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Summary: Peripheral T‐cell lymphomas (PTCL) are morphologically and biologically heterogeneous and a subset expresses CD30, including anaplastic large cell lymphomas (ALCL) and a minority of PTCL, not otherwise specified (PTCL, NOS). ALCL with ALK translocations (ALCL, ALK+) are readily identified by routine diagnostic methods, but differentiating ALCL without ALK translocation (ALCL, ALK−) and PTCL, NOS expressing CD30 (PTCL CD30+) can be challenging. Furthermore, rare PTCL co‐express CD30 and CD15 (PTCL CD30+CD15+); some resemble ALCL, ALK− while others resemble classic Hodgkin lymphoma. To explore the relationship between PTCL CD30+CD15+ and ALCL, ALK−, we analysed 19 cases of PTCL with CD30 expression, previously diagnosed as ALCL, ALK− (nine cases) and PTCL CD30+CD15+ (10 cases) for DUSP22/IRF4 rearrangements, coding RNA expression and selected transcriptome analysis using the NanoString nCounter gene expression analysis platform. Unsupervised clustering showed no clear segregation between ALCL, ALK− and PTCL CD30+CD15+. Three cases previously classified as PTCL CD30+CD15+ showed DUSP22/IRF4 rearrangements, favouring a diagnosis of ALCL, ALK−. Our results suggest that cases previously designated PTCL CD30+CD15+, likely fall within the spectrum of ALCL, ALK−; additionally, a subset of ALCL, ALK− with DUSP22/IRF4 rearrangement expresses CD15, consistent with previous reports and expands the immunophenotypic spectrum of this lymphoma subgroup. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of a combination of Tarantula cubensis alcohol extract (TCAE) and capecitabine (CAP) in the treatment of azoxymethane (AOM)-induced colorectal cancer (CRC). Methods: Forty-two Wistar albino rats were divided into 7 groups with 6 rats in each group. The groups consisted of Control (C), Control+TCAE (C-TCAE), Control+CAP (C-CAP), Cancer control (CC), Cancer+TCAE (CC-TCAE), Cancer+CAP (CC-CAP) and Cancer+CAP+TCAE (CC-CAP+TCAE). To induce CRC, AOM (15 mg/kg) was administered to rats subcutaneously (sc) twice at a one-week interval to all the groups except control. From the 15th week, TCAE (0.2 mL/rat sc) was administered to CC-TCAE group every 3 days for 4 weeks, and CAP (40 mg/kg/day) was administered by gavage to CC-CAP group for 4 weeks. In CC-CAP+TCAE group, TCAE (0.2 mL/rat sc) was administered every 3 days for 4 weeks, and CAP (40 mg/kg/day) was administered gavage for 4 weeks. Animals were treated for 18 weeks. Aberrant crypt foci (ACF) were evaluated histopathologically among CC, CC-TCAE, CCCAP, and CC-CAP+TCAE groups. ß-catenin, CD15, Proliferating Cell Nuclear Antigen (PCNA), and Nuclear Factor kappa B (NF-κB) expression levels were immunohistochemically compared among all groups. Results: Histopathologically, ACF scores were significantly increased in CC group, while a significant decrease in the relevant scores (p < 0.001) was observed in CC-CAP and CC-CAP+TCAE treatment groups, and the lowest scores were in CC-CAP+TCAE group. Immunohistochemically, in CC group, ß-catenin, Nuclear Factor kappa B (NF-κB), Proliferating Cell Nuclear Antigen (PCNA) and CD15 expressions were highly irregular. CC-CAP and CC-CAP+TCAE groups had significantly reduced expressions (p < 0.001), and the lowest expressions were in CC-CAP+TCAE group. Conclusion: The combined use of TCAE and CAP in treatment of CRC has a synergistic effect and increases the anticancer efficacy of TCAE, and CAP. More studies at the molecular level are needed in the future to demonstrate the clinical benefit of TCAE supplementation during the treatment of CRC with CAP. [ABSTRACT FROM AUTHOR]

Introduction: Medulloblastoma, an embryonal small round blue cell tumor primarily arising in the posterior fossa, is the most common malignancy of the central nervous system in children and requires intensive multi-modality therapy for cure. Overall 5-year survival is approximately 75% in children with primary disease, but outcomes for relapsed disease are very poor. Recent advances have identified molecular subgroups with excellent prognosis, with 5-year overall survival rates >90%, and subgroups with very poor prognosis with overall survival rates

Background: The histopathology and CD15 expression in large for gestational age (LGA) placentas is not well-documented. Methods: To analyze this, we utilized 2 separate cohorts of placentas from singleton term deliveries. LGA and appropriate for gestational age (AGA) placentas were compared for major histopathologies including acute and chronic inflammation, maternal and fetal vascular malperfusion, delayed villous maturation (DVM), and villous hypervascularity/chorangiosis. We also examined CD15 immunohistochemistry in LGA and AGA placentas. Stained slides were reviewed blinded to the placental weight. Five random 20× fields were scored semi-quantitatively for CD15 staining of villous capillaries on a scale of 0 to 5 (0 = 0%, 1 = 1%-5%, 2 = 5%-25%, 3 = 25%-50%, 4 = 50%-75%, and 5 = >75%). Results: In 1 cohort, 1238 LGA and 7908 AGA placentas were identified. Patients with LGA placentas were significantly more likely to have higher birthweight babies, obesity, hypertensive disorders, pre-gestational, and gestational diabetes. Also, LGA placentas had a higher prevalence of fetal vascular malperfusion, DVM, and villous chorangiosis. In other cohort of 75 LGA placentas and 73 AGA controls, the average score of CD15 staining in villous capillaries was significantly higher amongst LGA placentas. Conclusion: We conclude that LGA placentas have increased expression of CD15 in villous capillary endothelium and higher prevalence of FVM, DVM, and villous chorangiosis than AGA placentas. [ABSTRACT FROM AUTHOR]

The glycan moiety Lewis X (LeX) has been implicated in defining progenitor cells as well as playing a role in the progression of solid tumors, including breast cancer. Here, we used the original stage-specific embryonic antigen-1 (SSEA-1) antibody, MC-480, targeting the LeX motif to examine the expression pattern of this marker within the context of a differentiation hierarchy as well as functional properties of breast cancer cells. Immunohistochemical staining revealed the presence of SSEA-1 in a progenitor zone in the normal breast gland. In breast cancer, 81 of 220 carcinomas (37%) were positive for SSEA-1 and a distinct pattern could be correlated to major subtypes. Specifically, estrogen receptor alpha (ERα)-negative tumors showed a higher frequency of SSEA-1 expression compared to ERα-positive tumors, which are generally considered more differentiated (56% vs 29%, p <0.005). Functional assays performed on two representative breast cancer cell lines demonstrated that SSEA-1-expressing cells exhibited cancer stem cell properties as well as having more invasive potential, regardless of ERα status. A potential role of SSEA-1 in metastasis was confirmed by pairwise staining of primary- and corresponding lymph node tumors. Altogether, our data suggest that expression of SSEA-1 in breast cancer contributes to the malignant phenotype: [ABSTRACT FROM AUTHOR]

Simple Summary: A common issue in glioblastoma stem cells (GSCs) studies is the need to efficiently and precisely target GSCs using reliable biomedical markers. Using single-cell RNA sequencing datasets, we quantitatively evaluated an extensive number of GSCs markers with multiple parameters that dictate the feasibility of various laboratory and therapeutic applications. We present promising marker candidates with their scores on the corresponding parameters and apply sequential selection based on these parameters. Both previously approved and novel markers are proposed according to the evaluation. We demonstrate the possibility of choosing a biomedical marker in a nonarbitrary way and provide quantitative references for potential GSCs markers. Targeting glioblastoma (GBM) stem-like cells (GSCs) is a common interest in both the laboratory investigation and clinical treatment of GBM. Most of the currently applied GBM stem-like markers lack validation and comparison with common standards regarding their efficiency and feasibility in various targeting methods. Using single-cell RNA sequencing datasets from 37 GBM patients, we obtained a large pool of 2173 GBM stem-like marker candidates. To evaluate and select these candidates quantitatively, we characterized the efficiency of the candidate markers in targeting the GBM stem-like cells by their frequencies and significance of being the stem-like cluster markers. This was followed by further selection based on either their differential expression in GBM stem-like cells compared with normal brain cells or their relative expression level compared with other expressed genes. The cellular location of the translated protein was also considered. Different combinations of selection criteria highlight different markers for different application scenarios. By comparing the commonly used GSCs marker CD133 (PROM1) with markers selected by our method regarding their universality, significance, and abundance, we revealed the limitations of CD133 as a GBM stem-like marker. Overall, we propose BCAN, PTPRZ1, SOX4, etc. for laboratory-based assays with samples free of normal cells. For in vivo targeting applications that require high efficiency in targeting the stem-like subtype, the ability to distinguish GSCs from normal brain cells, and a high expression level, we recommend the intracellular marker TUBB3 and the surface markers PTPRS and GPR56. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are promising carriers for the delivery of a variety of chemical and biological drugs. However, their efficacy is limited by the lack of cellular specificity. Available methods to improve the tissue specificity of EVs predominantly rely on surface display of proteins and peptides, largely overlooking the dense glycocalyx that constitutes the outermost layer of EVs. In the present study, we report a reconfigurable glycoengineering strategy that can endogenously display glycans of interest on EV surface. Briefly, EV producer cells are genetically engineered to co‐express a glycosylation domain (GD) inserted into the large extracellular loop of CD63 (a well‐studied EV scaffold protein) and fucosyltransferase VII (FUT7) or IX (FUT9), so that the engineered EVs display the glycan of interest. Through this strategy, we showcase surface display of two types of glycan ligands, sialyl Lewis X (sLeX) and Lewis X, on EVs and achieve high specificity towards activated endothelial cells and dendritic cells, respectively. Moreover, the endothelial cell‐targeting properties of sLeX‐EVs were combined with the intrinsic therapeutic effects of mesenchymal stem cells (MSCs), leading to enhanced attenuation of endothelial damage. In summary, this study presents a reconfigurable glycoengineering strategy to produce EVs with strong cellular specificity and highlights the glycocalyx as an exploitable trait for engineering EVs. [ABSTRACT FROM AUTHOR]

Abstract Extracellular vesicles (EVs) are promising carriers for the delivery of a variety of chemical and biological drugs. However, their efficacy is limited by the lack of cellular specificity. Available methods to improve the tissue specificity of EVs predominantly rely on surface display of proteins and peptides, largely overlooking the dense glycocalyx that constitutes the outermost layer of EVs. In the present study, we report a reconfigurable glycoengineering strategy that can endogenously display glycans of interest on EV surface. Briefly, EV producer cells are genetically engineered to co‐express a glycosylation domain (GD) inserted into the large extracellular loop of CD63 (a well‐studied EV scaffold protein) and fucosyltransferase VII (FUT7) or IX (FUT9), so that the engineered EVs display the glycan of interest. Through this strategy, we showcase surface display of two types of glycan ligands, sialyl Lewis X (sLeX) and Lewis X, on EVs and achieve high specificity towards activated endothelial cells and dendritic cells, respectively. Moreover, the endothelial cell‐targeting properties of sLeX‐EVs were combined with the intrinsic therapeutic effects of mesenchymal stem cells (MSCs), leading to enhanced attenuation of endothelial damage. In summary, this study presents a reconfigurable glycoengineering strategy to produce EVs with strong cellular specificity and highlights the glycocalyx as an exploitable trait for engineering EVs.

Background: Gastric cancer is one of the main causes of mortality due to malignancy. Tumor-associated neutrophil (TAN) has an immunosuppressor role and is related to prognosis. But the mechanism is unknown. The present study investigated the role of CD15 (TAN) in gastric cancer. Methods and Materials: Our study was cross-sectional and made on 40 recognized patients of gastric cancer. Immunohistochemical staining for CD15 was done on gastric cancer tissues. Tumor behaviors were estimated by histopathological assessments. Results: CD15 positivity was revealed in 17 (42.5%) of all evaluated patients. The evaluation of the connection between CD15 expression and demographic data and tumor characteristics revealed no significant relationship between CD15 expression and patients' sex, age, tumor site, and size, subtype of tumor, tumor grade and stage, perineural invasion, and lymphovascular invasion (Pvalue> 0.05). Conclusion: Gastric cancer prognosis is related to diverse immune cells in the tumor microenvironment but in our society, the CD15 expression hasn't any relationship with aggressive histopathologic features of this tumor. [ABSTRACT FROM AUTHOR]

Leukocytoclastic vasculitis is an inflammatory disease of small blood vessels; circulating immune complexes are part of the disease. A 57-year-old female presented with a sudden appearance of palpable purpura with petechial hemorrhages on the lower limbs after taking multiple medications. Skin biopsies were stained for H&E, direct immunofluorescence (DIF) and immunohistochemistry (IHC). The DIF revealed strong staining with multiple immunoglobulins and other markers in small dermal blood vessels, including those around skin appendices The IHC was positive for myeloperoxidase. CD15, myeloperoxidase and HLA-DPDQDR on the upper dermal blood vessels, as well as on inflammatory cells and debris around the vessels. These findings have not been previously documented and may indicate that circulating immune complexes activate the neutrophils. [ABSTRACT FROM AUTHOR]

Analysis of T lymphocyte proliferation and activation after antigenic or mitogenic stimulation is a vital parameter used in the diagnosis of various immuno-deficiencies and during the monitoring of treatment responses. Most applied techniques are based on the incorporation of tritiated thymidine (3HTdR) or ELISPOT analysis, both rely on rather time-consuming/-intensive ex vivo protocols or encompass inherent drawbacks such as the inability to distinguish specific cell populations (3H-TdR, ELISPOT) or focus on a single cytokine (ELISPOT). Here we aimed at characterizing the rapid expression of intracellular CD154 (CD40L) as a marker for rare antigen-specific CD4+ T cells in pemphigus vulgaris (PV). Upon stimulation with human desmoglein (Dsg) 3, the major autoantigen in PV, the expression of CD154 was significantly increased in PV patients compared to healthy controls (HC) and correlated with anti-Dsg3 IgG titers. Patients with active disease showed higher numbers of Dsg3-reactive CD4+ T cells in CXCR5+ T follicular helper cells. In remittent PV and HC, CXCR5+CD4+ T cells remained largely unaffected by Dsg3. IL-17 and IL-21 expression were significantly induced only in CD154+CD4+ T cells from PV patients, lending themselves as potential novel treatment targets. Additionally, stimulation with immunodominant Dsg3-derived epitopes strongly induced a CD4+ T cell response via CD40-CD154 interaction similar to the human Dsg3 protein. We here established a rapid ex vivo assay allowing the detection of Dsg3-reactive CD4+ T cells from activated systemically available PBMCs, which further supports the crucial concept of antigenspecific T cells in the pathogenesis of PV. [ABSTRACT FROM AUTHOR]

Background: Avelumab is a human antibody that targets the programmed cell death ligand-1 (PD-L1) protein in cancer cells. Novel anticancer therapies for renal cell carcinoma (RCC) consider cluster of differentiation 15 (CD15) and interleukin 17 receptor A (IL-17RA) as potential targets. Notably, the expression of PD-L1, CD15 and IL-17RA is dependent on signal transducer and activator of transcription 3 (STAT3)., Objectives: The aim of the study was to investigate whether targeting PD-L1 with avelumab alters the expression levels of CD15 and IL-17RA, and to assess the STAT3-mediated regulation of CD15 and IL-17RA., Material and Methods: We applied immunocytochemistry (ICC) and confocal laser scanning (CLS) microscopy to assess the expression and localization of the immunotherapy targets in 3 renal cancer cell lines and 1 healthy renal cell line., Results: After treatment with 20 ng/mL avelumab, renal cancer cells showed a reduction in STAT3 expression. The expression of CD15 increased in cancer cells that exhibited a high level of IL-17RA, and the membrane signal of CD15 was reduced. In other renal cancer cell lines, the expression of CD15 decreased. Conversely, the level of IL-17RA changed only in healthy renal cells after treatment with avelumab, with no impact on renal cancer cells., Conclusions: Our study suggests that the targeting of PD-L1 with avelumab alters the expression of CD15 and IL-17RA, which play an important prognostic and therapeutic role in novel anticancer therapy.

Leukocyte adhesion deficiency type II (LAD II, also known as SLC35C1‐congenital disorder of glycosylation) is an autosomal recessive disorder characterized by growth and cognitive impairment, peripheral neutrophilia, recurrent infections, and the Bombay blood phenotype. A subset of patients with a milder presentation has been described with short stature and developmental delay but minimal immune and hematologic features. Some patients with LAD II benefit from oral fucose therapy, though this has not been previously studied in patients with milder disease. In this study, we describe two new patients from separate families with the milder variant of LAD II and review the published literature on this rare disorder. We demonstrate improvement in speech and cognition, CD15 expression, and core fucosylation of serum glycoproteins after 27 months of oral fucose supplementation in one patient. These patients further support the stratification of this disorder into distinct subtypes, a classical severe and an attenuated variant, and provide preliminary evidence of benefit of fucose therapy in the latter group. [ABSTRACT FROM AUTHOR]

Simple Summary: CD15 (Lewis X) is a typical myeloid antigen presented in myeloid and monocytic lineages of cells. This molecule interacts with E-, L- and P-selectins, which allows for adhesion with endothelial cells. CD15 is found on various cancer cells, including renal cancer, prostate and bladder cancers, acute leukaemias, hepatocellular carcinoma, breast cancer and melanoma cells. Its high expression can serve as a prognostic marker for patients and is a potentially valuable target for immunotherapy against cancer. Blockage of the antigen's function results in reduced metastatic potential and it may be an immunotherapeutic target. CD15s is a sialyl derivative of CD15; however, unlike the high expression of CD15, which is a prognostic factor in Hodgkin lymphoma, CD15s relates to poor prognosis for patients. CD15 is considered a marker of cancer stem cells. This review presents a comprehensive description of the prognostic role of CD15 and CD15s and their use in anticancer therapy. CD15 (Lewis X/Lex) is a fucosyl (3-fucosly-N-acetyl-lactosamine) moiety found on membrane proteins of various cancer cells. These cancers include renal cancer, prostate and bladder cancers, acute leukaemias, hepatocellular carcinoma, breast cancer and melanoma. The biological role of CD15 is interaction with E-, L- and P-selectins (adhesion molecules), allowing for adhesion with endothelial cells. In this way, cancer cells start to interact with the endothelia of blood vessels and consequently move out from the blood flow to the surrounding tissues. Blockage of the antigen's function results in reduced metastatic potential. Moreover, the molecule may be a therapeutic target against cancer in monoclonal antibody-based therapies. CD15 may serve as a prognostic marker for patients and there are high hopes for its use in the immunotherapeutic treatment of tumours. CD15s is a sialyl derivative of CD15 that possesses its own unique characteristics. Its soluble form may act as a competitive inhibitor of the interaction of cancer cells with epithelial cells and thus disallow migration through the vessels. However, the prognostic relevance of CD15 and CD15s expression is very complex. This review presents a comprehensive description of the role of CD15 and CD15s in cancer development and metastasis and overviews its significance for clinical applications. [ABSTRACT FROM AUTHOR]

BackgroundThe determination of skin wound vitality based on tissue sections is a challenge for the forensic pathologist. Histology is still the gold standard, despite its low sensitivity. Immunohistochemistry could allow to obtain a higher sensitivity. Upon the candidate markers, CD15 and myeloperoxidase (MPO) may allow to early detect polymorphonuclear neutrophils (PMN). The aim of this study was to evaluate the sensitivity and the specificity of CD15 and MPO, with glycophorin C co-staining, compared to standard histology, in a series of medicolegal autopsies, and in a human model of recent wounds.MethodsTwenty-four deceased individuals with at least one recent open skin wound were included. For each corpse, a post-mortem wound was performed in an uninjured skin area. At autopsy, a skin sample from the margins of each wound and skin controls were collected (n = 72). Additionally, the cutaneous surgical margins of abdominoplasty specimens were sampled as a model of early intravital stab wound injury (scalpel blade), associated with post-devascularization wounds (n = 39). MPO/glycophorin C and CD15/glycophorin C immunohistochemical double staining was performed. The number of MPO and CD15 positive cells per 10 high power fields (HPF) was evaluated, excluding glycophorin C—positive areas.ResultsWith a threshold of at least 4 PMN/10 high power fields, the sensitivity and specificity of the PMN count for the diagnostic of vitality were 16 and 100%, respectively. With MPO/glycophorin C as well as CD15/glycophorin C IHC, the number of positive cells was significantly higher in vital than in non-vital wounds (p < 0.001). With a threshold of at least 4 positive cells/10 HPF, the sensitivity and specificity of CD15 immunohistochemistry were 53 and 100%, respectively; with the same threshold, MPO sensitivity and specificity were 28 and 95%.ConclusionWe showed that combined MPO or CD15/glycophorin C double staining is an interesting and original method to detect early vital reaction. CD15 allowed to obtain a higher, albeit still limited, sensitivity, with a high specificity. Confirmation studies in independent and larger cohorts are still needed to confirm its accuracy in forensic pathology.

Oral ulcers constitute one of the most common chief complaints of patients attending any dental practice. The cause of oral mucosal ulceration is generally attributed to acute or chronic trauma from local factors. However, oral lesions may be the initial manifestation of many systemic conditions. Moreover, a group of oral ulcerative lesions have been reported to exhibit vast numbers of eosinophils and known as Traumatic Ulcerative Granuloma with Stromal Eosinophilia (TUGSE). We present two cases of oral ulcers which on microscopic examination exhibited numerous eosinophils from ulcerated epithelium to deep into the submucosa and an exuberant lymphoid proliferation. CD15 immunohistochemical marker was used in these cases to ease the identification of the eosinophils. We also highlight the differential diagnosis of TUGSE that may manifest as oral lesions, as an important diagnostic guide for clinicians in contemporary practice.

Background: Immunological abnormalities are implicated in the pathogenesis of inflammatory diseases of the uveal tract. Investigation of the molecular mechanisms of various forms of endogenous uveitis from the standpoint of current immunology seems to be relevant from the theoretical and practical standpoints. This will provide a direction for further research on the development of pathogenetically grounded methods of treatment of uveitis. Purpose: to assess the expression levels of lymphocyte activation markers, intercellular adhesion marker (ICAM)-1 CD54, CD95 (FAS), and CD5, and neutrophil activation marker CD15, in the peripheral blood of patients with intermediate uveitis and healthy individuals. Material and Methods: Blood samples were taken from 14 patients (mean age, 34.0 ± 11.0 years) with intermediate uveitis before treatment and 26 practically healthy individuals (mean age, 36.0 ± 10.0 years). An immunohistocytochemical study using monoclonal antibodies was employed to assess the expression. Results: Expression of cell surface molecular markers on peripheral blood lymphocytes was significantly higher in patients with intermediate uveitis compared with controls. Mean percentage and absolute values of CD54 (ICAM-1) expression were 29.6 ± 3.5% and 674.18 ± 63.4 cell/µL, respectively, for patients, versus 14.2 ± 3.1% and 674.18 ± 63.4 cell/µL, respectively, for controls; CD95 (FAS), 28.5 ± 4.9% and 534.2 ± 59.5 cell/µL, for patients, versus 18.9 ± 3.1% and 254.18 ± 42.1 cell/µL, respectively, for controls; CD5, 23.4 ± 4.1% and 622.8 ± 53.5 cell/µL, respectively, for patients, versus 10.3 ± 1.96% and 152.11 ± 10.13 cell/µL, respectively, for controls. CD15, a neutrophil activation marker, was significantly (Mann-Whitney test, p < 0.05) higher expressed in patients (mean percentage expression, 28.7 ± 5.8%; mean absolute expression, 980.19 ± 58.4 cell/µL), than in controls (mean percentage expression, 14.2 ± 3.1%; mean absolute expression, 165.5 ± 32.1 cell/µL). Increased expression of lymphocyte activation markers may indicate a failure of autotolerance mechanisms as well as excessive immune response leading to intraocular inflammation. In addition, increased expression of CD 54 (ICAM-1) and CD 95 (FAS) may be a prognostic sign for increased inflammation in the eye. Conclusion: Immunological status of patients with intermediate uveitis is characterized by significantly increased expression of molecular markers such as intercellular adhesion marker (ICAM)-1 CD54, apoptosis marker CD95 (FAS), lymphocyte autoactivation marker CD5, and neutrophil activation marker CD15. Further research of longitudinal changes in these characteristics may be important for predicting the course of inflammation over time and determining the therapy needed. [ABSTRACT FROM AUTHOR]

CD10 and CD15 expression has been reported in several tumors. Whether CD10 and CD15 have a role in colorectal mucinous and signet ring adenocarcinoma (MSA) tumorigenesis is not yet known. We aimed to investigate the role of CD10 and CD15 expression in mucinous colorectal adenoma-carcinoma sequence (ACS) and determine if there is any clinical and prognostic significance associated with their expression. Seventy-five cases of colorectal MSA, and 9 cases of adenoma samples were collected. Manual TMA blocks were constructed and immunohistochemistry for CD10 and CD15 was done. Compared to adenomas, CD15 expression was significantly higher in MSA (p= 0.002), in contrast to CD10 expression. CD15 positivity was significantly associated with microsatellite stable (MSS) tumors (p= 0.018). The association between CD10 positivity and fungating tumor growth showed marginal significance. Unlike CD10, CD15 positivity showed significant association with overall survival of colorectal MSA patients. CD15 expression seems to have a role in mucinous colorectal ACS, with significant impact on the survival of MSA patients. Further studies are suggested to identify any genetic alterations that may underlie a potential association with disease progression. [ABSTRACT FROM AUTHOR]

Background: It has been reported in oral squamous cell carcinoma (OSCC) that myeloid‐derived suppressor cells infiltrate tumor tissues. This study examined whether S‐1 chemotherapy changes immune cell populations in the tumor microenvironment. Methods: We examined 71 patients with of OSCC, including 51 patients who received preoperative S‐1 chemotherapy. Immunohistochemistry for PD‐L1, CD8, forkhead box protein 3 (FOXP3), and CD15 was performed using biopsy and resected specimens. Results: The numbers of CD8+, FOXP3+, and CD15+ cells in resected specimens were significantly decreased by S‐1 chemotherapy. The reduction of the proportion of CD15+ cells significantly differed between responders and nonresponders. Most responders were distributed into the group with low PD‐L1 expression and a low density of CD8+ cells before chemotherapy. Furthermore, many patients with recurrence exhibited a high density of CD15+ cells in biopsy specimens. Conclusion: Preoperative S‐1 chemotherapy can potentially improve prognosis by reducing CD15+ cells in the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Introduction: Acute funisitis, a granulocyte-related inflammation of the umbilical cord, is associated with chorioamnionitis and perinatal adverse events. However, there is no efficient procedure for detecting clinically relevant umbilical cord inflammation. The objective of this study was to identify such inflammation, based on immunohistochemical assessment of umbilical cord vasculitis patterns.Methods: Accordingly, 261 cases were retrieved from a single medical institute. Using the well-established granulocyte marker CD15, we developed a five-tier umbilical cord inflammation-scoring system. Additionally, previous morphological assessments from pathological reports were compared to the immunohistochemical findings.Results: Analysis of results based on our new scoring system revealed that severe umbilical phlebitis (score 3) was significantly associated with maternal inflammatory response and that severe umbilical arteriophlebitis (score 4) was correlated with low umbilical arterial blood pH, a feature linked to fetal mortality and morbidity. These results corresponded with and were validated by the morphology-based assessments. Additionally, immunohistochemical analysis revealed the clinical and pathological relevance of vitelline vasculitis, a recently proposed condition. We found that analyzing three umbilical cord sections enabled superior detection of severe umbilical vasculitis than analyzing two sections. However, whether these sections were sampled from multiple distant sites or a single localized site did not significantly affect the detection of clinically relevant inflammation.Discussion: CD15 immunohistochemistry is a potent tool for observing the patterns of clinically relevant umbilical vasculitis, especially in cases that were indeterminate according to morphology alone. Sampling three umbilical cord sections was an efficient procedure for addressing the spatial heterogeneity of umbilical cord inflammation. CD15 immunohistochemistry is a potent tool for observing the patterns of clinically relevant umbilical vasculitis, especially in cases that were indeterminate according to morphology alone. Sampling three umbilical cord sections was an efficient procedure for addressing the spatial heterogeneity of umbilical cord inflammation. [ABSTRACT FROM AUTHOR]

The outcome of patients with cutaneous melanoma has been strongly modified by recent advances obtained with Immune Checkpoint Inhibitors (ICIs). However, despite this breakthrough, durable response to ICIs is limited to a subset of patients. We investigated whether the expression of TRF2, which preserves telomere integrity, and have an effect on tumor immunosurveillance notably by directly recruiting and activating myeloid-derived suppressor cells (MDSCs), could be a prognostic biomarker in patients with relapsed or metastatic melanoma based on different treatment regimens. We evaluated retrospectively the association of TRF2 expressed in melanoma cells in combination with intratumoral CD33+ CD15+ CD14- MDSCs, as detected by immunohistochemistry and quantified by digital analysis, to clinicopathological features and overall survival (OS) among 48 patients treated with ICIs and 77 patients treated with other treatment options. The densities/mm2 of TRF2+ cells (P=.003) and CD33+ cells (P=.004) were individually significantly related to poor OS. In addition, only the combined expression of CD33+/CD15+/CD14- cells/mm2 was significantly correlated to poor OS (P=.017) in the whole study population as well as in patients treated by ICIs (P=.023). There was no significant difference in OS when analyzing the other markers individually or in combination according to the treatment regimen. The pre-treatment assessment of TRF2 expression and CD33+ cells/mm2 along with the density of CD33+/CD15+/CD14- cells/mm2 could assess OS and better predict clinical response of patients with melanoma treated by ICIs.

Introduction: Fetal hypoxic events with unclear predictive value are a common indication for placenta examination. We evaluated whether the use of CD15 immunostaining can improve the assessment of severity and duration of fetal hypoxia.Methods: We compared placentas (37-42 gestational weeks) from stillborns/newborns with birth asphyxia (BA) and non-hypoxic newborns. Placental findings were studied in following groups: (1) acute BA (n = 11) due to placental abruption, (2) non-acute BA (n = 121) due to non-acute conditions, (3) non-BA (n = 46) in pregnancies with preeclampsia and gestational diabetes, and (4) controls (n = 30).Results: A high expression of CD15 in feto-placental resistance vessels (FRVs) was present in non-acute BA (95.9%), but absent in acute BA, non-BA and controls (p < 0.0001). Furthermore, we found no causal relationship of high expression of CD15 in FRVs to coexisting placental conditions, including severity and mechanisms/patterns of placental injury, fetal erythroblastosis, and maternal conditions. According to a multivariate analysis, only a high expression of CD15 in FRVs was independently associated with severe non-acute fetal hypoxia ([OR] = 15.52; 95% [CI] = 5.92-40.67).Discussion: We have defined a characteristic pattern of CD15 expression in FRVs that allows to interpret various clinical/placental conditions with respect to fetal hypoxia, with an improved predictability compared to conventional analyses. This approach represents a novel diagnostic strategy for placenta examination, which could indirectly assess severity and duration of intrauterine hypoxia in a heterogeneous population of newborns. [ABSTRACT FROM AUTHOR]

The outcome of patients with cutaneous melanoma has been strongly modified by recent advances obtained with Immune Checkpoint Inhibitors (ICIs). However, despite this breakthrough, durable response to ICIs is limited to a subset of patients. We investigated whether the expression of TRF2, which preserves telomere integrity, and have an effect on tumor immunosurveillance notably by directly recruiting and activating myeloid-derived suppressor cells (MDSCs), could be a prognostic biomarker in patients with relapsed or metastatic melanoma based on different treatment regimens. We evaluated retrospectively the association of TRF2 expressed in melanoma cells in combination with intratumoral CD33+ CD15 + CD14- MDSCs, as detected by immunohistochemistry and quantified by digital analysis, to clinicopathological features and overall survival (OS) among 48 patients treated with ICIs and 77 patients treated with other treatment options. The densities/mm² of TRF2+ cells (P=.003) and CD33+ cells (P=.004) were individually significantly related to poor OS. In addition, only the combined expression of CD33+/CD15 +/CD14- cells/mm² was significantly correlated to poor OS (P=.017) in the whole study population as well as in patients treated by ICIs (P=.023). There was no significant difference in OS when analyzing the other markers individually or in combination according to the treatment regimen. The pre-treatment assessment of TRF2 expression and CD33+ cells/mm² along with the density of CD33+/CD15+/CD14- cells/mm² could assess OS and better predict clinical response of patients with melanoma treated by ICIs. [ABSTRACT FROM AUTHOR]

Background: Hodgkin’s lymphoma is one of the most commonly diagnosed lymphomas in Western society. Today Reed-Sternberg cells are identified by positive staining of several biomarkers. The IMP3 (insulin-like growth factor II m-RNA-binding protein 3) marker is a member of the insulin-like growth factor II mRNA binding protein family that has been suggested as a diagnostic marker in some epithelial malignancies. In this study, we aimed to evaluate the expression profile of IMP3 in Hodgkin’s lymphoma patients and compare it with those with large cell lymphoma. Methods: In this study, patients diagnosed with Hodgkin’s lymphoma between 2016 and 2018 were recruited. For the control group, patients diagnosed with large cell lymphoma were chosen. Paraffin blocks were collected and cut by a microtome machine. Immunohistochemical staining was performed on the slides for the IMP3 marker, using the Envision method. The color intensity was divided into four groups, and data on age, gender, staining intensity, sampling rate, and staining pattern entered at the end of the checklists. The collected data were analyzed using SPSS 19 software. The paired t-test has was employed, and a significant statistical level of 0.05 was considered in all tests. Results: In this study, 145 patients in a wide range of 5 to 84 years (the mean age = 41 ± 17 years) were studied. Fifty-three patients were diagnosed with diffuse large B-cell lymphoma (36.6%), 4 cases (2.8%) with anaplastic large cell lymphoma and 88 cases with (60.7%) Hodgkin’s lymphoma. Among 145 patients in the current study, 143 patients (98.6%) were positive for IMP3. IMP3 was positive in all patients with Hodgkin’s lymphoma and anaplastic large cell lymphoma, and only 2 cases of diffuse large B-cell lymphoma were negative for this maker, in whom severe necrosis was noted. Consequently, there is not a vivid difference between Hodgkin’s lymphoma and non-Hodgkin’s lymphoma (p-value=0.153) Conclusion: The marker is positive for Hodgkin’s lymphoma with a negative background and may be used as a supplementary marker along with CD15 and CD30 to detect neoplastic cells. However, it cannot help differentiate it from large cell lymphomas because it is also positive for non-Hodgkin lymphomas.

Oral ulcers constitute one of the most common chief complaints of patients attending any dental practice. The cause of oral mucosal ulceration is generally attributed to acute or chronic trauma from local factors. However, oral lesions may be the initial manifestation of many systemic conditions. Moreover, a group of oral ulcerative lesions have been reported to exhibit vast numbers of eosinophils and known as Traumatic Ulcerative Granuloma with Stromal Eosinophilia (TUGSE). We present two cases of oral ulcers which on microscopic examination exhibited numerous eosinophils from ulcerated epithelium to deep into the submucosa and an exuberant lymphoid proliferation. CD15 immunohistochemical marker was used in these cases to ease the identification of the eosinophils. We also highlight the differential diagnosis of TUGSE that may manifest as oral lesions, as an important diagnostic guide for clinicians in contemporary practice. [ABSTRACT FROM AUTHOR]

Background: Hodgkin's lymphoma is one of the most commonly diagnosed lymphomas in Western society. Today Reed-Sternberg cells are identified by positive staining of several biomarkers. The IMP3 (insulin-like growth factor II m-RNA-binding protein 3) marker is a member of the insulin-like growth factor II mRNA binding protein family that has been suggested as a diagnostic marker in some epithelial malignancies. In this study, we aimed to evaluate the expression profile of IMP3 in Hodgkin's lymphoma patients and compare it with those with large cell lymphoma. Methods: In this study, patients diagnosed with Hodgkin's lymphoma between 2016 and 2018 were recruited. For the control group, patients diagnosed with large cell lymphoma were chosen. Paraffin blocks were collected and cut by a microtome machine. Immunohistochemical staining was performed on the slides for the IMP3 marker, using the Envision method. The color intensity was divided into four groups, and data on age, gender, staining intensity, sampling rate, and staining pattern entered at the end of the checklists. The collected data were analyzed using SPSS 19 software. The paired t-test has was employed, and a significant statistical level of 0.05 was considered in all tests. Results: In this study, 145 patients in a wide range of 5 to 84 years (the mean age = 41 ± 17 years) were studied. Fifty-three patients were diagnosed with diffuse large B-cell lymphoma (36.6%), 4 cases (2.8%) with anaplastic large cell lymphoma and 88 cases with (60.7%) Hodgkin's lymphoma. Among 145 patients in the current study, 143 patients (98.6%) were positive for IMP3. IMP3 was positive in all patients with Hodgkin's lymphoma and anaplastic large cell lymphoma, and only 2 cases of diffuse large B-cell lymphoma were negative for this maker, in whom severe necrosis was noted. Consequently, there is not a vivid difference between Hodgkin's lymphoma and non-Hodgkin's lymphoma (p-value=0.153). Conclusion: The marker is positive for Hodgkin's lymphoma with a negative background and may be used as a supplementary marker along with CD15 and CD30 to detect neoplastic cells. However, it cannot help differentiate it from large cell lymphomas because it is also positive for non-Hodgkin lymphomas. [ABSTRACT FROM AUTHOR]

Cancer stem cell (CSC) markers have prognostic significance in various cancers, but their clinical significance in papillary thyroid carcinoma (PTC) has not been demonstrated. In this study, CSC markers expressed in PTC and their relationships with prognosis were evaluated. We constructed tissue microarrays for 386 PTC cases, divided it into 42 low risk cases and 344 intermediate risk cases according to the American Thyroid Association 2009 Risk Stratification System. Immunohistochemical staining of CSC markers (CD15, CD24, CD44, CD166, and ALDH1A1) was performed, and the proportion of stained cells and immunostaining intensity were evaluated to determine positive marker expression. The relationships between CSC marker expression and other clinicopathological parameters or survival were analyzed. CD15 expression was higher in PTC with intermediate risk than in PTC with low risk (29.4 vs. 11.9%, p = 0.017). According to a multivariate analysis, CD15, CD44, CD166, and ALDH1A1 positivity were independently associated with a shorter progression-free survival (PFS) (odds ratio [OR]: 1.929, 2.960, 7.485, and 3.736; p = 0.016, p = 0.026, p < 0.001, and p = 0.006, respectively). Higher N and cancer stage were the only other clinical factors associated with a shorter PFS (OR: 2.953 and 1.898, p = 0.011 and p = 0.034). Overexpression of CSC markers in PTC was associated with shorter PFS during follow-up. Immunohistochemical staining of CSC markers may provide useful information for predicting patient outcomes.

Introduction: Tumor cells use adhesion molecules like CD15 or sialylCD15 (sCD15) for metastatic spreading. We analyzed the expression of CD15 and sCD15 in clear cell renal cell carcinoma (ccRCC) regarding prognosis., Methods: A tissue microarray containing tissue specimens of 763 patients with ccRCC was immunohistochemically stained for CD15 and sCD15, their expression quantified using digital image analysis, and the impact on patients' survival analyzed. The cell lines 769p and 786o were stimulated with CD15 or control antibody in vitro and the effects on pathways activating AP-1 and tumor cell migration were examined., Results: ccRCC showed a broad range of CD15 and sCD15 expression. A high CD15 expression was significantly associated with favorable outcome (p &lt; 0.01) and low-grade tumor differentiation (p &lt; 0.001), whereas sCD15 had no significant prognostic value. Tumors with synchronous distant metastasis had a significantly lower CD15 expression compared to tumors without any (p &lt; 0.001) or with metachronous metastasis (p &lt; 0.01). Tumor cell migration was significantly reduced after CD15 stimulation in vitro, but there were no major effects on the activating pathways of AP-1., Conclusion: CD15, but not sCD15, qualifies as a biomarker for risk stratification and as an interesting novel target in ccRCC. Moreover, the data indicate a contribution of CD15 to metachronous metastasis. Further research is warranted to decipher the intracellular pathways of CD15 signaling in ccRCC in order to characterize the CD15 effects on ccRCC more precisely., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Cancer stem cell (CSC) markers have prognostic significance in various cancers, but their clinical significance in papillary thyroid carcinoma (PTC) has not been demonstrated. In this study, CSC markers expressed in PTC and their relationships with prognosis were evaluated. We constructed tissue microarrays for 386 PTC cases, divided it into 42 low risk cases and 344 intermediate risk cases according to the American Thyroid Association 2009 Risk Stratification System. Immunohistochemical staining of CSC markers (CD15, CD24, CD44, CD166, and ALDH1A1) was performed, and the proportion of stained cells and immunostaining intensity were evaluated to determine positive marker expression. The relationships between CSC marker expression and other clinicopathological parameters or survival were analyzed. CD15 expression was higher in PTC with intermediate risk than in PTC with low risk (29.4 vs. 11.9%, p = 0.017). According to a multivariate analysis, CD15, CD44, CD166, and ALDH1A1 positivity were independently associated with a shorter progression-free survival (PFS) (odds ratio [OR]: 1.929, 2.960, 7.485, and 3.736; p = 0.016, p = 0.026, p < 0.001, and p = 0.006, respectively). Higher N and cancer stage were the only other clinical factors associated with a shorter PFS (OR: 2.953 and 1.898, p = 0.011 and p = 0.034). Overexpression of CSC markers in PTC was associated with shorter PFS during follow-up. Immunohistochemical staining of CSC markers may provide useful information for predicting patient outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Metastatic non-small cell lung (NSCLC) cancer represents one of the most common types of brain metastasis. The mechanisms involved in how circulating cancer cells transmigrate into brain parenchyma are not fully understood. The aim of this work was to investigate the role of fucosylated carbohydrate epitopes CD15 and sialyated CD15s in cancer adhesion to brain-derived endothelial cells and determine their influence in blood–brain barrier (BBB) disruption Methods: Three distinct, independent methods were used to measure brain endothelial integrity and include voltohmmeter (EVOM™), impedance spectroscopy (CellZscope®) and electric cell-substrate impedance sensing system (ECIS™). Two fucosyltransferases (FUT4 and 7) responsible for CD15 and CD15s synthesis were modulated in four human cancer cell lines (three lung cancer and one glioma). Results: Overexpression of CD15 or CD15s epitopes led to increase in adhesion of cancer cells to cerebral endothelial cells compared with wild-type and cells with silenced CD15 or CD15s (p < 0.01). This overexpression led to the disruption of cerebral endothelial cell monolayers (p < 0.01). Knockdown of FUT4 and FUT7 in metastatic cancer cells prevented disruption of an in vitro BBB model. Surprisingly, although the cells characterised as 'non-metastatic', they became 'metastatic' -like when cells were forced to over-express either FUT4 or FUT7. Conclusions: Results from these studies suggest that overexpression of CD15 and CD15s could potentiate the transmigration of circulating NSCLC cells into the brain. The clinical significance of these studies includes the possible use of these epitopes as biomarkers for metastasis. [ABSTRACT FROM AUTHOR]

The diagnosis of classic Hodgkin lymphoma requires immunohistochemical confirmation in most cases and one can argue for these studies as standard-of-care in the diagnostic workup. The authors propose a panel of studies for primary identification of CHL to include: CD3, CD20, CD15, CD30 and PAX5. When pattern discordances are identified, additional assessment is recommended. In the case of overexpression of B lineage markers by Hodgkin/Reed-Sternberg cells, or a differential diagnosis that includes large B-cell lymphoma or variants, additional markers recommended are: CD45, OCT2, BOB1, CD79a and MUM1/IRF4. If primary mediastinal large B cell lymphoma is considered in the differential diagnosis, suggested additional markers include: P63, CD23, CD45 and CD79a. When considering a differential diagnosis that includes anaplastic large cell lymphoma we suggest: ALK, CD45, pan T cell antigens (such as CD2, CD5, CD7, and CD43), and cytotoxic markers (granzyme, perforin, and TIA1). If peripheral T cell lymphoma or T cell lymphomas of follicular helper origin are considered in the differential diagnosis, the following panel is recommended: pan T cell antigens, CD4, CD8, one or more follicular dendritic cell markers, and assessment for Epstein-Barr virus (EBV) infection, preferably EBV encoded RNA (EBER) as assessed by in situ hybridization When the differential diagnosis includes nodular lymphocyte predominant Hodgkin lymphoma, recommended additional studies include OCT2, CD21 and/or CD23, PD1, and assessment for EBV infection. The authors recognize that these panels may not be adequate to completely characterize other lymphomas, but these panels will usually be sufficient to distinguish classic Hodgkin lymphoma from other lymphoma types. [ABSTRACT FROM AUTHOR]

Objectives: To investigate mechanisms of in utero death in normally formed fetuses by measuring amniotic fluid (AF) biomarkers for hypoxia (erythropoietin [EPO]), myocardial damage (cardiac troponin I [cTnI]) and brain injury (glial fibrillary acidic protein [GFAP]), correlated with risk factors for fetal death and placental histopathology. Methods: This retrospective, observational cohort study included intrauterine deaths with transabdominal amniocentesis prior to induction of labor. Women with a normal pregnancy and an indicated amniocentesis at term were randomly selected as controls. AF was assayed for EPO, cTnI and GFAP using commercial immunoassays. Placental histopathology was reviewed, and CD15-immunohistochemistry was used. Analyte concentrations >90th centile for controls were considered "raised". Raised AF EPO, AF cTnI and AF GFAP concentrations were considered evidence of hypoxia, myocardial and brain injury, respectively. Results: There were 60 cases and 60 controls. Hypoxia was present in 88% (53/60), myocardial damage in 70% (42/60) and brain injury in 45% (27/60) of fetal deaths. Hypoxic fetuses had evidence of myocardial injury, brain injury or both in 77% (41/53), 49% (26/53) and 13% (7/53) of cases, respectively. Histopathological evidence for placental dysfunction was found in 74% (43/58) of these cases. Conclusion: Hypoxia, secondary to placental dysfunction, was found to be the mechanism of death in the majority of fetal deaths among structurally normal fetuses. Ninety-one percent of hypoxic fetal deaths sustained brain, myocardial or both brain and myocardial injuries in utero. Hypoxic myocardial injury was an attributable mechanism of death in 70% of the cases. Non-hypoxic cases may be caused by cardiac arrhythmia secondary to a cardiac conduction defect. [ABSTRACT FROM AUTHOR]

Sphere formation is an indicator of tumor aggressiveness independent of the tumor grade; however, its relation to progression‐free survival (PFS) is less known. This study was designed to assess the neurosphere forming ability among low grade glioma (LGG) and high‐grade glioma (HGG), its stem cell marker expression, and correlation to PFS. Tumor samples of 140 patients, including (LGG; n = 67) and (HGG; n = 73) were analyzed. We used sphere forming assay, immunofluorescence, and immunohistochemistry to characterize the tumors. Our study shows that, irrespective of the pathological sub type, both LGG and HGG formed neurospheres in vitro under conventional sphere forming conditions. However, the number of neurospheres formed from tumor tissues were significantly higher in HGG compared to LGG (P < 0.0001). Different grades of glioma were further characterized for the expression of stem cell marker proteins and lineage markers. When neurospheres were analyzed, CD133 positive cells were identified in addition to CD15 and nestin positive cells in both LGG and HGG. When these neurospheres were subjected to differentiation, cells positive for GFAP and β‐tubulin III were observed. Expression of stem cell markers and β‐tubulin III were prominent in HGG compared to LGG, whereas GFAP expression was higher in LGG than in HGG. Kaplan–Meier survival analysis demonstrated that neurosphere forming ability was significantly associated with shorter PFS (P < 0.05) in both LGG and HGG. Our results supports earlier studies that neurosphere formation may serve as a definitive indicator of stem cell population within the tumor and thus a better predictor of PFS than the tumor grades alone. © 2018 IUBMB Life, 71(1):244–253, 2019 [ABSTRACT FROM AUTHOR]

The prognostic role of CD15 in acute myeloid leukemia (AML) has been tested in different studies with conflicting results. To address this issue, we retrospectively evaluated a cohort of 460 AML patients of all ages with the exclusion of acute promyelocytic leukemia (M/F 243/217, median age 50.6 years [range 0.9-81.2]) intensively treated at our institute between January 1999 and December 2010. CD15 positivity was found in 171 of 406 evaluable patients (42.1%). Complete remission (CR) was achieved by 334 patients (72.6%), while 82 (17.8%) were resistant and 44 (9.6%) died during induction: the median CR duration was 15.5 months (range 0.6-176.0), with 2-year disease-free survival rate of 45.1% (95% confidence interval 39.6-50.6). The median overall survival was 14.4 months (range 0.3-177.0), with 2-year overall survival rate of 42.2% (95% confidence interval 37.5-46.9). At univariate analysis for CR achievement, age < 60 years (P < .001), World Health Organization classification (P = .045), low-risk karyotype (P < .001), no high-risk karyotype (P = .006), positivity for AML-ETO (P = .004)/CBFβ-MYH11 (P = .003)/CD15 (P = .006)/CD11b (P = .013), negativity for FLT3-ITD (P = .001), Hb > 8 g/dL (P = .020), and white blood cell < 50 × 109 /L (P = .034) had a favorable impact. At a multivariate logistic regression model, CD15 positivity (P = .002), age < 60 years (P = .008), white blood cell < 50 × 109 /L (P = .017), and low-risk/no high-risk karyotype (P = .026/P = .025) retained an independent prognostic role on CR achievement. The baseline assessment of CD15 positivity appears to have a role in the risk evaluation for CR achievement in AML patients undergoing intensive chemotherapy and should be assessed in prospective studies together with other clinical and biologic features already reported. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]