Expression Of S-100 Protein Research Articles

Soft Tissue Special Issue: Biphenotypic Sinonasal Sarcoma: A Review with Emphasis on Differential Diagnosis.

Biphenotypic sinonasal sarcoma is an anatomically restricted low-grade malignant neoplasm with dual neural and myogenic differentiation composed of a monotonous population of spindled cells with herringbone/fascicular architecture. These tumors demonstrate a unique immunoprofile with relatively consistent S100-protein and actin expression in conjunction with more variable desmin, myogenin and myoD1 staining. SOX10 is uniformly negative. Genetically, the majority of tumors harbor PAX3-MAML3 fusions, with alternate PAX3 partners including FOXO1, NCOA1, NCOA2 and WWTR1. Although the differential diagnosis of BSNS is broad, careful morphologic inspection together with targeted ancillary studies is often sufficient to arrive at the correct diagnosis. As these tumors have significant local recurrence rates but lack metastatic potential, awareness and accurate diagnosis of this rare and newly described neoplasm is critical for appropriate management.

Low concentrations of morphine enhanced the neuroglia-like differentiation

The present study was undertaken to evaluate the effects of different concentrations of morphine in chronic manner on neuroglial differentiation in PC12 cells. PC12 cells were cultured in RPMI 1640 culture medium including 0.02 % bovine serum albumin together with different concentrations of morphine for 12 days. Cytotoxicity was performed by lactate dehydrogenase assay. Cell death was performed by PI/Hoechst staining assay. Neuroglial differentiation was performed by Nestin, Tuj-1, MAP-2, S-100 and GFAP Immunocytochemistry assay. Data showed that morphine either at low or high concentration activated opioid receptors, which resulted in a decrease of cytotoxicity and cell death and induction of Nestin, Tuj-1, MAP-2, Neurofilament-M (NF-M), GFAP and S-100 protein expression as compared in treated cells with the control (untreated cells) (p<005). It can be concluded that low concentrations of morphine in chronic manner stimulate the neuroglial-like differentiation by activating protein expression and survival-promoting signaling in PC12 cells with opioid receptor-dependent mechanism (Fig. 8, Ref. 36). Text in PDF www.elis.sk.

Breast schwannoma – a rare entity

Introduction: Schwannoma is a benign tumor originating from Schwann cells present in the myelin sheath of peripheral nerves. Breast presentation is rare, and its clinical manifestation can mimic that of breast carcinoma. Objectives: To report the case of a patient with breast Schwannoma. Method/Case report: T.S.L., 14 years old, presented a nodule in the left breast (LB) with local growth for 2 months. Ultrasound (US) revealed a cystic formation in the lower outer quadrant of 1.8x1.3 cm, BI-RADS 2. Physical examination indicated a nodular skin lesion next to the LB fold, with 2 cm at 5 h, 7 cm from the nipple. After the surgical excision of the nodule, anatomopathological examination showed a spindle cell neoplasm without nodular-pattern atypia or malignancy characteristics. Immunohistochemistry (IHC) confirmed the Schwannoma diagnosis. Considering this scenario, annual control was started, and the patient has no evidence of the disease after 5 years of diagnosis. Results/Discussion: Schwannoma is a typically benign tumor originating from Schwann cells in the myelin sheath of the nerves. It may result from the parasympathetic or sympathetic division of the autonomic nervous system of the organ. It is one of the few truly encapsulated tumors of the human body and almost always solitary. It is usually located in the trunk, flexor surfaces, retroperitoneum, and rarely in the breast, representing approximately 2.6% of Schwannoma cases. It affects individuals aged 30 to 50 years, with equal incidence in both men and women. The skin lesion presents as a sessile, asymptomatic nodule of 1–3 cm and slow growth. Pain and sensitivity may be present when tumor growth causes nerve compression. Mammography (MMG) shows well-circumscribed opacity, with a density similar to that of soft tissue. US usually reveals well-defined, hypoechoic, solid lesions and can include the target sign, posterior acoustic enhancement, and continuity with peripheral nerves. The definitive diagnosis is made histologically, and the differential diagnosis involves other spindle cell neoplasms, such as fibroadenoma, phyllodes tumor, leiomyoma, fibromatosis, and, rarely, metaplastic carcinoma. Fine-needle aspiration biopsy (FNAB) showed palisading fibrillar cells with non-atypical spindle-shaped nuclei forming Verocay bodies. IHC indicates intense and uniform expression of S-100 protein. Malignant transformation occurs in 3–10% of cases, with high cellular proliferation, atypical mitotic activity, cellular and nuclear pleomorphism, and foci of necrosis. The treatment of choice is surgical excision of the lesion. Tumor recurrence is low and associated with the mitotic index. Conclusion: The case reported and publications found bring to light the discussion on diagnosis and treatment of breast Schwannoma, a rare and benign neoplasm in this location.

Rektumun Benign Tümörünün Malign Görüntüsü

Rectal schwannomas are rare mesenchymal tumour of the gastrointestinal tract. They are scarcely identified in the low rectum as compared to the proximal tract. If present, huge tumour tends to be symptomatic leading to obstruction, bleeding, and tenesmus. We highlight a 74-year-old man with malignant presentations mimicking low rectal cancer. Colonoscopy revealed a huge pedunculated polyp measuring 10 x 8 cm with a diagnosis of benign tumour of schwannoma upon punch biopsy. Transanal excision was made after failure of endoscopic resection. Microscopic evaluation of the tumour showed a benign nerve sheath tumour of schwannoma supported by positive S100 protein expression. His recovery was excellent, hence he was discharged on the following day. There are no similar symptoms and tumour recurrence on follow up. A huge rectal tumour is not always malignant. Despite their rarity, schwannomas can manifest as malignant features. In case of tumour that mimics rectal carcinoma, preoperative diagnosis is very important for a management plan. The definitive histological diagnosis is based on the morphological features with diffuse positivity of S100 from immunohistochemical study. Surgical resection either endoscopic or transanal approach is the mainstay of treatment, especially when dealing with local complication caused by the huge bulk of tumour.

820: Elevated plasma S100 protein levels in preterm gestations with histologic chorioamnionitis

Histologic chorioamnionitis (HCA) is an inflammatory process that may be clinically silent and linked with preterm birth. S100 proteins are inflammatory markers which have been identified in amniotic fluid of mothers affected by HCA. We explored the relationship of S100A8 and S100A12 levels in mother-baby pairs with HCA compared to unexposed controls. We hypothesized that S100 protein expression levels are increased in mother-baby pairs affected by HCA. This is a prospective observational cohort of singleton or uncomplicated twin gestations from 230/7 to 346/7 weeks with preterm labor or preterm premature rupture of membranes (PPROM). Exclusion criteria included any maternal inflammatory disorder. Maternal peripheral blood was obtained within 24 h peripartum and venous umbilical cord blood samples were obtained at delivery. Diagnoses of maternal (M-HCA) or fetal (F-HCA) or the absence of HCA (Ctrl) were determined by placental examination per Redline HCA definitions (Redline 2012). S100A8 and S100A12 levels were measured by commercial ELISA. Data were analyzed using appropriate statistical methods. S100 protein levels were determined in plasma samples from 41 mother-baby pairs (7 M-HCA, 22 F-HCA, 12 Ctrl). Demographic data, PPROM incidence and gestational age at delivery were similar between groups. In F-HCA, S100A8 levels were increased 2-fold in maternal blood (p< .05) and 4-fold in cord blood (p< .001) relative to Ctrl. In F-HCA, maternal and cord blood S100A8 levels were similar, but in M-HCA, maternal levels were higher (p=.01). Cord blood S100A12 levels were 4-fold higher with F-HCA vs. Ctrl (p< .0001). In contrast, maternal S100A12 levels were similar across conditions. Fetal HCA is associated with elevated S100A8 and S100A12 levels in maternal and neonatal plasma. Our data suggest that maternal S100A8 blood levels may uniquely identify fetal HCA, a diagnosis that currently depends on postpartum placental analysis. Studies to establish the utility of S100A8 as a biomarker of HCA in a more extensive population are planned.

Immunohistochemical analysis of 36 cases of chondroblastomas: A single institutional experience

Chondroblastoma is a relatively uncommon, primary benign bone tumor, frequently identified in young individuals. Despite its classical radiologic and histopathological features, at times, it is fraught with a diagnostic challenge, especially differentiating it from a giant cell tumor of bone (GCTB); an osteosarcoma and a chondrosarcoma. Lately, few studies have shown the diagnostic utility of immunohistochemical (IHC) expression DOG1 antibody in chondroblastomas. The present study was undertaken to evaluate IHC expression of S100 protein, DOG1 and p63 in 36 chondroblastomas.From January 2013 to July 2019 (6-year duration), 106 chondroblastomas were diagnosed, with IHC staining performed in 36 cases. Conventional Hematoxylin and Eosin stained microsections and IHC stained sections were reviewed in 36 cases. IHC staining of p63 (intranuclear), S100 protein (nuclear and cytoplasmic) and DOG1 (cytoplasmic membranous) was recorded in various cases.Seventy-four tumors occurred in males and 32 in females, within age-range of 7–55 years (average = 18.6), frequently in tibia (33/106; 31.1%), followed by femur (26, 24.5%) humerus (22, 20.7%), calcaneum (5) and scapula (4). IHC staining for S100P was positive in 33/36cases (91.7%); DOG1 in 16/19 (84.2%) cases and p63 in 10/15cases (66.6%). DOG1 immunostaining was negative in 25 various other tumors. Sensitivity and specificity for S100P, DOG1and p63 in chondroblastomas was (91.6%, 59.3%); (84.2%, 100%) and (66.6%, 46.6%), respectively. P63 was positively expressed in 15/27 (55.5%) GCTBs.S100 protein and DOG1 can be utilized for a confirmatory diagnosis of a chondroblastoma, especially for differentiating it from its other differentials, such as GCTB, in view of certain associated therapeutic implications. P63 is not useful in that scenario.

Platelet-rich plasma can release nutrient factors to promote facial nerve crush injury recovery in rats.

Objectives:To evaluate the effects of platelet-rich plasma (PRP) on promoting neural repair after facial nerve compression in rats and the mechanism by which this occurs.Methods:Adult Wistar rats (n=100) were divided into 3 groups: healthy controls, surgery-only, and surgery+PRP groups. The rats underwent nerve crush injury to establish a facial palsy model. The blood from the rats was used to prepare the PRP for application to the injury site. The evaluation methods included vibrissae movement, eyelid closure, and electrophysiology. Electron microscopy, immunohistochemistry, and real-time polymerase chain reaction (PCR) were used to detect nutrient factor expression in the brain and nerve sections. This study was conducted in Shandong Provincial ENT Hospital Affiliated to Shandong University, Shandong, China between January and November 2018.Results:Platelet-rich plasma promotes the recovery of vibrissae movement, eyelid closure, and electrophysiological function in a rat model of nerve crush injury. Hematoxylin and eosin staining, toluidine blue staining, and electron microscopy showed significant recovery of Schwann cells and axons in the PRP group. Polymerase chain reaction results showed that PRP releases growth factors, which include nerve growth factor and brain-derived neurotrophic factor. Immunohistochemistry also demonstrated higher levels of S-100 protein expression in the PRP group compared to the other groups.Conclusions:Platelet-rich plasma releases nutrient factors in the brainstem, and the use of PRP can promote injury recovery.

Fetal Megacystis: A New Morphologic, Immunohistological and Embriogenetic Approach

Congenital anomalies of the kidney and urinary tract (CAKUT) include isolated kidney malformations and urinary tract malformations. They have also been reported in Prune-Belly syndrome (PBS) and associated genetic syndromes, mainly 13, 18 and 21 trisomy. The AA focuses on bladder and urethral malformations, evaluating the structural and histological differences between two different cases of megacystis. Both bladders were examined by routine prenatal ultrasound screening and immunohistochemistry, comparing the different expression of smooth muscular actin (SMA), S100 protein and WT1c in megacystis and bladders of normal control from fetuses of XXI gestational age. Considering the relationship between the enteric nervous system and urinary tract development, the AA evaluated S100 and WT1c expression both in bladder and bowel muscular layers. Both markers were not expressed in the bladder and bowel of PBS associated with anencephaly. In conclusion, megacystis could be considered only a macroscopic definition, concerning the size of the fetal bladder rather than the embryologic origin; it may be a single or multiple malformation; the possible association with the bowel and/or encephalic malformations will decide the outcome and prognosis in fetal megacystis.

Microenvironmental Triggers Induce a Chemoresistant, Differentiated Subset of S100A8/A9high AML Cells Via the Jak/STAT3 Signaling Axis

Introduction: The bone marrow stromal niche can serve as a protective environment in hematological malignancies such as AML. Intensive research of the bidirectional interactions between leukemic blasts and stromal cells already highlighted numerous mechanisms how malignant cells are capable of shaping their local milieu in an opportunistic fashion. However, the complex mechanisms remain to be fully elucidated. Previously, we found two small intracellular calcium-sensing molecules, S100A8 and S100A9, among the top upregulated genes in primary AML blasts upon stromal contact in an unbiased analysis. They are members of the S100 protein family that can modulate cellular responses such as proliferation, migration, inflammation, and differentiation. Dysregulation of S100 protein expression is described as a common feature in several human cancers. Particularly, expression of S100A8 in leukemic blasts predicts poor survival in de novo AML patients. Thus, we aimed to decipher the underlying pathways of the stroma-mediated S100A8/A9 upregulation as well as its functional consequences. Methods: We cultured AML cell lines in absence or presence of bone marrow stroma cell-conditioned medium. Subsequent, AML cells were analyzed for alterations in intracellular signaling pathways and metabolic characteristics by means of flow cytometry, fluorescence microscopy and quantitative real-time PCR. Additionally, AML cells were analyzed for their resistance towards chemotherapy under the very same culture conditions. Moreover, matched pairs of patient-derived AML samples from the peripheral blood and the bone marrow were compared for key findings from the in vitro analyses. Results: The previously seen upregulation of S100A8 and S100A9 in primary AML blasts upon stromal contact could be confirmed in AML cell lines both on the mRNA and the protein level and proved to be contact-independent and reversible. Interleukin 6-mediated triggering of the Jak/STAT3 signaling was shown to be one major pathway of this induction. The S100A8/A9high subpopulation is characterized by profound metabolic alterations, and by increased surface levels of maturation markers (i.e. CD11b and CD14) both conferring chemoresistance. Strikingly, both differentiation and chemoresistance could be reversed by inhibition of Jak/STAT signaling or metabolic interference. Ultimately, elevated frequencies of S100A8/A9high AML blasts with increased surface levels of maturation markers could be detected in bone marrow-derived specimen compared to matched samples from the peripheral blood in the same patient. Conclusion: We could demonstrate that bone marrow stroma-induced S100A8/A9high AML cells show increased maturation and chemoresistance which both can be targeted by metabolic or oncogenic signaling inhibition representing additional possible targets for further pre-clinical exploration. Disclosures Bruns: Morphosys AG: Research Funding.

Melatonin activates the vascular elements, telocytes, and neuroimmune communication in the adrenal gland of Soay rams during the non-breeding season.

The adrenal glands of 15 adult Soay rams were used to study the effect of melatonin on their vascular elements and cellular organization. A significant increase in the cross-sectional area of the blood sinusoids was demonstrated after melatonin administration. The vimentin-expressing mesenchymal cells were increased in the melatonin-treated group. Intensive S-100 protein expression was observed in the sustentacular cells and telocytes (TCs) of the treated groups. Moreover, S-100 protein expressed intensively in the dendritic cells that distributed around the blood sinusoids. Dendritic cells showed positive immunoreactivity for CD8 and CD103. Many dendritic cells with well-defined processes were observed close to the nerve fibers after melatonin administration. A significant increase in the number and diameter of dendritic cells after melatonin treatment was demonstrated. Many highly active TCs were observed in the medulla of the treated group, which were characterized by long telopodes (Tps) containing abundant secretory vesicles that released into the extracellular milieu and towards the dendritic cells. In the melatonin-treated groups, the nerve fibers showed a significant increase in their cross-sectional area accompanied by an increase in the activity of Schwann cells and neighboring dendritic cells. In the treated group, TCs and DCs appear to contribute to angiogenesis. A planner contact between Tps and the stem cell was demonstrated in the treated group. Melatonin induced a stimulatory action on the vascular and neuronal elements of the adrenal gland. Moreover, it enhances the activity of a variety of cells including telocytes, dendritic, sustentacular, and Schwann cells.

Hybrid schwannoma/perineurioma: a clinicopathological analysis of 35 cases

Objective: To investigate the clinical pathological features, pathological diagnosis and differential diagnosis of hybrid schwannoma/perineurioma. Methods: The clinicopathological data of 35 cases were collected at Fudan University Shanghai Cancer Center, from October 2010 to August 2017; morphological observation and immunohistochemical staining were performed, and the literatures were also reviewed. Results: There were 7 males and 28 females (male∶female=1∶4), patients with onset age ranging from 3 to 81 years(mean=36 years). Of 35 tumors, 11 cases occurred in the head and neck, 10 in the extremities, 9 in the trunk, 4 in the intestine, and 1 in the labiamajora, respectively. Clinically, most patients presented as a slowly growing dermal nodule, sometimes associated with pain. The duration of symptoms ranged from 1 month to 20 years before excision. Tumor size ranged from 0.8 cm to 6.0 cm (mean=2.6 cm). Microscopically, the tumors were usually well circumscribed but unencapsulated. At low power, most tumors were located in the dermis or subcutis, and several cases in the submucosal tissues. The tumors were composed of fascicular, storiform or whorled growth of closely intermixed plump spindle cells and slender spindle cells. The plump spindle cells had ill-defined eosinophilic cytoplasm with larger tapered or wavy nuclei, whereas the slender spindle cells had comparatively delicate nuclei with elongated cytoplasmic processes. Tumor cells had no obvious atypia, and mitoses were rare. Scattered large cells with degenerative nuclear atypia were seen in some cases. By immunohistochemistry, most of plump spindle cells showed strong staining of S-100 protein(35/35) and SOX10(8/9), whereas slender spindle cells stained variably for epithelial membrane antigen(31/35), CD34(32/33), Claudin-1 (15/15) and GLUT-1(8/8). Ki-67 proliferation index were all less than 5%. Follow-up data available in 16 patients (range 4 to 72 months; mean=46 months) were all free of disease, and one case developed local recurrence. Conclusions: Hybrid schwannoma/perineuriomaisa benign nerve sheath tumor that typically manifests as a dermaland subcutaneous tumor, less frequently may affect uncommon sites such as the nasal cavity, the gastro-intestinal tract, and the external genital areas. The tumors consisted of intimately admixed plump-spindled schwannian cells and slender-spindled perineurial cells showing dual differentiation of strong S-100 protein and SOX10 expression in the former component and variable immunoreactivity of epithelial membrane antigen, Claudin-1 and CD34 in the latter. It should be aware of the possibility of potentially misinterpretation of hybrid schwannoma/perineurioma as dermatofibrosarcoma protuberans and solitary fibrous tumor and so on.

Two Synchronous Pituitary Adenomas Causing Cushing Disease and Acromegaly

To report the first case of 2 synchronous pituitary adenomas, 1 corticotroph and 1 somatotroph, with distinct molecular lineages confirmed by differential hormone and S-100 protein expression. A case report followed by a literature review are presented. A 68-year-old woman presented for evaluation of resistant hypertension. Biochemical testing demonstrated adrenocorticotropic hormone (ACTH)-dependent hypercortisolemia and growth hormone (GH) excess. Pituitary magnetic resonance imaging (MRI) revealed a 2 cm left sellar lesion consistent with a pituitary macroadenoma. The patient therefore underwent transsphenoidal surgery for a presumed cosecreting ACTH and GH macroadenoma. Tumor immunohistochemical staining (IHC) was positive for ACTH, but negative for GH. Postoperative biochemical testing confirmed remission from Cushing disease, but the insulin-like growth factor 1 (IGF-1) level remained elevated. Postoperative MRI demonstrated a small right sellar lesion that, in retrospect, had been present on the preoperative MRI. Resection of the right lesion confirmed a GH-secreting adenoma with negative ACTH staining. After the second surgery, the IGF-1 level normalized and blood pressure improved. Further pathologic examination of both surgical specimens demonstrated differential expression of S-100 protein, a folliculostellate cell marker. Reverse transcription polymerase chain reaction of messenger ribonucleic acid from the left sellar lesion was positive for ACTH and negative for GH, confirming the IHC results. Germline mutations in genes known to be associated with pituitary adenoma syndromes (MEN1, CDC73, CDKN1A, CDKN1B, CDKN2B, CDKN2C, and AIP) were not detected. Although the pathogenesis of synchronous pituitary adenomas has not been fully elucidated, this case report suggests that they can have distinct molecular lineages.

Secretory Carcinoma of the Skin: Report of 6 Cases, Including a Case With a Novel NFIX-PKN1 Translocation.

Secretory carcinoma of the skin is a rare adnexal carcinoma, which is morphologically and immunohistochemically identical to secretory carcinoma of the breast and is associated with the presence of t (12;15) translocation, resulting in the ETV6-NTRK3 gene fusion. Nineteen cases of primary cutaneous secretory carcinoma have been previously published in the literature. In this study, we describe 6 new cases of secretory carcinoma of the skin. The study group consisted of 5 female patients and 1 male patient, ranging in age from 57 to 98 years (mean: 74.2, median: 74). Locations included the axilla (2), neck, eyelid, thigh, and nipple base, each one. Microscopically, all but 1 tumor were well circumscribed and nonencapsulated and exhibited characteristic abundant secretions within the microcystic and tubular spaces comprised by bland oval, round to cuboidal neoplastic cells. In addition, solid areas and focal pseudopapillae were seen, and, in 1 case, a focal mucinous component with small lakes of mucin containing small tumor nests or tubules of the neoplastic cells was present. The remaining neoplasm was mostly solid and papillary, with only few characteristic lumina containing secretions. Immunohistochemically, all cases expressed S-100 protein, mammaglobin, STAT5, GATA3, and NTRK. ETV6-NTRK3 gene fusion was detected in 5 cases, whereas, in the remaining tumor, a novel NFIX-PKN1 gene fusion was found.

Effect of Local and Systemic Dimethylsulfoxide on Peripheral Nerve Repair: A Controlled Randomized Experimental Study

Introduction We investigated the possible beneficial effect of dimethylsulfoxide (DMSO) on peripheral nerve repair in rats. Methods: Seventy rats were divided into four groups: control, sham, DMSO-L, and DMSO-IP. Except in the control group, nerve repair was done at the right sciatic nerve. DMSO was administered locally and intraperitoneally for 12 weeks to the DMSO-L and DMSO-IP groups, respectively. No therapeutic agent was administered to the other groups. Nerve regeneration was assessed by behavioral, electrophysiological, histopathological, and immunohistochemical tests. Results: With the exception of S-100 protein expression, all results indicate that DMSO has a beneficial effect on peripheral nerve regeneration. Functional nerve recovery was notably more evident in the DMSO-L than in the DMSO-IP group. Under macroscopic examination, nerve scores of the regeneration area in the DMSO-L group was also better than in the others. Discussion: We believe that DMSO can improve peripheral nerve regeneration in rats.

Ethyl Acetate Fraction from Trichilia catigua Confers Partial Neuroprotection in Components of the Enteric Innervation of the Jejunum in Diabetic Rats.

Diabetes causes damage to the enteric nervous system. The enteric nervous system consists of neurons and enteric glial cells (EGCs). The present study evaluated the effects of an ethyl-acetate fraction (EAF) from Trichilia catigua (T. catigua; 200 mg/kg) on the total population of enteric neurons (HuC/D-immunoreactive [IR]) and EGCs (S100-IR and glial fibrillary acidic protein [GFAP]-IR) in the total preparation and jejunal mucosa in diabetic rats. The animals were distributed into four groups: normoglycemic rats (N), diabetic rats (D), normoglycemic rats that received the EAF (NC), and diabetic rats that received the EAF (DC). The jejunum was processed for immunohistochemistry to evaluate HuC/D, S100, and GFAP immunoreactivity. The expression of S100 and GFAP proteins was also quantified by Western blot. The D group exhibited a decrease in the number of neurons and EGCs, an increase in the area of cell bodies, an increase in S100 protein expression, a decrease in GFAP protein expression, and a decrease in S100-IR and GFAP-IR EGCs in the jejunal mucosa. The DC group exhibited a decrease in the number of neurons and EGCs, a decrease in the area of cell bodies, a decrease in S100 and GFAP protein expression, and a decrease in S100-IR and GFAP-IR EGCs in the jejunal mucosa. The NC group exhibited maintenance of the number of neurons and EGCs, an increase in the area of cell bodies, and a decrease in S100 and GFAP protein expression. The EAF from T. catigua partially conferred protection against diabetic neuropathy in the enteric nervous system.

Diagnosis of Hirschsprung's Disease by Immunostaining Rectal Suction Biopsies for Calretinin, S100 Protein and Protein Gene Product 9.5.

Hirschsprung's disease (HD) is a congenital intestinal disease that is clinically manifested as an inability to pass meconium in infants or as long-term constipation in children. Rectal suction biopsy (RSB) to determine the absence of ganglion cells and neural hypertrophy is the most accurate test for the diagnosis of HD at present. Traditional hematoxylin-eosin staining lacks sensitivity and specificity. Acetylcholinesterase staining cannot be widely used due to its complex process. Our novel protocol of immunostaining for calretinin, S100 protein, and protein gene product 9.5 (PGP9.5), which we conducted on RSBs, exhibits high sensitivity and specificity rates of 96.49% (95% confidence interval, 0.88-0.99) and 100% (95% confidence interval, 0.97-1.00), respectively. The HD-affected segments often present as the absence of the expression of calretinin, S100 protein, and PGP9.5, which are markers of neural hypertrophy in the submucosal tissue. This protocol describes the detailed operating process of this new diagnostic method.

Cutaneous Pigmented Neurofibroma in a Pig – Morphology and Immunohistochemical Profile

Peripheral nerve sheath tumours are rare in pigs. In the present case, a juvenile female hybrid pig showed a solitary, pigmented, cutaneous mass. Histologically, it consisted of clustered melanin-laden, epithelioid cells as well as spindle cells forming bundles and nodules. The latter were surrounded by perineurial-like cells. Single Wagner-Meissner-like corpuscles were present. Immunohistochemically, the epithelioid cells expressed S100 protein, melan A and the p75 neurotrophin receptor (p75NTR). The spindle cells expressed S100, sex determining region Y-box 2, p75NTR, Krox20, growth associated protein 43 and glial fibrillary acidic protein. Perineurial-like cells were positive for p75NTR, α-smooth muscle actin and cytokeratin. Taken together, the histological und immunohistochemical findings support the diagnosis of a cutaneous pigmented neurofibroma.

Immunohistochemical detection of alpha-smooth muscle actin and S-100 in bovine mammary gland with mastitis

Fibrosis is a common finding in chronic mastitis. Epithelial-mesenchymal transition (EMT) plays a prominent role in fibrogenesis in adult tissues. The aim of this study was to investigate whether EMT occurs in bovine mastitis by assessing the expression or localization of alpha-smooth muscle actin (alpha-SMA), S-100 protein and caspase-3. Two normal bovine mammary gland tissue samples and five mastitic samples were used in the study. Antibodies to alpha-SMA, S-100 and caspase-3 were used for immunohistochemical studies. In mastitis there was increased expression of S-100 in the alveolar epithelial cells. Alpha-SMA was highly expressed in the areas where there is fibrosis in chronic mastitis. Further caspase-3 was observed in alveolar cells in mastitic tissue. Overexpression of S-100 and alpha-SMA directly correlates to the severity of mastitis.S-100 and alpha-SMA may serve as biomarkers to know the extent of tissue structural changes in mastitis. EMT could be one of the mechanistic pathways underlying the pathogenesis of fibrosis in mastitis.

New fusion sarcomas: histopathology and clinical significance of selected entities

Many sarcomas contain gene fusions that can be pathogenetic mechanisms and diagnostic markers. In this article we review selected fusion sarcomas and techniques for their detection. CIC-DUX4 fusion sarcoma is a round cell tumor now considered an entity separate from Ewing sarcoma with a more aggressive clinical course, occurrence in older age, and predilection to soft tissues. It is composed of larger cells than Ewing sarcoma and often has prominent necrosis. Nuclear DUX4 expression is a promising immuno histochemical marker. BCOR-CCNB3 fusion sarcoma is cyclin B3-positive, usually occurs in bone or soft tissue of children, and may mimic a poorly differentiated synovial sarcoma. EWSR1-NFATC2 sarcoma may present in bone or soft tissue. It is typically composed of small round cells in a trabecular pattern in a myxoid matrix resembling myoepithelioma. ACTB-GLI1 fusion sarcoma may mimic a skin adnexal carcinoma, showing focal expression of epithelial markers and S100 protein. NTRK-fusion sarcomas include, in addition to infantile fibrosarcoma with ETV6-NTRK3 fusion, LMNA-NTRK1 fusion sarcoma, a low-grade spindle cell sarcoma seen in peripheral soft tissues in children and young adults. Methods to detect gene fusions include next-generation sequencing panels, anchored multiplex polymerase chain reaction systems to detect partner for a known fusion gene, and comprehensive RNA sequencing to detect virtually all gene fusions. In situ hybridization testing using probes for both fusion partners can be used as an alternative confirmation technique, especially in the absence of satisfactory RNA yield. In addition, fusion protein-related and other immunohistochemical markers can have a high specificity for fusion sarcomas.

Targeted Mass Spectrometry of S100 Proteins.

The S100 protein family has attracted great interest in the field of biomarker research, and a growing number of studies reveal dysregulation of many of the 21 S100 protein isoforms in various human diseases. In cancer, S100 protein expression has been associated with tumor growth, progression, and response to treatment. Some S100 proteins are also considered candidate therapeutic targets. From an analytical perspective, multiplexed analysis of the family-wide S100 protein expression is challenging due to their relatively small size and high-sequence identity. Here we describe a mass spectrometry method using selected reaction monitoring which enables the targeted, multiplexed detection and quantitation of the entire S100 protein family in cell lines and tissue samples.