Ethyl cellulose/gelatin/ß-cyclodextrin/curcumin nanofibrous membrane with antibacterial and formaldehyde adsorbable capabilities for lightweight and high-performance air filtration.

Functionalization of bio-based nanofibers is the development tendency of high-performance air filter. However, the conventional structural optimization strategy based on high solution conductivity greatly hinders the development of fully bio-based air filter, and not conducive to sustainable development. This work fabricated fully bio-based nanofibrous membrane with formaldehyde-adsorbable and antibacterial capabilities by electrospinning low-conductivity solution for high-performance air filtration and applied to lightweight mask. The "water-like" ethyl cellulose (EC) was selected as the base polymer to "nourish" functional materials of gelatin (GE), ß-cyclodextrin (ßCD), and curcumin (Cur), thus forming a solution system with high binding energy differences and electrospinning into ultrafine bimodal nanofibers. The filtration efficiency for 0.3 µm NaCl particles, pressure drop, and quality factor were 99.25 %, 53 Pa, and 0.092 Pa-1, respectively; the bacteriostatic rates against Escherichia coli and Staphylococcus aureus were 99.9 % and 99.4 %, respectively; the formaldehyde adsorption capacity was 442 µg/g. This is the first report on antibacterial and formaldehyde-adsorbable high-performance air filter entirely made from bio-based materials. This simple strategy will greatly broaden the selection of materials for preparing high-performance multifunctional air filter, and promote the development of bio-based air filter.

Cholinergic neurons trigger epithelial Ca2+ currents to heal the gut.

A fundamental and unresolved question in regenerative biology is how tissues return to homeostasis after injury. Answering this question is essential for understanding the aetiology of chronic disorders such as inflammatory bowel diseases and cancer1. We used the Drosophila midgut2 to investigate this and discovered that during regeneration a subpopulation of cholinergic3 neurons triggers Ca2+ currents among intestinal epithelial cells, the enterocytes, to promote return to homeostasis. We found that downregulation of the conserved cholinergic enzyme acetylcholinesterase4 in the gut epithelium enables acetylcholine from specific Egr5 (TNF in mammals)-sensing cholinergic neurons to activate nicotinic receptors in innervated enterocytes. This activation triggers high Ca2+, which spreads in the epithelium through Innexin2-Innexin7 gap junctions6, promoting enterocyte maturation followed by reduction of proliferation and inflammation. Disrupting this process causes chronic injury consisting of ion imbalance, Yki (YAP in humans) activation7, cell death and increase of inflammatory cytokines reminiscent of inflammatory bowel diseases8. Altogether, the conserved cholinergic pathway facilitates epithelial Ca2+ currents that heal the intestinal epithelium. Our findings demonstrate nerve- and bioelectric9-dependent intestinal regeneration and advance our current understanding of how a tissue returns to homeostasis after injury.

Epithelial Ca2+ waves triggered by enteric neurons heal the gut.

A fundamental and unresolved question in regenerative biology is how tissues return to homeostasis after injury. Answering this question is essential for understanding the etiology of chronic disorders such as inflammatory bowel diseases and cancer. We used the Drosophila midgut to investigate this question and discovered that during regeneration a subpopulation of cholinergic enteric neurons triggers Ca2+ currents among enterocytes to promote return of the epithelium to homeostasis. Specifically, we found that down-regulation of the cholinergic enzyme Acetylcholinesterase in the epithelium enables acetylcholine from defined enteric neurons, referred as ARCENs, to activate nicotinic receptors in enterocytes found near ARCEN-innervations. This activation triggers high Ca2+ influx that spreads in the epithelium through Inx2/Inx7 gap junctions promoting enterocyte maturation followed by reduction of proliferation and inflammation. Disrupting this process causes chronic injury consisting of ion imbalance, Yki activation and increase of inflammatory cytokines together with hyperplasia, reminiscent of inflammatory bowel diseases. Altogether, we found that during gut regeneration the conserved cholinergic pathway facilitates epithelial Ca2+ waves that heal the intestinal epithelium. Our findings demonstrate nerve- and bioelectric-dependent intestinal regeneration which advance the current understanding of how a tissue returns to its homeostatic state after injury and could ultimately help existing therapeutics.

Tumor Cytokine-Induced Hepatic Gluconeogenesis Contributes to Cancer Cachexia: Insights from Full Body Single Nuclei Sequencing.

A primary cause of death in cancer patients is cachexia, a wasting syndrome attributed to tumor-induced metabolic dysregulation. Despite the major impact of cachexia on the treatment, quality of life, and survival of cancer patients, relatively little is known about the underlying pathogenic mechanisms. Hyperglycemia detected in glucose tolerance test is one of the earliest metabolic abnormalities observed in cancer patients; however, the pathogenesis by which tumors influence blood sugar levels remains poorly understood. Here, utilizing a Drosophila model, we demonstrate that the tumor secreted interleukin-like cytokine Upd3 induces fat body expression of Pepck1 and Pdk, two key regulatory enzymes of gluconeogenesis, contributing to hyperglycemia. Our data further indicate a conserved regulation of these genes by IL-6/JAK-STAT signaling in mouse models. Importantly, in both fly and mouse cancer cachexia models, elevated gluconeogenesis gene levels are associated with poor prognosis. Altogether, our study uncovers a conserved role of Upd3/IL-6/JAK-STAT signaling in inducing tumor-associated hyperglycemia, which provides insights into the pathogenesis of IL-6 signaling in cancer cachexia.

2-Methoxyestradiol inhibits the proliferation level in keloid fibroblasts through p38 in the MAPK/Erk signaling pathway.

BACKGROUND: The MAPK/Erk signaling pathway is a classic pathway in cell proliferation. Our former study showed that keloid tissue revealed a higher proliferation level than physiological scars and normal skin. As a natural metabolite of estradiol, 2-methoxyestradiol (2ME2) showed an inhibition proliferation effect on tumor cells. AIM: In this study, the treatment effect of 2ME2 and its potential mechanisms are explored. METHODS: Six keloid patients and six non-keloid patients were randomly selected from the Department of Plastic Surgery at our hospital during June 2021 to December 2021. Six groups were established: normal skin fibroblasts (N); keloid fibroblasts (K); keloid fibroblasts treated with 2ME2 (K + 2ME2); keloid fibroblasts treated with dimethyl sulfoxide (DMSO) (K + DMSO); keloid fibroblasts treated with doramapimod (K + IN); keloid fibroblasts treated with doramapimod (p38 inhibitor) and 2ME2 (K + IN+2ME2). The fibroblast activity and key factor expression of the MAPK/Erk signaling pathway were measured. RESULTS: In the results, 2ME2 significantly inhibited keloid fibroblast activity and key factor expression (except STAT1). CONCLUSION: The proliferation levels were reduced by both the p38 inhibitor and 2ME2, indicating 2ME2 may achieve an antiproliferation effect by targeting p38 in keloid fibroblasts.

Dietary Folate Deficiency Promotes Lactate Metabolic Disorders to Sensitize Lung Cancer Metastasis through MTOR-Signaling-Mediated Druggable Oncotargets.

Lactate metabolism plays a pivotal role in cancers but is often overlooked in lung cancer (LC). Folate deficiency has been linked to lung cancer development, but its impact on lactate metabolism and cancer malignancy is unclear. To investigate this, mice were fed either a folate-deficient (FD) or control diet and intrapleurally implanted with lung cancer cells pre-exposed to FD growth medium. Results showed that FD promoted lactate over-production and the formation of tumor oncospheroids (LCSs) with increased metastatic, migration, and invasion potential. Mice implanted with these cells and fed an FD diet developed hyperlactatemia in blood and lungs. This coincided with increased expression of hexokinase 2 (HK2), lactate dehydrogenase (LDH), and decreased expression of pyruvate dehydrogenase (PDH). Pre-treatment of the FD-LCS-implanted mice with the mTORC1 inhibitor, rapamycin, and the anti-metabolic drug metformin abolished FD/LCS-activated mTORC1 and its targets including HIF1α, HK2, LDH, and monocarboxylate transporters (MCT1 and MCT4), which coincided with the reduction in lactate disorders and prevention of LC metastasis. The findings suggest that dietary FD promotes lactate metabolic disorders that sensitize lung cancer metastasis through mTOR-signaling-mediated targets.

Identification of a stem cell mediating osteoblast versus adipocyte lineage selection.

Most skeletal fragility disorders are characterized by bone loss with a concurrent gain in marrow adipocytes 1-8. This suggests that a cell that forms adipocytes at the expense of osteoblasts is central to the pathogenesis of skeletal disorders. However, this cellular point of bifurcation between adipocyte and osteoblast differentiation pathways remains unknown. Here, we identify a new cell type defined by co-expression of skeletal stem cell and adipocyte precursor markers, 9-13 (CD24+CD29+ skeletal stem cells (SSCs)), that serves as a key cellular point of bifurcation between the osteoblast and adipocyte differentiation pathways, giving rise to closely related osteoblast and adipocyte lineage-restricted precursors. CD24+CD29+SSCs comprise a small fraction of SSCs, and only this fraction displays full stemness features, including the ability to undergo serial transplantation. In line with serving as the osteoblast/adipocyte bipotent cell, the "bone to fat" tissue remodeling occurring in models of postmenopausal osteoporosis or after high fat diet exposure occur in part by reprogramming these CD24+CD29+SSCs to change their output of lineage-restricted precursors. Lastly, as subcutaneous white adipose tissue displays a similar set of CD24+CD29+ stem cells and related lineage-restricted progenitors, these findings provide a new schema explaining the stem cell basis of bone versus adipose tissue production that unifies multiple mesenchymal tissues.

A comparison of proliferation levels in normal skin, physiological scar and keloid tissue.

Proliferation is an important characteristic of life, and many signaling pathways participate in this complicated process. The MAPK/Erk pathway is a classic pathway in cell proliferation. In this study, expression levels of key factors in the MAPK/Erk pathway were measured to assess the proliferation level among normal skin, physiological scar, and keloid tissue. Thirty patients were selected randomly from the Department of Plastic Surgery at Peking Union Medical College Hospital from January 2019 to December 2020. Histological appearance and fiber tissue content were observed by Hematoxylin and eosin staining and Masson staining. Expression levels of key factors in the MAPK/Erk pathway (ATF2, c-Jun, c-Myc, p38 and STAT1) and relative proteins (HIF-1α and PCNA) in tissues were detected by immunohistochemistry and analyzed as the percentage of positively stained cells in both the tissue epidermis and dermis. Western blot was used for quantitative analysis of the above factors. In results, keloid tissue showed a significantly higher fiber and less cell content. In the immunohistochemical result, higher expression of key factors was observed in the epidermis than in the dermal layer, and the expression of all factors was increased remarkably in keloid tissue. In western blot analysis, all factors (except STAT1) showed higher expression in keloid tissue. In our former research, keloid showed similar apoptosis level as physiological scar and normal skin. On combining our former conclusion and results in this study, an imbalance condition between the high proliferation level and normal apoptosis level may lead to the growth characteristics of keloid.

A new photodynamic therapy photosensitizer (p1) promotes apoptosis of keloid fibroblasts by targeting caspase-8.

Photodynamic therapy (PDT) is a new therapy for treating cancer with less toxicity, high selectivity, good cooperativity, and repetitive usability. However, keloid treatment by PDT is mainly focused on clinical appearance, and few studies have been conducted on the mechanisms of PDT. In this study, key factors of the classical mitochondrial apoptosis signaling pathway were measured to assess the effect of a new PDT photosensitizer (p1). A specific inhibitor of caspase-8 (Z-IETD-FMK) was also used to verify the possible mechanisms. Twelve samples were obtained from 12 patients (six with keloids and six without) selected randomly from the Department of Plastic Surgery at Peking Union Medical College Hospital from January to December 2020. After cell culture, fibroblasts were divided into 13 groups. The morphology of fibroblasts in each group was observed by microscopy. Cell activity was measured by cell counting kit-8, and cell apoptotic morphology was observed by TUNEL staining. The reactive oxygen species (ROS) relative value was measured by a ROS test kit. The expression levels of key mitochondrial factors (caspase-3, caspase-8, cytochrome-c, Bax, and Bcl-2) were assessed by western blot, and mRNA expression of caspase-3 and caspase-8 was measured by RT-qPCR. We showed that p1 had a satisfactory proapoptotic effect on keloid fibroblasts by increasing the expression of ROS, caspase-3, caspase-8, and cytochrome-c, and decreasing the Bcl-2/Bax ratio; however, this effect was partially inhibited by Z-IETD-FMK, indicating that caspase-8 may be one of the p1's targets to achieve the proapoptotic effect.

Suboptimal folic acid exposure rewires oncogenic metabolism and proteomics signatures to mediate human breast cancer malignancy.

Whether treatment with folic acid (FA) affects human breast cancer positively or negatively remains unclear. We subjected human Michigan Cancer Foundation-7 cells, a human breast cancer cell line, to suboptimal FA at low levels (10 nM; LF) and high levels (50 µM; HF) and investigated the molecular mechanisms underlying their effects through metabolic flux and systematic proteomics analyses. The data indicated that LF induced and HF aggravated 2-fold higher mitochondrial toxicity in terms of suppressed oxidative respiration, increased fermented glycolysis, and enhanced anchorage-independent oncospheroid formation. Quantitative proteomics and Gene Ontology enrichment analysis were used to profile LF- and HF-altered proteins involved in metabolism, apoptosis, and malignancy pathways. Through STRING analysis, we identified a connection network between LF- and HF-altered proteins with mammalian target of rapamycin (mTOR). Rapamycin-induced blockage of mTOR complex 1 (mTORC1) signaling, which regulates metabolism, differentially inhibited LF- and HF-modulated protein signatures of mitochondrial NADH dehydrogenase ubiquinone flavoprotein 2, mitochondrial glutathione peroxidase 4, kynureninase, and alpha-crystallin B chain as well as programmed cell death 5 in transcript levels; it subsequently diminished apoptosis and oncospheroid formation in LF/HF-exposed cells. Taken together, our data indicate that suboptimal FA treatment rewired oncogenic metabolism and mTORC1-mediated proteomics signatures to promote breast cancer development.

The potential biological effects of quercetin based on pharmacokinetics and multi-targeted mechanism in vivo.

Quercetin is a plant-derived polyphenol flavonoid that has been proven to be effective for many diseases. However, the mechanism and in vivo metabolism of quercetin remains to be clarified. It achieves a wide range of biological effects through various metabolites, gut microbiota and its metabolites, systemic mediators produced by inflammation and oxidation, as well as by multiple mechanisms. The all-round disease treatment of quercetin is achieved through the organic combination of multiple channels. Therefore, this article clarifies the metabolic process of quercetin in the body, and explores the new pattern of action of quercetin in the treatment of diseases.

Merkel cell carcinoma in the setting of hematologic disease is associated with unique features and potential pitfalls.

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine carcinoma of the skin, often associated with polyomavirus and ultra-violet light exposure. Immunosuppression is associated with increased risk of development of MCC, including that associated with hematolymphoid disorders such as chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We sought to determine whether MCC arising in patients with hematologic disorders showed unique features. Searching archived material at three institutions, we identified 13 patients with MCC and at least one hematologic malignancy and 41 patients with MCC with no reported hematologic malignancy. CLL/SLL was the most common hematologic disorder in this setting (9/13 cases). Clinical history, variation in morphologic appearance, unusual site distribution and concern for progression of underlying hematologic disease all contributed to potential diagnostic challenges. Overlapping marker expression between MCC and hematologic neoplasms created potential diagnostic pitfalls (e.g. CD138, Pax5, TdT, Bcl2, CD56, and CD117). In addition, we newly identify expression of CD5 and LEF-1 in a subset of MCC, including in patients with CLL/SLL. MCC in patients with hematologic malignancy were more common in men (92% versus 59%, p < 0.05) and showed an unusual site predilection to non-sun exposed sites (3/13 on the buttocks) with none presenting on the face or scalp. By contrast, face or scalp lesions were common in MCC without an associated hematologic malignancy (17/41, p < 0.05). Our findings reaffirm the need for skin surveillance in the setting of immune deficiency and for vigilance to identify unusual presentations of MCC in patients with or without hematologic disorders.

Plant-Based, Antioxidant-Rich Snacks Elevate Plasma Antioxidant Ability and Alter Gut Bacterial Composition in Older Adults.

Plant-rich diets alleviate oxidative stress and gut dysbiosis and are negatively linked to age-associated chronic disorders. This study examined the effects of consuming plant-based, antioxidant-rich smoothies and sesame seed snacks (PBASS) on antioxidant ability and gut microbial composition in older adults. Healthy and sub-healthy older adults (n = 42, 79.7 ± 8.6 years old) in two senior living facilities were given PBASS for 4 months. Blood and fecal samples were collected from these individuals at the baseline and after 2 and 4 months of PBASS consumption. After 2 months, serum levels of albumin and high-density lipoprotein-cholesterol and the ratio of reduced to oxidized glutathione (GSH/GSSG) had increased significantly and erythrocytic glutathione, GSH/GSSG and superoxide dismutase activity had decreased significantly compared with baseline levels (p < 0.05). After 4 months, red blood cells, hematocrit, serum blood urea nitrogen and erythrocyte glutathione peroxidase activity had decreased significantly, whereas plasma and erythrocyte protein-bound sulfhydryl groups had increased significantly. Furthermore, plasma glutathione and total antioxidant capacity were significantly greater after 2 months and increased further after 4 months of PBASS consumption. The results of next generation sequencing showed that PBASS consumption prompted significant decreases in observed bacterial species, their richness, and the abundance of Actinobacteria and Patescibacteria and increases in Bacteroidetes in feces. Our results suggest that texture-modified, plant-based snacks are useful nutrition support to benefit healthy ageing via the elevation of antioxidant ability and alteration of gut microbiota.

Identification of Latent Diagnostic Biomarkers and Biological Pathways in Dermatomyositis Based on WGCNA.

INTRODUCTION: Dermatomyositis (DM) is a chronic autoimmune disease of predominantly lymphocytic infiltration mainly involving the transverse muscle. Its pathogenesis is remaining unknown. This research is designed to probe the latent pathogenesis of dermatomyositis, identify potential biomarkers, and reveal the pathogenesis of dermatomyositis through information biology analysis of gene chips. METHODS: In this study, we utilised the GSE14287 and GSE11971 datasets rooted in the Gene Expression Omnibus (GEO) databank, which included a total of 62 DM samples and 9 normal samples. The datasets were combined, and the differentially expressed gene sets were subjected to weighted gene coexpression network analysis, and the hub gene was screened using a protein interaction network from genes in modules highly correlated with dermatomyositis progression. RESULTS: A total of 3 key genes-myxovirus resistance-2 (MX2), oligoadenylate synthetase 1 (OAS1), and oligoadenylate synthetase 2 (OAS2)-were identified in combination with cell line samples, and the expressions of the 3 genes were verified separately. The results showed that MX2, OAS1, and OAS2 were highly expressed in LPS-treated cell lines compared to normal cell lines. The results of pathway enrichment analysis of the genes indicated that all 3 genes were enriched in the cytosolic DNA signalling and cytokine and cytokine receptor interaction signalling pathways; the results of functional enrichment analysis showed that all 3 were enriched in interferon-α response and interferon-γ response functions. CONCLUSIONS: This is important for the study of the pathogenesis and objective treatment of dermatomyositis and provides important reference information for the targeted therapy of dermatomyositis.

Resveratrol inhibits proliferation and promotes apoptosis of keloid fibroblasts by targeting HIF-1α.

A keloid is characterized by red, tickling, hard, and irregular raised tissues, and it tends to outgrow its origin. It frequently occurs in young adults and appears to be refractory to prevailing therapies. Resveratrol is a new drug that has anti-proliferative effect. In this study, keloid-derived fibroblasts were cultured under hypoxia environment and was treated by resveratrol. CCK-8 assay and Annexin V-FITC were used to evaluate cell activity and apoptosis level. Western blot and RT-qPCR were also used to assess the expression of HIF-α, Collagen I and Collagen III. Besides, siRNA was also used to explore the mechanisms of resveratrol's effect. In this study, hypoxia promotes proliferation and inhibits apoptosis of keloid fibroblasts. These findings highlight the potential obstacle in treating keloids. Furthermore, we demonstrated that resveratrol could reverse the effect of hypoxia on keloids through down-regulation of HIF-1α. Moreover, collagen synthesis in keloid fibroblasts was also inhibited by resveratrol, which corresponded with HIF-1α suppression. These results provide evidence for resveratrol's treatment effect against keloids through inhibiting cell proliferation and promoting cell apoptosis, while, HIF-1α may play the key role in this process.

Hyperbaric oxygen therapy relieved pruritus and pain of keloid patients.

Objective: Keloid patients usually have local pruritus and pain. In our clinical work, we have found keloid patients after receiving hyperbaric oxygen (HBO) therapy reflect less pruritus and pain. The hypothesis was that patients with keloid and a history of HBO therapy would have less pruritus and pain than patients without HBO therapy, and the pruritus or pain-related factors were detected in keloid with/without HBO therapy and normal skin. Methods: Three groups of samples were established: keloid samples from patients with HBO therapy for two weeks before and after surgery (H group); keloid samples from patients without HBO therapy (G group); normal skin samples from patients without obvious scar (N group). Hematoxylin and eosin (H&E) staining was used to observe morphological changes. Pruritus/pain related factors: Tryptophan Hydroxylase1 (TPH1), connexin-43 (Cx43) and transient receptor potential vanilloid type 1 (TRPV1) were detected by immunofluorescence and western blot technology. The expression of these factors' mRNA was also measured by the real-time quantitative polymerase chain reaction (RT-qPCR). Results: Among three groups, G group presented significantly highest expression levels of TPH1, Cx43 and TRPV1, conversely, N group presented significantly lowest expression levels of TPH1, Cx43 and TRPV1. Conclusion: TPH1, Cx43 and TRPV1 were overexpressed in the samples of keloid patients, indicating that the pruritus and pain of keloid might be related to these factors. Furthermore, TPH1, Cx43 and TRPV1 were expressed highest in keloid patients without HBO therapy, indicating that HBO therapy might relief pruritus of keloid patients by regulating these factors.

A cell atlas of the adult Drosophila midgut.

Studies of the adult Drosophila midgut have led to many insights in our understanding of cell-type diversity, stem cell regeneration, tissue homeostasis, and cell fate decision. Advances in single-cell RNA sequencing provide opportunities to identify new cell types and molecular features. We used single-cell RNA sequencing to characterize the transcriptome of midgut epithelial cells and identified 22 distinct clusters representing intestinal stem cells, enteroblasts, enteroendocrine cells (EEs), and enterocytes. This unbiased approach recovered most of the known intestinal stem cells/enteroblast and EE markers, highlighting the high quality of the dataset, and led to insights on intestinal stem cell biology, cell type-specific organelle features, the roles of new transcription factors in progenitors and regional variation along the gut, 5 additional EE gut hormones, EE hormonal expression diversity, and paracrine function of EEs. To facilitate mining of this rich dataset, we provide a web-based resource for visualization of gene expression in single cells. Altogether, our study provides a comprehensive resource for addressing functions of genes in the midgut epithelium.

A two-step lineage reprogramming strategy to generate functionally competent human hepatocytes from fibroblasts.

Terminally differentiated cells can be generated by lineage reprogramming, which is, however, hindered by incomplete conversion with residual initial cell identity and partial functionality. Here, we demonstrate a new reprogramming strategy by mimicking the natural regeneration route, which permits generating expandable hepatic progenitor cells and functionally competent human hepatocytes. Fibroblasts were first induced into human hepatic progenitor-like cells (hHPLCs), which could robustly expand in vitro and efficiently engraft in vivo. Moreover, hHPLCs could be efficiently induced into mature human hepatocytes (hiHeps) in vitro, whose molecular identity highly resembles primary human hepatocytes (PHHs). Most importantly, hiHeps could be generated in large quantity and were functionally competent to replace PHHs for drug-metabolism estimation, toxicity prediction and hepatitis B virus infection modeling. Our results highlight the advantages of the progenitor stage for successful lineage reprogramming. This strategy is promising for generating other mature human cell types by lineage reprogramming.

Rabbit monoclonal E-cadherin antibody: A cost-effective alternative to mouse monoclonal antibody in distinguishing ductal carcinoma in situ from lobular carcinoma in situ.

Rabbit monoclonal antibody (RabMAb) demonstrates higher sensitivity without sacrificing specificity than mouse monoclonal antibody (MMAb). MMAb against E-cadherin stain is heavily utilized in distinguishing ductal carcinoma in situ (DCIS) from lobular carcinoma in situ (LCIS). We aimed to compare the E-cadherin stain using RabMAb vs MMAb in distinguishing DCIS from LCIS. One hundred and seventeen in situ breast carcinomas (55 DCIS, 58 LCIS, and 4 DCIS and LCIS) were studied. Sections from a representative block of each were stained with RabMAb [EP700Y] and MMAb [36B5]. Scanned images of stained slides were compared in tandem. All DCIS cases (59/59) showed comparable staining by RabMAb and MMAb. Comparable staining was also observed in all but one case of LCIS (61/62; 98%). One case of pleomorphic LCIS showed mostly complete, weak to moderately intense membranous staining with RabMAb and fragmented, weak membranous staining with MMAb. Consistently better staining quality was observed in slides stained by RabMAb vs MMAb. RabMAb and MMAb against E-cadherin were diagnostically equivalent with the exception of one case where RabMAb may have led to diagnostic misinterpretation. However, the not insignificant cost savings and easier interpretation using RabMAb may justify the risk of misinterpretation of increased staining in rare cases, largely avertable with proper training.

Angiomatosis of the breast: a clinicopathological and immunophenotypical characterisation of seven cases.

AIMS: Mammary angiomatosis is a rare, benign vascular lesion that morphologically mimics low-grade angiosarcoma (LGAS). To date, only occasional reports of this entity have been published, none of which included analysis by immunohistochemistry. The purpose of this study was to further characterise mammary angiomatosis by clinical, histological, and immunohistochemical means while emphasising distinguishing features from LGAS. METHODS: Seven cases of primary mammary angiomatosis were evaluated. For one patient, a subsequent recurrence was also evaluated. RESULTS: All patients were female with a median age at presentation of 51 years (range: 19-58 years). The most common clinical presentation was that of a palpable abnormality or mass (5/8) and the median primary tumour size was 3.1 cm (range: 2-9 cm). Of the six patients with follow-up, one developed a recurrence 6 years after initial presentation. Histologically, all cases were composed of variably sized ectatic, thin-walled vessels lined by flat normochromic endothelium diffusely infiltrating mammary stroma. Where present, lesional vessels infiltrated between and around terminal duct lobular units but not into individual intralobular stroma. Most cases (6/8) showed a combination of lymphatic-appearing and haemangiomatous-appearing vessels. Lymphatic-appearing vessels were D2-40 positive in all but one case. D2-40 was negative or weak in haemangiomatous-appearing vessels. All lesional vessels were CD31 positive. Ki-67 indices were <1% in all but one case (5%). CONCLUSIONS: Mammary angiomatosis is a rare vascular lesion that shares clinical, morphological and immunohistochemical features with LGAS; however, certain key traits make the distinction possible.