Cancer Diagnostics Solutions
The S100 protein family comprises calcium-binding proteins, including members such as calmodulin and troponin C. S100A is a heterodimer consisting of one alpha and one beta subunit, whereas S100B is a homodimer composed exclusively of beta subunits. S100 proteins are also expressed in antigen-presenting cells, including Langerhans cells within the epidermis and interdigitating dendritic cells located in the paracortical region of lymph nodes.
S100 calcium-binding protein B (S100?) is a member of the multifunctional S100 protein family.1-3 It plays diverse roles in cellular processes, acting as a stimulator of proliferation and migration while inhibiting apoptosis and differentiation in various cell types.
These include astrocytes, Schwann cells, chondrocytes, adipocytes, specific neuronal populations, melanocytes, Langerhans cells, histiocytes, epithelial cells, and myoepithelial cells.1-3 S100? is also expressed in neoplasms originating from these cell types, making it a valuable marker for identifying melanoma and various nervous system tumors.1-3 Notably, S100? is a highly sensitive marker for malignant melanoma, including desmoplastic and metastatic variants, despite its widespread expression..
S100B protein is part of the S100 family of proteins, which are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100B is a calcium binding peptide. S100B has been implicated in having many functions including neurite expansion, proliferation of melanoma cells, inhibition of protein kinase c-mediated phosphorylation, astrocytosis, axonal proliferation, inhibition of microtubule assembly and stimulation of Calcium ion fluxes. S100B is also associated with neurodegenerative diseases like Alzheimer's disease or other chronic neurological diseases. Apart from glial cell expression, S100B is also expressed in melanocytes, and can be used as a diagnostic tool for malignant melanoma
Sal-like protein 4 (SALL4) is a transcription factor encoded by a member of the Spalt-like (SALL) gene family, SALL4. There are four human SALL proteins (SALL1, 2, 3, and 4) with structural homology and playing diverse roles in embryonic development, kidney function, and cancer. SALL4 antibody expression is low to undetectable in most adult tissues with the exception of germ cells and human blood progenitor cells. In normal testicular tissue, positive, weak SALL4 staining is observed in spermatogonia. In addition, a few (<5%) primary spermatocytes show dot-like weak SALL4 staining. Secondary spermatocytes, spermatids, spermatozoa, and Sertoli cells are negative for anti-SALL4. Leydig cells, rete testis, epididymis, spermatic cord fibroblasts, blood vessels, and hematopoietic cells are negative for SALL4.
SATB2 is a DNA binding protein that specifically binds nuclear matrix attachment regions. It is involved in transcription regulation and chromatin remodeling. SATB2 expression in colorectal carcinomas (CRC) is correlated with good prognosis and in laryngeal squamous cell carcinoma it functions as a tumor suppressor wherein loss of expression is positively correlated with high tumor grade and recurrence. Moreover, SATB2, in combination with CK20, could identify almost all CRC s.
Special AT-rich sequence-binding protein 2 (SATB2) is a nuclear matrix-associated transcription factor encoded by the SATB2 gene. It binds selectively to matrix attachment regions (MARs) and is involved in transcriptional regulation and chromatin remodeling. Mutations or deletions affecting SATB2 have been implicated in craniofacial abnormalities, including cleft or high-arched palate, particularly in individuals with 2q32q33 microdeletion syndrome. SATB2 is a highly tissue-specific marker with restricted expression in the glandular epithelium of the lower gastrointestinal (GI) tract, particularly the colon and rectum. Immunohistochemically, SATB2 is a sensitive and specific marker for colorectal adenocarcinomas, including poorly differentiated tumors. When used in combination with CK20 and Cadherin-17, it enhances the diagnostic accuracy for identifying tumors of colorectal origin. SATB2 expression is typically absent in upper GI tract carcinomas, pancreatic ductal adenocarcinomas, and most non-colorectal primary adenocarcinomas such as those of the ovary and lung. Furthermore, SATB2 is useful in distinguishing colorectal neuroendocrine tumors from neuroendocrine neoplasms of the pancreas, upper GI tract, and lungs, where it is generally negative. In addition to epithelial tumors, SATB2 serves as a sensitive immunohistochemical marker for osteoplastic differentiation in benign and malignant mesenchyme tumors, expanding its diagnostic application.
Complex II of the mitochondrial respiratory chain, also known as succinate dehydrogenase (SDH), catalyzes the oxidation of succinate to fumarate within the tricarboxylic acid (TCA) cycle and concurrently transfers electrons from FADH? to coenzyme Q (ubiquinone). This multi-subunit complex comprises four nuclear-encoded proteins and is embedded within the inner mitochondrial membrane. The iron-sulfur (Fe-S) subunit, which is highly evolutionarily conserved, harbors three cysteine-rich motifs that coordinate the Fe-S clusters essential for electron transfer. Both sporadic and germline mutations in genes encoding subunits of this complex have been implicated in the pathogenesis of paragangliomas and pheochromocytomas, underscoring a mechanistic association between mitochondrial dysfunction and oncogenic transformation
The serum amyloid A (SAA) protein family consists of a group of apolipoproteins with differential expression patterns, including the acute-phase isoforms SAA1 and SAA2 of which SAA1 predominates in the plasma and the constitutively expressed SAAs. While hepatic synthesis is the principal source for both acute-phase and constitutive SAAs, extrahepatic expression has also been documented. During inflammatory responses, circulating SAA levels can increase by up to 1000-fold. Numerous studies have highlighted the clinical relevance of SAA in the diagnosis and monitoring of various pathological conditions. Notably, elevated SAA concentrations may be observed even in the presence of normal C-reactive protein (CRP) levels, reflecting the earlier and more pronounced acute-phase response of SAA relative to CRP. Emerging research suggests an expanded functional and regulatory role for SAA beyond its traditional acute-phase reactant classification.
The gene encodes a glycoprotein that belongs to the pentraxin family, characterized by a conserved pentameric quaternary structure. Members of this protein family exhibit significant sequence homology, likely arising from ancestral gene duplication events. The interaction of this protein with amyloid-associated cross-? sheet structures indicates a potential molecular chaperone function in pathological contexts. Additionally, it has been implicated in the regulation of chromatin catabolism. Experimental evidence demonstrates that the protein associates with apoptotic cells at early stages of cell death, suggesting a role in apoptotic cell recognition and clearance in vivo.
Steroidogenic Factor 1 (SF-1) is considered an orphan nuclear receptor that belongs to subfamily 5. It was found to be a regulator of steroidogenic enzyme gene expression. Oxysterols are suggested as its ligands.
It is expressed in all steroidogenic tissues, including the adrenal cortex, testicular Sertoli cells, and Leydig cells, ovarian theca, hypothalamus, and anterior pituitary. SF-1 plays an important role in adrenal and gonadal development.SF-1 is highly valuable marker to determine the adrenocortical origin of an adrenal mass.
Steroidogenic factor-1 (SF-1), functioning as both a nuclear receptor and transcription factor, is a critical regulator of steroidogenesis. SF-1 is recognized as a master regulator of development and functional processes within reproductive and adrenal tissues. Immunohistochemical evaluation of SF-1 expression in testicular tissue is useful in differentiating sex cord-stromal tumors, including Leydig cell, Sertoli cell, and granulosa cell neoplasms, from other tumor types. Furthermore, SF-1 immunodetection serves as a valuable diagnostic tool in distinguishing primary adrenal cortical lesions from histologic mimics such as renal clear cell carcinoma
Signalling from ligand-activated membrane receptor serine/threonine kinases to nuclear targets is mediated by a group of evolutionarily conserved proteins, including DPC4. When ligands bind to receptors of the TGF-? family, they phosphorylate SMAD proteins, specifically SMAD1 and SMAD2. These phosphorylated SMAD proteins then translocate to the nucleus, where they promote transcription. To fulfil this function, receptor-activated SMAD1 and SMAD2 require interaction with the product of deleted in pancreatic carcinoma, locus 4 (DPC4), also known as SMAD4. SMAD4/DPC4 functions as a tumor suppressor, as it is inactivated in over half of pancreatic carcinomas and, to a lesser extent, in other cancers.
Smoothelin is a cytoskeletal protein selectively expressed in fully differentiated, contractile smooth muscle cells (SMCs), serving as a specific marker of terminal SMC differentiation. It is absent in phenotypically related cell types such as myofibroblasts, myoepithelial cells, and striated muscle cells, including skeletal and cardiac muscle. Smoothelin exhibits a distinct filamentous cytoplasmic organization, as demonstrated by confocal laser scanning microscopy and transfection assays, and colocalizes with actin stress fibers. This structural pattern is morphologically and functionally distinct from other cytoskeletal proteins such as desmin and vimentin. Two tissue-specific isoforms of smoothelin have been identified: a 59 kDa isoform localized to visceral SMCs and a 100 kDa isoform specific to vascular SMCs. Expression of smoothelin spans multiple species, as confirmed by mRNA and protein analyses, and its expression is tightly associated with the contractile phenotype of SMCs. The human SMTN gene is encoded by a single-copy locus on chromosome 22q12.3.
The SOX10 protein belongs to the SOX genes family of transcription factors that bind to the minor groove in DNA. They are characterized by a homologous sequence called the HMG-box. SOX10 is known to be involved in regulation of embryonic development and determination of cell fate. It combines with other proteins to form complexes and acts as a transcriptional activator. It is very important for neural crest and peripheral nervous system development. SOX10 plays an important role in melanocytic cell differentiation. It can be used as a sensitive marker for melanoma
SOX10 is a transcription factor belonging to the SRY-related HMG-box (SOX) family, which plays a pivotal role in the regulation of embryogenesis and cell fate specification. Functionally, SOX10 can act as a transcriptional activator, often through the formation of multi-protein complexes. It exhibits nucleocytoplasmic shuttling activity and is critically involved in the development and differentiation of neural crest-derived lineages, including components of the peripheral nervous system. Pathogenic variants in the SOX10 gene have been implicated in neurocristopathies such as Waardenburg-Shah syndrome and Waardenburg-Hirschsprung disease
SOX11 (SRY-related HMG-box transcription factor 11) is a member of the group C subfamily of SOX transcription factors, which are involved in the regulation of embryogenesis and cell lineage specification. The SOX11 protein is believed to function as a transcriptional regulator, likely through the formation of multi-protein complexes. It plays a critical role in the development of the central nervous system and has been implicated in both adult neurogenesis and oncogenesis.
In normal physiology, SOX11 is expressed in the developing human central nervous system, and aberrant expression has been observed in various neoplasms including medulloblastoma, glioma, and malignant gliomas, where it may contribute to tumor progression.
Immunohistochemically, SOX11 demonstrates nuclear localization and is consistently expressed in both cyclin D1-positive and cyclin D1-negative mantle cell lymphomas (MCL). In fact, SOX11 immunostaining is typically more intense and uniform than that of cyclin D1, making it a reliable diagnostic marker. The absence of SOX11 expression in MCL may indicate an indolent clinical subtype. The combination of SOX11 and cyclin D1 immunohistochemistry has shown 100% sensitivity and specificity in the diagnosis of cutaneous mantle cell lymphoma.
Additionally, SOX11 expression has been identified in a limited subset of Burkitt lymphoma, lymphoblastic lymphoma, and T-cell prolymphocytic leukemia, further supporting its relevance in hematologic malignancies.
Recognizes a protein of approximately 47kDa, identified as SOX11. This monoclonal antibody (MAb) is highly specific and does not cross-react with other members of the SOX family. Mantle cell lymphoma (MCL) accounts for 5% to 10% of mature B-cell neoplasms and is an aggressive disease genetically characterized by overexpression of Cyclin D1. Cyclin D1 overexpression is the hallmark of MCL. However, approximately 5% to 10% of MCLs lack Cyclin D1 expression and may be misdiagnosed. Almost all Cyclin D1-positive as well as Cyclin D1-negative MCL show overexpression of SOX11. The detection of this transcription factor is a useful biomarker for identifying true Cyclin D1-negative MCL..
SOX17 (SRY-box transcription factor 17) is a member of the SRY-related HMG-box (high mobility group box) family of transcription factors. It functions as a DNA-binding transcriptional regulator that induces conformational changes in target promoter regions by bending the DNA. SOX17 specifically recognizes and binds to the consensus sequences 5'-AACAAT-3' and 5'-AACAAAG-3'. It modulates gene expression by interacting with the WNT3A signalling cascade and negatively regulates the canonical Wnt pathway through promotion of activated ?-catenin (CTNNB1) degradation. SOX17 is critically involved in early embryogenesis, particularly in cardiac morphogenesis?facilitating proper looping of the embryonic heart tube?and in the specification and development of the definitive gut endoderm. Pathogenic variants in SOX17 have been associated with congenital anomalies such as vesicoureteral reflux
SOX2 is required for stem cell maintenance in the central nervous system, and it also regulates gene expression in the stomach. SOX2 is necessary for regulating multiple transcription factors that affect Oct 3/4 expression. An essential function of SOX2 is to stabilize embryonic stem cells in a pluripotent state by maintaining the requisite level of Oct 3/4 expression. Reportedly, SOX2 is associated with aggressive phenotypes of breast, head and neck, gastric, colorectal, bladder, and small cell lung cancers. However, SOX2 is expressed in a high percentage of lung squamous cell carcinomas and has been shown to be an independent favourable prognostic marker
SOX2 (SRY-box transcription factor 2) is a key regulatory protein belonging to the SOX (SRY-related HMG-box) family of transcription factors. It plays a critical role in maintaining the pluripotency and self-renewal capacity of undifferentiated embryonic stem cells. SOX2 is also essential for the maintenance of neural progenitor populations in the central nervous system and contributes to the regulation of gene expression in tissues such as the gastric epithelium.
Immunohistochemically, SOX2 expression is observed in the fetal brain, where it serves as a marker for multipotent neural stem/progenitor cells. In the context of neoplasia, SOX2 is frequently expressed in a wide spectrum of tumors, including central nervous system teratomas, melanomas, testicular germ cell tumors, cervical carcinomas, lung carcinomas, breast carcinomas with basal-like phenotype, and squamous cell carcinomas of the gastrointestinal tract.
SOX2 is considered a useful diagnostic marker for identifying embryonic carcinoma. In stage I lung adenocarcinomas, elevated SOX2 expression has been identified as an independent prognostic indicator of poor clinical outcome, suggesting its potential utility in risk stratification and post-surgical management
Expression of SS18-SSX fusion protein is the hallmark of Synovial Sarcoma, a type of soft tissue sarcoma that accounts for 5-10% of all soft tissue sarcoma. SS18-SSX is a fusion oncoprotein created during chromosome translocation in which the SS18 gene on chromosome 18 is fused to the SSX1, SSX2, or SSX4 gene on the X chromosome. In normal cells, SS18 subunit and BAF47 subunit bind to the BAF (mSWI/SNF) complex which produces polycomb-mediated repression of SOX-2 and cessation of proliferation. SS18-SSX fusion renders the BAF chromatin remodeling complex aberrant through the addition of SSX to the SS18 subunit and the loss of the BAF47 subunit from the BAF (mSWI/SNF) complex. The altered complexes reverse the polycomb-mediated repression and result in the activation of SOX-2 and uncontrolled proliferation. Diagnosis of Synovial Sarcoma can be challenging due to histologic overlap with a range of other tumors, therefore, IHC is routinely used in differential diagnosis.
SSTRs (for somatostatin receptors) represent a family of G protein-coupled receptors which mediate the diverse biological actions of somatostatin (SST). There are five distinct subtypes of SSTRs that bind two natural ligands, SST-14 and SST-28. SSTR2 gives rise to spliced variants, SSTR2A and 2B. SSTRs share common signaling pathways such as the ability to inhibit adenylyl cyclase via GTP binding proteins.
Some of the subtypes are also coupled to tyrosine phosphatase (SSTR1,2), Ca2+ channels (SSTR2), Na+/H+ exchanger (SSTR1), PLA-2 (SSTR4), and MAP kinase (SSTR4). Individual target cells typically express more than one SSTR subtype and often all five isoforms. Subtypes of SSTR can form functional homo- and heterodimers.
STAT1 (Signal Transducer and Activator of Transcription 1) is a member of the STAT family of transcription factors that mediates cellular responses to extracellular signals. Upon stimulation, STAT1 is phosphorylated by receptor-associated tyrosine kinases, leading to its dimerization and translocation into the nucleus, where it regulates the transcription of target genes.
STAT1 plays a central role in modulating gene expression programs associated with cell growth, apoptosis, immune regulation, and metabolic pathways. It is broadly activated in response to various cytokines, growth factors, and cellular stress signals, contributing to cell viability and host defense mechanisms.
The STAT1 gene is located on chromosome 2, and produces two distinct isoforms through alternative splicing. Among STAT family members, STAT1 exhibits a wide activation profile and is critical for transducing signals from a diverse array of extracellular stimuli
Prostate-Specific Antigen (PSA) is a 33 kDa glycoprotein serine protease predominantly secreted by the luminal epithelial cells of the prostate gland and the periurethral glandular epithelium. PSA demonstrates robust cytoplasmic expression in both benign and malignant prostatic tissues. Immunohistochemical detection of PSA using anti-PSA antibodies serves as a valuable diagnostic tool for confirming prostatic origin in metastatic carcinomas involving non-prostatic sites
STAT6 is a transcription factor in the Jak/STAT signal transduction pathway responsible for mediating IL-4 immune signaling. STAT6 was recently suggested to be a reliable marker to distinguish solitary fibrous tumors from other soft tissue neoplasms. Gene fusions are common in solitary fibrous tumors. By immunohistochemistry, nuclear STAT6 expression can discriminate solitary fibrous tumors from its morphological mimics in the meninges, including meningioma, glioblastoma, gliosarcoma, haemangioblastoma, schwannoma and haemangioma.
Survivin, also known as baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5), is a member of the inhibitor of apoptosis (IAP) protein family. Functionally, survivin suppresses apoptosis through inhibition of caspase activation, thereby contributing to negative regulation of programmed cell death. Survivin expression is markedly elevated in a wide spectrum of human malignancies as well as in fetal tissues, but is absent in terminally differentiated adult cells. Its expression is tightly regulated in a cell cycle?dependent manner, being restricted to the G2/M phase. During mitosis, survivin localizes to the mitotic spindle via interaction with tubulin, suggesting a dual role in apoptosis inhibition and mitotic regulation.
Immunohistochemical studies have demonstrated that survivin expression correlates with tumor progression in several malignancies, including renal cell carcinoma, ovarian carcinoma, hepatocellular carcinoma, prostate carcinoma, and breast carcinoma. However, survivin expression does not consistently predict overall patient survival.
SV40 antibody detects the Simian vacuolating virus 40 or Simian virus 40 (SV40), a polyomavirus that is found in both monkeys and humans. Like other polyomaviruses, SV40 is a DNA virus that has the potential to cause tumors, but most often persists as a latent infection
Synaptophysin, a 38 kD glycoprotein, is the major integral membrane protein of synaptic vesicles. It consists of four transmembrane domains. This protein is present in almost all neurons and neuroendocrine cells throughout the body. This antibody may be useful for the identification of tumors with neural and neuroendocrine differentiation.
Synaptophysin, a 38 kD glycoprotein, is the major integral membrane protein of synaptic vesicles. It consists of four transmembrane domains.
This protein is present in almost all neurons and neuroendocrine cells throughout the body. This antibody may be useful for the identification of tumors with neural and neuroendocrine differentiation. Synaptophysin is currently the most widely used marker for nerve terminals and for differentiating neuroendocrine tumors. Mutations in the gene can result in mental retardation, X-linked 96.