Cancer Diagnostics Solutions
Recognizes a glycoprotein of ~200kDa, identified as carbonic anhydrase IX (CAIX/gp200). Its epitope resides in the carbohydrate domain of gp200. It shows no significant cross-reactivity with other carbohydrate determinants, such as the Lewis blood group antigens, epithelial membrane antigen, HMFG, and AB blood group antigens. In normal kidney, gp200 is localized along the brush border of the pars convoluta and pars recta segments of the proximal tubule, as well as focally along the luminal surface of Bowman's capsule adjoining the outgoing proximal tubule. Reportedly, gp200 is expressed by 93% of primary and 84% of metastatic renal cell carcinomas. This MAb may be useful in the investigations of carcinomas of proximal nephrogenic differentiation especially those showing tubular differentiation.
In normal renal tissue, gp200 is localized along the brush border of both the pars convolute and pars recta segments of the proximal tubule, as well as focally along the luminal surface of Bowman?s capsule adjacent to the emerging proximal tubule. Among other examined normal tissues, gp200 expression is observed along the luminal surfaces of breast lobules and ducts, the luminal surface of the epididymal tubule epithelium, within the cytoplasm of parathyroid chief cells, and focally within the colloid of thyroid follicles. No expression or cross-reactivity is detected in 31 other normal tissue types. Notably, gp200 is expressed in 93% of primary and 84% of metastatic renal cell carcinomas. The monoclonal antibody 66.4.C2 may thus serve as a valuable tool for identifying carcinomas exhibiting proximal nephron differentiation, particularly those with tubular epithelial features.
The retinoblastoma protein (Rb) is a critical tumor suppressor that is frequently inactivated in a wide spectrum of malignancies. Its principal role is the regulation of cell-cycle progression, where it restricts entry into the S phase by controlling the G1 S checkpoint, thereby preventing inappropriate proliferation and replication of damaged DNA. Oncogenic viral proteins, such as those encoded by high-risk human papillomaviruses, SV40, or adenoviruses, can bind to and functionally inactivate Rb, disrupting cell-cycle control and promoting oncogenesis. Antibodies to Rb may influence transcriptional regulation, and loss of Rb activity results in deregulated cellular proliferation. Genetic alterations of the Rb gene have been associated with diverse cancers, including those of the breast, colon, prostate, kidney, and nasopharynx, as well as hematologic malignancies such as leukemia
ROS1, an orphan receptor tyrosine kinase of the insulin receptor family, was initially identified as a homolog of v-ros from the UR2 sarcoma virus. ROS1 consists of a large extracellular domain that is composed of six fibronectin repeats, a transmembrane domain, and an intracellular kinase domain. While the function of ROS1 is undefined, it has been shown to play an important role in differentiation of epididymal epithelium.
The first oncogenic fusion of ROS1, FIG-ROS1, was initially identified by research studies in glioblastoma. Investigators have found additional oncogenic ROS1 fusion proteins in NSCLC (at a frequency of ~1.6%), where the ROS1 kinase domain is fused to the amino-terminal region of a number of different proteins, including CD74 and SLC34A2