.

Fucosyllactoses (FLs), present in human breast milk, have been reported to benefit human health immensely. Especially, 3-fucosyllactose (3-FL) has numerous benefits associated with a healthy gut ecosystem. Metabolic engineering of microorganisms is thought to be currently the only option to provide an economically feasible route for large-scale production of 3-FL. However, engineering principles for α-1,3-fucosyltransferases (1,3-FTs) are not well-known, resulting in the lower productivity of 3-FL than that of 2'-fucosyllactose (2'-FL), although both 2'-FL and 3-FL follow a common pathway to produce GDP-L-fucose. The C-terminus of 1,3-FTs is composed of heptad repeats, responsible for dimerization of the enzymes, and a peripheral membrane anchoring region. It has long been thought that truncation of most heptad repeats, retaining just 1 or 2, helps the soluble expression of 1,3-FTs. However, whether the introduction of truncated version of 1,3-FTs enhances the production of 3-FL in a metabolically engineered strain, is yet to be tested. In this study, the effect of these structural components on the production of 3-FL in Escherichia coli was evaluated through systematic truncation and elongation of the C-terminal regions of three 1,3-FTs from Helicobacter pylori. Although these three 1,3-FTs contained heptad repeats and membrane-anchoring regions of varying lengths, they commonly exhibited an optimal performance when the number of heptad repeats was increased, and membrane-binding region was removed. The production of 3-FL could be increased 10-20-fold through this simple strategy.

C/EBPδ drives interactions between human MAIT cells and endothelial cells that are important for extravasation.

Many mediators and regulators of extravasation by bona fide human memory-phenotype T cells remain undefined. Mucosal-associated invariant T (MAIT) cells are innate-like, antibacterial cells that we found excelled at crossing inflamed endothelium. They displayed abundant selectin ligands, with high expression of FUT7 and ST3GAL4, and expressed CCR6, CCR5, and CCR2, which played non-redundant roles in trafficking on activated endothelial cells. MAIT cells selectively expressed CCAAT/enhancer-binding protein delta (C/EBPδ). Knockdown of C/EBPδ diminished expression of FUT7, ST3GAL4 and CCR6, decreasing MAIT cell rolling and arrest, and consequently the cells' ability to cross an endothelial monolayer in vitro and extravasate in mice. Nonetheless, knockdown of C/EBPδ did not affect CCR2, which was important for the step of transendothelial migration. Thus, MAIT cells demonstrate a program for extravasastion that includes, in part, C/EBPδ and C/EBPδ-regulated genes, and that could be used to enhance, or targeted to inhibit T cell recruitment into inflamed tissue.

AP1 mediates uPA/uPAR induced FUT4 expression and trophoblast invasion.

Trophoblast invasion is crucial for embryo implantation and successful pregnancy. Urokinase-type plasminogen activator (uPA)/urokinase-type plasminogen activator receptor (uPAR) are expressed on trophoblasts and involved in trophoblast invasion. The transcription factor activator protein 1 (AP1) (c-Fos and cJun) and fucosyltransferase IV (FUT4) have been found to be involved in this process. However, the relationship of uPA/uPAR, AP1 and FUT4 is unclear. The current study aimed to investigate the role of AP1 in uPA/uPAR induced FUT4 expression and trophoblast invasion. We found that p-c-Fos and p-c-Jun were decreased in abortion patients compared to that in normal pregnant women. Employing human trophoblastic cells, we then demonstrated that uPA/uPAR induced the expression of p-c-Fos and p-c-Jun. Applying an electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP), we further proved that transcription factor AP1 bound to FUT4 promoter that could increase FUT4 transcriptional activity, further promoting trophoblast cell migration and invasion through JNK MAPK signaling pathway. Taken together, these results suggest that uPA/uPAR induces FUT4 expression, and trophoblast cell invasion mediated by AP1 transcription factor (c-Fos and c-Jun). Our findings provide novel insights into the relationship between AP1 and abortion.

Analysis of CD15, CD57 and HIF-1α in biopsies of patients with peri-implantitis.

Peri-implantitis is an infectious disease characterized by inflammation of the tissues surrounding the implant, bleeding on probing with or without suppuration, and bone loss. Peri-implant lesions contain a leukocyte infiltrate of plasma cells, lymphocytes, macrophages and neutrophils. A survey of the literature did not show any studies reporting an association between hypoxia and peri-implantitis. The aim of the present cross-sectional study was to evaluate histological changes and immunostaining for CD15, CD57 and HIF-1α in the peri-implant mucosa of patients with and without peri-implantitis. Mucosal biopsies were obtained from 18 patients with peri-implantitis and 10 control subjects without peri-implantitis at a private health care center between 2010 and 2012. The sections were fixed in 10% buffered formalin, processed and embedded in paraffin for histopathological and immunohistochemical study. Acanthosis, spongiosis and exocytosis were observed in both groups, with no significant difference between them. The peri-implantitis group showed increased immunostaining for CD15, a neutrophil marker, and HIF-1α, a tissue hypoxia marker, but no significant difference in immunostaining for CD57, a Natural Killer cell marker. The increase in neutrophil (CD15) and hypoxia (HIF-1α) markers in patients with peri-implantitis suggests an active participation of neutrophils and hypoxia in the pathogenesis of this disease. Since the present study was the first to evaluate the expression of CD15, CD57 and HIF-1α in peri-implant tissues, further studies should be performed to better understand the role of these molecules in peri-implantitis.

Expression of embryonic stem cell markers in acute myeloid leukemia.

Acute myeloid leukemia is driven by leukemic stem cells which can be identified by cross lineage expression or arrest of differentiation compared to normal hematopoietic stem cells. Self-renewal and lack of differentiation are also features of stem cells and have been associated with the expression of embryonic genes. The aim of our study was to evaluate the expression of embryonic antigens (OCT4, NANOG, SOX2, SSEA1, SSEA3) in hematopoietic stem cell subsets (CD34+CD38- and CD34+CD38+) from normal bone marrows and in samples from acute myeloid leukemia patients. We observed an upregulation of the transcription factors OCT4 and SOX2 in leukemic cells as compared to normal cells. Conversely, SSEA1 protein was downregulated in leukemic cells. The expression of OCT4, SOX2, and SSEA3 was higher in CD34+CD38- than in CD34+CD38+ subsets in leukemic cells. There was no correlation with biological characteristics of the leukemia. We evaluated the prognostic value of marker expression in 69 patients who received an intensive treatment. The rate of complete remission was not influenced by the level of expression of markers. Overall survival was significantly better for patients with high SOX2 levels, which was unexpected because of the inverse correlation with favorable genetic subtypes. These results prompt us to evaluate the potential role of these markers in leukemogenesis and to test their relevance for better leukemic stem cell identification.

Expression of α-1,6-fucosyltransferase (FUT8) in rice grain and immunogenicity evaluation of plant-specific glycans.

Rice seed is a cost-effective bioreactor for the large-scale production of pharmaceuticals. However, convincing evidence of the immunogenicity of plant-specific glycans is still limited although plant-specific glycans are considered potential allergic antigens. In the present study, we found that the α-1,3-fucose content of the glycoprotein produced from rice seed was much lower than that in leaf, and conversely, a higher ß-1,2-xylose content was detected in seed than that in leaf. We detected the α-1,6-fucose content in the glutelin and recombinant human α1-antitrypsin (OsrAAT). The further results in a line containing AAT and FUT8 genes indicated that the α-1,6-fucose content of modified glycosylated recombinant α1-antitrypsin (mgOsrAAT) was 38.4%, while glutelin was only 6.8%. Interestingly, the α-1,3-fucose content of mgOsrAAT was significantly reduced by 59.8% compared with that of OsrAAT. Furthermore, we assessed the immunogenicity of OsrAAT, mgOsrAAT and human α1-antitrypsin (hAAT) using an animal system. The PCA results indicated no significant differences in the IgG, IgM and IgE titers among OsrAAT, mgOsrAAT and hAAT. Further studies revealed that those antibodies were mainly from α-1,3-fucose, but not from ß-1,2-xylose, indicating that α-1,3-fucose was the major immunogenic resource. Our results demonstrated that α-1,3-fucose contents in seed proteins was much less than that of leaf, and could not be a plant-specific glycan because it also exists in human proteins.

Stage-Specific Embryonic Antigen-1 (SSEA-1) Expression in Thyroid Tissues.

Stage-specific embryonic antigen-1 (SSEA-1), also known as CD15, is a member of a cluster of differentiation antigens that have been identified in various normal tissues and in different types of cancers including papillary and medullary thyroid carcinoma. SSEA-1 may be expressed in normal stem cells and cancer stem-like cells. To evaluate the potential diagnostic and prognostic utility of SSEA-1 in thyroid tumors, we analyzed the expression of SSEA-1 in normal and neoplastic thyroid tissues by immunohistochemistry (IHC) using a tissue microarray with 158 different tissue cores. To evaluate the potential utility of SSEA-1 as a surface marker, we also assessed the expression of SSEA-1 in thyroid cell lines by flow cytometric analysis. SSEA-1 immunoreactivity was identified in malignant thyroid follicular epithelial cancers but not in the benign thyroid tissues. Anaplastic thyroid (ATC) (80 %) and conventional papillary thyroid carcinoma (PTC) (60.7 %) showed significantly higher percentage of cases that were SSEA-1 immunoreactive than follicular variant of papillary thyroid carcinoma (FVPTC) (20.6 %) and follicular carcinoma (FCA) (32.1 %). Flow cytometric analysis of cultured thyroid cell lines showed that a small subpopulation of ATC and PTC thyroid tumor cells had SSEA-1 immunoreactivity which may represent thyroid cancer stem-like cells. The ATC cells expressed more SSEA-1 immunoreactive cells than the PTC cell lines. Our findings suggest that expression of SSEA-1 immunoreactivity in thyroid neoplasms was associated with more aggressive thyroid carcinomas. SSEA-1 is a marker that detects malignant thyroid neoplasms in formalin-fixed paraffin-embedded thyroid tissue sections and may be a useful marker for thyroid cancer stem-like cells.

Role of CD15 expression in dysplastic and neoplastic tissue of the bile duct - a potential novel tool for differential diagnosis of indeterminate biliary stricture.

BACKGROUND AND AIMS: CD15 is expressed by various cancer types; among these are intrahepatic and perihilar cholangiocarcinoma (CCA). The aim of this study was to elucidate CD15 expression in distal CCA as well as in dysplastic biliary tissue and to determine its prognostic significance. METHODS AND RESULTS: Tissue samples from patients with intrahepatic (iCCA, n = 22), perihilar (pCCA, n = 7) and distal CCA (dCCA, n = 15), who underwent surgical resection in the period from 2010 to 2015 were evaluated for CD15 expression. Tissue of synchronous lymph node metastasis (n = 13), CCA-associated dysplasia (n = 20), dysplasia in intraductal biopsies (n = 10) and benign proliferations (n = 12), as well as inflammatory biliary lesions (n = 28) and non-inflammatory bile ducts (n = 23), were evaluated equally for CD15 expression. CD15 was found to be expressed highly in iCCA (81.8%), pCCA (85.7%), dCCA (73.3%), CCA-associated dysplasia (70.0%), dysplasia in intraductal biopsies (100%) and metastatic tissue (84.6%). CD15 expression was negative in 58 of 64 benign bile duct alterations resulting in an overall sensitivity and specificity of CD15 in CCA of 80.7 and 90.6% patients, respectively. CD15 expression was correlated significantly with a decreased overall survival in patients with CD15-positive CCA associated dysplasia (P = 0.003). However, CD15 expression in the invasive tumour component was not correlated with clinical outcome. CONCLUSION: CD15 is a sensitive and specific marker for intraepithelial and invasive neoplasias of the bile duct. Therefore, it can be helpful in the delineation of dysplastic and neoplastic biliary cells from non-neoplastic tissue, which frequently causes a diagnostic problem in indeterminate biliary stricture.

Fucosyltransferase 8 expression in breast cancer patients: A high throughput tissue microarray analysis.

The aim of this study was to compare the expression of fucosyltransferase 8 (FUT8) in breast cancer tissue and to investigate the relationship between this marker with tumor progression and its applicability to differential diagnosis. An immunohistochemical study was performed for FUT8 using the tissue microarray technique. In addition, the mRNA and protein levels of FUT8 in the tissue were also tested by real-time PCR and Western blot. There was a significant difference in cytoplasmic expression of FUT8 between breast cancer tissue and matched normal tissue (p<0.001). The percent of FUT8 staining in breast cancer tissues ranging from negative, weak positive, positive and strong positive were 2.7%, 40.2%, 54% and 3.2%, respectively. High FUT8 protein expression correlated with lymphatic metastasis (p=0.008) and with stage status (p=0.039). We detected that reduced FUT8 expression correlated with disease-free survival (p=0.02) and overall survival (p=0.04) of breast cancer patients. Expression of FUT8 can stratify breast cancer tissue and may be considered a prognostic marker for breast cancer patients.

Increased fucosylation has a pivotal role in multidrug resistance of breast cancer cells through miR-224-3p targeting FUT4.

Fucosylation is the final step in the glycosylation machinery, which produces glycans involved in tumor multidrug resistance development. MicroRNAs (miRNAs) are endogenous negative regulators of gene expression and have been implicated in most cellular processes of tumors, including drug resistance. This study was undertaken to determine the roles of fucosylation and miR-224-3p in multidrug resistance of human breast cancer cell lines. Comparative analysis revealed differential modification patterns of fucosylation of the fucosylated N-glycans in drug-resistant T47D/ADR cells and sensitive line T47D cells. The expressional profiles of fucosyltransferase genes in two pairs of parental and chemoresistant human breast cancer cell lines showed that FUT4 was up-regulated highly in MDR cell lines. Altered level of FUT4 affected the drug-resistant phenotype of T47D and T47D/ADR cells both in vitro and in vivo. By bioinformatics analysis, we identified FUT4 as one of the miR-224-3p-targeted genes. Further studies showed an inverse relationship between of FUT4 and miR-224-3p in parental and ADR-resistant breast cancer cells, wherein miR-224-3p was downregulated in resistant cells. 3'-UTR dual-luciferase reporter assay confirmed that miR-224-3p directly targeted 3'-untranslation region (3'-UTR) of FUT4 mRNA. In addition, miR-224-3p overexpression sensitized T47D/ADR cells to chemotherapeutics and reduced the growth rate of breast cancer xenografts in vivo. Our results indicate that FUT4 and miR-224-3p are crucial regulators of cancer response to chemotherapy, and may serve as therapeutic targets to reverse chemotherapy resistance in breast cancer.

Cancer-related CD15/FUT4 overexpression decreases benefit to agents targeting EGFR or VEGF acting as a novel RAF-MEK-ERK kinase downstream regulator in metastatic colorectal cancer.

BACKGROUND: Cancer-related immune antigens in the tumor microenvironment could represent an obstacle to agents targeting EGFR "cetuximab" or VEGF "bevacizumab" in metastatic colorectal cancer (mCRC) patients. METHODS: Infiltrating immune cells into tumor tissues, cancer-related expression of immune antigens (CD3, CD8, CD68, CD73, MPO, CD15/FUT4) from 102 mCRC patients receiving first-line Cetuximab or Bevacizumab plus chemotherapy were assessed by immunohistochemistry and validated in an independent tissue microarrays of 140 patients. Genome-wide expression profiles from 436 patients and 60 colon cancer cell lines were investigated using bioinformatics analysis. In vitro kinase assays of target genes activated by chemokines or growth factors were performed. RESULTS: Here, we report that cancer-related CD15/FUT4 is overexpressed in most of mCRCs patients (43 %) and associates with lower intratumoral CD3+ and CD8+ T cells, higher systemic inflammation (NLR at diagnosis >5) and poorer outcomes, in terms of response and progression-free survival than those CD15/FUT4-low or negative ones (adjusted hazard ratio (HR) = 2.92; 95 % CI = 1.86-4.41; P < 0.001). Overexpression of CD15/FUT4 is induced through RAF-MEK-ERK kinase cascade, suppressed by MEK inhibitors and exhibits a close connection with constitutive oncogenic signalling pathways that respond to ERBB3 or FGFR4 activation (P < 0.001). CD15/FUT4-high expressing colon cancer cells with primary resistance to cetuximab or bevacizumab are significantly more sensitive to MEK inhibitors than CD15/FUT4-low counterparts. CONCLUSION: Cancer-related CD15/FUT4 overexpression participates in cetuximab or bevacizumab mechanisms of resistance in mCRC patients. CD15/FUT4 as a potential target of the antitumor immune response requires further evaluation in clinical studies.

Baicalin promotes embryo adhesion and implantation by upregulating fucosyltransferase IV (FUT4) via Wnt/beta-catenin signaling pathway.

Glycosylation plays a significant role in determining the receptivity of the uterine endometrium to embryo. Fucosyltransferase IV (FUT4) is expressed stage-specifically in the uterine endometrium of mammalians, and considered as a marker of the endometrial receptivity. Baicalin, a monomer of flavonoids, is known to have functions in improving reproduction. However, the mechanism by which baicalin regulates the expression of FUT4 in embryo-endometrium adhesion remains unclear. Our results showed that baicalin significantly increased FUT4 mRNA and protein expression levels both in human endometrial cells and mouse endometrial tissue, and consistently elevated embryo adhesion rate during implantation in vitro and embryonic implantation competence in pregnant mouse. This study suggests that baicalin facilitates endometrial reproduction via elevating FUT4 expression through Wnt/ß-catenin signaling pathway.

Fucosyltransferase IV (FUT4) as an effective biomarker for the diagnosis of breast cancer.

Specific enzymes are involved in altered glycosylation of cancer. Fucosyltransferase IV (FUT4) is associated with the proliferation and metastasis of breast cancer. The application of FUT4 assay in the serum has not been reported yet. Here, the expression level of FUT4 in the breast cancer patient's tissues (n=60) was analyzed by immunohistochemistry (IHC) and the secreted FUT4 in blood serum samples (n=225) was detected by enzyme-linked immunosorbent assay (ELISA). Using low metastatic MCF-7 and high metastatic MDA-MB-231 breast cancer cell lines, FUT4 expression was also detected by reverse transcription-polymerase chain reaction (RT-PCR), Western blot and immunofluorescent staining. The conventional cancer biomarkers cancer antigen (CA15.3) and carcinoembryonic antigen (CEA) was analyzed by Elecsys-electrochemical immune assay (ECLIA) to compare specificity and sensitivity with that of FUT4. We have observed a significant high expression of FUT4 in breast cancer tissues and serums as compared to the normal tissues (P<0.01) and control serums (P<0.05). FUT4 expression was increased in MDA-MB-231 cells vs. that in MCF-7 cells. Furthermore, the results of receiver operating characteristic (ROC) analysis was shown, area under curve of FUT4 (AUC=0.784) was higher than that of CA15.3 (AUC=0.468) and CEA (AUC=0.563). The relation analysis is indicated FUT4 is significantly correlated with CA15.3 (r=0.234, P<0.05) and there is no significant correlation with CEA. In conclusion, this study suggests that FUT4 can serve as novel biomarker in the diagnosis and prognosis of breast cancer.

HBME-1 and CD15 immunocytochemistry in the follicular variant of thyroid papillary carcinoma.

Papillary carcinoma is the most common thyroid malignancy. As the cytological diagnosis of papillary carcinoma is not difficult in patients with the usual type of lesion, fine-needle aspiration (FNA) cytology is an effective method for preoperative evaluation. However, this modality is often ineffective in identifying the follicular variant of papillary thyroid carcinoma (FVPTC) due to its similarity to other follicular lesions and the incompleteness of typical nuclear features. Therefore, we investigated the expression of immunocytochemical markers of papillary carcinoma in cytological specimens of FVPTC and evaluated their utilities. The immunoreactivity of HBME-1 and CD15 was investigated using 50 imprint smear cytological specimens obtained from thyroid lesions, including 13 FVPTC. The sensitivity and specificity of HBME-1 for FVPTC were 92% and 89%, respectively, while those of CD15 were 23% and 100%, respectively. In conclusion, HBME-1 is a sensitive marker of papillary carcinoma, including both usual type and FVPTC, in cytological specimens. Therefore, using HBME-1 immunocytochemistry in FNA cytology will lead to reduction of the incidence of false-negative diagnoses of FVPTC. Although CD15 is apparently inferior in terms of sensitivity for FVPTC, its excellent specificity will support the definitive diagnosis of thyroid malignancies, including FVPTC, after screening with HBME-1.

Acquisition of CD30 and CD15 accompanied with simultaneous loss of all pan-T-cell antigens in a case of histological transformation of mycosis fungoides with involvement of regional lymph node: an immunophenotypic alteration resembling classical Hodgkin lymphoma.

: Acquired expression of CD30 is frequently noted in histological transformation of mycosis fungoides (MF), but simultaneous gain of CD15 accompanied with loss of pan-T-cell antigens are extremely rare. We report an unusual case of transformed MF with such an immunophenotypic alteration resembling classical Hodgkin lymphoma. The patient was an 81-year-old male with MF, who was initially treated with topical steroids and phototherapy. Despite the initial response, the patient developed a tumor-like skin lesion that was confirmed to be CD30-positive large T-cell lymphoma and was subsequently found to have a regional lymph node involvement by pleomorphic large cell lymphoma. Besides CD30, pleomorphic large cells were positive for CD15 but negative for all B cell- and T cell-specific antigens. Epstein-Barr virus was negative. Polymerase chain reaction-based assays demonstrated a clonal rearrangement of T-cell receptor gamma gene but detected no B-cell clone. The mechanism and clinical significance of this phenotypic conversion remains to be elucidated.