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Methods in Molecular Biology (Clifton,... 2019Immunohistochemistry (IHC) is a powerful technique that exploits the specific binding between an antibody and antigen to detect and localize specific antigens in cells... (Review)
Review
Immunohistochemistry (IHC) is a powerful technique that exploits the specific binding between an antibody and antigen to detect and localize specific antigens in cells and tissue, most commonly detected and examined with the light microscope. A standard tool in many fields in the research setting, IHC has become an essential ancillary technique in clinical diagnostics in anatomic pathology (Lin F, Chen Z. Arch Pathol Lab Med 138:1564-1577, 2014) with the advent of antigen retrieval methods allowing it to be performed conveniently on formalin fixed paraffin embedded (FFPE) tissue (Taylor CR, Shi S-R, Barr NJ. Techniques of immunohistochemistry: principles, pitfalls, and standardization. In: Dabbs DJ (ed) Diagnostic immunohistochemistry: theranostic and genomic applications, 3rd edn. Saunders, Philadelphia, 2010; Shi SR, Key ME, Kalra KL. J Histochem Cytochem 39:741-748, 1991) and automated methods for high volume processing with reproducibility (Prichard J, Hicks D, Hammond E. Automated immunohistochemistry overview. In: Fan L, Jeffrey P (eds) Handbook of practical immunohistochemistry: frequently asked questions, 2nd edn. Springer, New York, 2015). IHC is frequently utilized to assist in the classification of neoplasms, determination of a metastatic tumor's site of origin and detection of tiny foci of tumor cells inconspicuous on routine hematoxylin and eosin (H&E) staining. Furthermore, it is increasingly being used to provide predictive and prognostic information, such as in testing for HER2 amplification in breast cancer (Wolff AC, Hammond MEH, Hicks DG et al. Arch Pathol Lab Med 138:241-256, 2014) in addition to serving as surrogate markers for molecular alterations in neoplasms, including IDH1 and ATRX mutations in brain tumors (Appin CL, Brat DJ. Mol Aspects Med. 45:87-96, 2015). In this chapter we describe the basic methods of immunohistochemical staining which has become an essential tool in the daily practice of anatomic pathology worldwide.
Topics: Biomarkers, Tumor; Female; Humans; Immunohistochemistry; Paraffin Embedding; Prognosis; Tissue Fixation
PubMed: 30539453
DOI: 10.1007/978-1-4939-8935-5_25 -
Intensive Care Medicine Oct 2022Multiple organ failure following a septic event derives from immune dysregulation. Many of the mediators of this process are humoral factors (cytokines), which could... (Review)
Review
Multiple organ failure following a septic event derives from immune dysregulation. Many of the mediators of this process are humoral factors (cytokines), which could theoretically be cleared by direct adsorption through a process called hemoperfusion. Hemoperfusion through devices, which bind specific molecules like endotoxin or theoretically provide non-specific adsorption of pro-inflammatory mediators has been attempted and studied for several decades with variable results. More recently, technological evolution has led to the increasing application of adsorption due to more biocompatible and possibly more efficient biomaterials. As a result, new indications are developing in this field, and novel tools are available for clinical use. This narrative review will describe current knowledge regarding technical concepts, safety, and clinical results of hemoperfusion. Finally, it will focus on the most recent literature regarding adsorption applied in critically ill patients and their indications, including recent randomized controlled trials and future areas of investigation. Clinical trials for the assessment of efficacy of hemoperfusion in septic patients should apply the explanatory approach. This includes a highly selected homogenous patient population. Enrichment criteria such as applying genetic signature and molecular biomarkers allows the identification of subphenotypes of patients. The intervention must be delivered by a multidisciplinary team of trained personnel. The aim is to maximize the signals for efficacy and safety. In a homogenous cohort, confounding uncontrolled variables are less likely to exist. Trials with highly selected populations have a high internal validity but poor generalizability. The parallel design described in the figure is robust and usually is required by regulatory agencies for the approval of a new treatment. Allocation concealment and randomization are key to minimize bias such as confirmation bias, observer bias. The intervention should be delivered following a strict protocol. Deviations from the protocol might negatively influence the potential effects of the therapies. Surrogates such as cytokine measurement are adequate primary outcomes in phase 3 trials with small sample size because there is a higher likelihood of finding positive results concerning surrogate markers than in respect with clinical outcomes. Once a trial shows positive results concerning surrogate markers, a rationale for another phase 3 trial exploring clinical outcomes is built, justifying the allocation of financial sources to the intended trial.
Topics: Biomarkers; Critical Illness; Endotoxins; Hemoperfusion; Humans; Intensive Care Units
PubMed: 35984473
DOI: 10.1007/s00134-022-06810-1 -
Cancer Cytopathology May 2019With an escalating number of predictive biomarkers emerging in non-small cell lung carcinoma (NSCLC), immunohistochemistry (IHC) is being used as a rapid and... (Review)
Review
With an escalating number of predictive biomarkers emerging in non-small cell lung carcinoma (NSCLC), immunohistochemistry (IHC) is being used as a rapid and cost-effective tool for the screening and detection of many of these markers. In particular, robust IHC assays performed on formalin-fixed, paraffin-embedded (FFPE) tumor tissue are widely used as surrogate markers for ALK and ROS1 rearrangements and for detecting programmed death ligand 1 (PD-L1) expression in patients with advanced NSCLC; in addition, they have become essential for treatment decisions. Cytology samples represent the only source of tumor in a significant proportion of patients with inoperable NSCLC, and there is increasing demand for predictive biomarker testing on them. However, the wide variation in the types of cytology samples and their preparatory methods, the use of alcohol-based fixatives that interfere with immunochemistry results, the difficulty in procurement of cytology-specific controls, and the uncertainty regarding test validity have resulted in underutilization of cytology material for predictive immunocytochemistry (ICC), and most cytopathologists limit such testing to FFPE cell blocks (CBs). The purpose of this review is to: 1) analyze various preanalytical, analytical, and postanalytical factors influencing ICC results; 2) discuss measures for validation of ICC protocols; and 3) summarize published data on predictive ICC for ALK, ROS1, EGFR gene alterations and PD-L1 expression on lung cancer cytology. Based on our experience and from a review of the literature, we conclude that cytology specimens are in principal suitable for predictive ICC, but proper optimization and rigorous quality control for high-quality staining are essential, particularly for non-CB preparations.
Topics: Biomarkers, Tumor; Cytodiagnosis; Humans; Immunohistochemistry; Lung Neoplasms; Predictive Value of Tests
PubMed: 31050216
DOI: 10.1002/cncy.22137 -
Molecular and Cellular Biochemistry Mar 2021The assessment and monitoring of the tissue perfusion is extremely important in critical conditions involving circulatory shock. There is a wide range of established... (Review)
Review
The assessment and monitoring of the tissue perfusion is extremely important in critical conditions involving circulatory shock. There is a wide range of established methods for the assessment of cardiac output as a surrogate of oxygen delivery to the peripheral tissues. However, the evaluation of whether particular oxygen delivery is sufficient to ensure cellular metabolic demands is more challenging. In recent years, specific biochemical parameters have been described to indicate the status between tissue oxygen demands and supply. In this review, the authors summarize the application of some of these biochemical markers, including mixed venous oxygen saturation (SO), lactate, central venous-arterial carbon dioxide difference (PCO gap), and PCO gap/central arterial-to-venous oxygen difference (CO) for hemodynamic assessment of tissue perfusion. The thorough monitoring of the adequacy of tissue perfusion and oxygen supply in critical conditions is essential for the selection of the most appropriate therapeutic strategy and it is associated with improved clinical outcomes.
Topics: Arteries; Biomarkers; Carbon Dioxide; Glucose; Hemodynamics; Humans; Hypoxia; Lactic Acid; Microcirculation; Monitoring, Physiologic; Oxygen; Oxygen Consumption; Perfusion; Prognosis; Spectroscopy, Near-Infrared
PubMed: 33387216
DOI: 10.1007/s11010-020-04019-8 -
International Journal of Molecular... Mar 2023Soft tissue tumors are rare mesenchymal tumors with divergent differentiation. The diagnosis of soft tissue tumors is challenging for pathologists owing to the diversity... (Review)
Review
Soft tissue tumors are rare mesenchymal tumors with divergent differentiation. The diagnosis of soft tissue tumors is challenging for pathologists owing to the diversity of tumor types and histological overlap among the tumor entities. Present-day understanding of the molecular pathogenesis of soft tissue tumors has rapidly increased with the development of molecular genetic techniques (e.g., next-generation sequencing). Additionally, immunohistochemical markers that serve as surrogate markers for recurrent translocations in soft tissue tumors have been developed. This review aims to provide an update on recently described molecular findings and relevant novel immunohistochemical markers in selected soft tissue tumors.
Topics: Humans; Sarcoma; Translocation, Genetic; In Situ Hybridization, Fluorescence; Diagnosis, Differential; Soft Tissue Neoplasms; Biomarkers, Tumor
PubMed: 36983010
DOI: 10.3390/ijms24065934 -
Diagnostic Pathology Apr 2021Solitary Fibrous Tumor (SFT) is a distinct soft tissue neoplasm associated with NAB2-STAT6 gene fusion. It can involve a number of anatomic sites and exhibits a wide... (Review)
Review
The many faces of solitary fibrous tumor; diversity of histological features, differential diagnosis and role of molecular studies and surrogate markers in avoiding misdiagnosis and predicting the behavior.
BACKGROUND
Solitary Fibrous Tumor (SFT) is a distinct soft tissue neoplasm associated with NAB2-STAT6 gene fusion. It can involve a number of anatomic sites and exhibits a wide spectrum of histological features.
MAIN BODY
Apart from diversity in morphological features seen even in conventional SFT, two histologic variants (fat-forming and giant cell-rich) are also recognized. In addition, a malignant form and dedifferentiation are well recognized. Owing to diverse histological features and involvement of diverse anatomic locations, SFT can mimic other soft tissue neoplasms of different lineages including schwannoma, spindle cell lipoma, dermatofibrosarcoma protuberans, liposarcoma, gastrointestinal stromal tumor (GIST), malignant peripheral nerve sheath tumor (MPNST), and synovial sarcoma. SFT is classified as an intermediate (rarely metastasizing) tumor according to World Health Organization Classification of Tumors of Soft tissue and Bone, 5th edition. The management and prognosis of SFT differs from its malignant mimics and correct diagnosis is therefore important. Although SFT expresses a distinct immunohistochemical (IHC) profile, the classic histomorphological and IHC profile is not seen in all cases and diagnosis can be challenging. NAB2-STAT6 gene fusion has recently emerged as a sensitive and specific molecular marker and its IHC surrogate marker signal transducer and activator of transcription 6 (STAT6) has also shown significant sensitivity and specificity. However, few recent studies have reported STAT6 expression in other soft tissue neoplasms.
CONCLUSION
This review will focus on describing the diversity of histological features of SFT, differential diagnoses and discussing the features helpful in distinguishing SFT from its histological mimics.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Child; Diagnosis, Differential; Diagnostic Errors; Female; Gene Fusion; Humans; Immunohistochemistry; Male; Middle Aged; Molecular Diagnostic Techniques; Mutation; Predictive Value of Tests; Prognosis; Repressor Proteins; STAT6 Transcription Factor; Solitary Fibrous Tumors; Young Adult
PubMed: 33879215
DOI: 10.1186/s13000-021-01095-2 -
Indian Journal of Ophthalmology Apr 2023Dry eye disease (DED) is a commonly occurring, multifactorial disease characterized by reduced tear film stability and hyperosmolarity at the ocular surface, leading to... (Review)
Review
Dry eye disease (DED) is a commonly occurring, multifactorial disease characterized by reduced tear film stability and hyperosmolarity at the ocular surface, leading to discomfort and visual compromise. DED is driven by chronic inflammation and its pathogenesis involves multiple ocular surface structures such as the cornea, conjunctiva, lacrimal glands, and meibomian glands. The tear film secretion and its composition are regulated by the ocular surface in orchestration with the environment and bodily cues. Thus, any dysregulation in ocular surface homeostasis causes an increase in tear break-up time (TBUT), osmolarity changes, and reduction in tear film volume, all of which are indicators of DED. Tear film abnormalities are perpetuated by underlying inflammatory signaling and secretion of inflammatory factors, leading to the recruitment of immune cells and clinical pathology. Tear-soluble factors such as cytokines and chemokines are the best surrogate markers of disease severity and can also drive the altered profile of ocular surface cells contributing to the disease. Soluble factors can thus help in disease classification and planning treatment strategies. Our analysis suggests increased levels of cytokines namely interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-9, IL-12, IL-17A, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α); chemokines (CCL2, CCL3, CCL4, CXCL8); MMP-9, FGF, VEGF-A; soluble receptors (sICAM-1, sTNFR1), neurotrophic factors (NGF, substance P, serotonin) and IL1RA and reduced levels of IL-7, IL-17F, CXCL1, CXCL10, EGF and lactoferrin in DED. Due to the non-invasive sample collection and ease of quantitively measuring soluble factors, tears are one of the best-studied biological samples to molecularly stratify DED patients and monitor their response to therapy. In this review, we evaluate and summarize the soluble factors profiles in DED patients from the studies conducted over the past decade and across various patient groups and etiologies. The use of biomarker testing in clinical settings will aid in the advancement of personalized medicine and represents the next step in managing DED.
Topics: Humans; Dry Eye Syndromes; Tears; Cytokines; Chemokines; Biomarkers; Lacrimal Apparatus
PubMed: 37026250
DOI: 10.4103/IJO.IJO_2981_22 -
Epilepsia Aug 2013A biomarker is defined as an objectively measured characteristic of a normal or pathologic biologic process. Identification and proper validation of biomarkers of... (Review)
Review
A biomarker is defined as an objectively measured characteristic of a normal or pathologic biologic process. Identification and proper validation of biomarkers of epileptogenesis (the development of epilepsy) and ictogenesis (the propensity to generate spontaneous seizures) might predict the development of an epilepsy condition; identify the presence and severity of tissue capable of generating spontaneous seizures; measure progression after the condition is established; and determine pharmacoresistance. Such biomarkers could be used to create animal models for more cost-effective screening of potential antiepileptogenic and antiseizure drugs and devices, and to reduce the cost of clinical trials by enriching the trial population, and acting as surrogate markers to shorten trial duration. The objectives of the biomarker subgroup for the London Workshop were to define approaches for identifying possible biomarkers for these purposes. Research to identify reliable biomarkers may also reveal underlying mechanisms that could serve as therapeutic targets for the development of new antiepileptogenic and antiseizure compounds.
Topics: Animals; Anticonvulsants; Biomarkers; Brain; Clinical Trials as Topic; Cost-Benefit Analysis; Disease Models, Animal; Disease Progression; Drug Discovery; Drug Evaluation, Preclinical; Drug Resistance; Drugs, Investigational; Electroencephalography; Epilepsy; Humans; Precipitating Factors
PubMed: 23909854
DOI: 10.1111/epi.12299 -
Abdominal Radiology (New York) Mar 2022Liver fibrosis (LF) is the wound healing response to chronic liver injury. LF is the endpoint of chronic liver disease (CLD) regardless of etiology and the single most... (Review)
Review
Liver fibrosis (LF) is the wound healing response to chronic liver injury. LF is the endpoint of chronic liver disease (CLD) regardless of etiology and the single most important determinant of long-term liver-related clinical outcomes. Quantification of LF is important for staging, to evaluate response to treatment and to predict outcomes. LF is traditionally staged by liver biopsy. However, liver biopsy is invasive and suffers from sampling errors when biopsy size is inadequate; therefore, non-invasive tests (NITs) have found important roles in clinical care. NITs include simple laboratory-based serum tests, panels of serum tests, and imaging biomarkers. NITs are validated against the liver biopsy and will be used in the future for evaluation of nearly all CLDs with invasive liver biopsy reserved for some cases. Both serum tests and some imaging biomarkers such as elastography are currently used clinically as surrogate markers for LF. Several other imaging biomarkers are still considered research and awaiting clinical application in the future. As the evaluation of imaging biomarkers will likely become the norm in the future, understanding pathogenesis of LF is important. Knowledge of properties measured by imaging biomarkers and its correlation with LF is important to understand the application of NITs by abdominal radiologists. In this review, we present a brief overview of pathogenesis of LF, spatiotemporal evolution of LF in different CLD, and severity assessment with liver biopsy. This will be followed by a brief discussion on properties measured by imaging biomarkers and their relationship to the LF.
Topics: Biomarkers; Biopsy; Elasticity Imaging Techniques; Humans; Liver; Liver Cirrhosis; Liver Diseases
PubMed: 35022806
DOI: 10.1007/s00261-021-03396-y -
The Pan African Medical Journal 2023
Topics: Child; Humans; Adiposity; Blood Pressure; Obesity; Hypertension; Biomarkers; Body Mass Index; Risk Factors
PubMed: 38465005
DOI: 10.11604/pamj.2023.46.114.42371