Assay to measure midkine or pleiotrophin level for diagnosing a growth
Inventors
Baron, Jeffrey • Jee, Youn Hee
Assignees
US Department of Health and Human Services
Publication Number
US-9664682-B2
Publication Date
2017-05-30
Expiration Date
2033-11-15
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Abstract
The invention provides methods and kits for diagnosing a growth in a subject by providing a sample of a growth taken from a subject, determining the level of midkine or pleiotrophin in the sample by an immunoassay, and comparing the level of midkine or pleiotrophin determined from the sample with a control. An increased level of midkine or pleiotrophin in the sample as compared to the control is diagnostic of a malignant growth, whereas an equivalent or decreased level of midkine or pleiotrophin in the sample as compared to the control is diagnostic of a benign growth. Growth refers to, for example, papillary thyroid cancer (PTC).
Core Innovation
The invention provides methods and kits for diagnosing a growth in a subject by determining the level of midkine or pleiotrophin present in a sample of the growth using an immunoassay and comparing the level to a control. An increased level of midkine or pleiotrophin in the sample as compared to the control is diagnostic of a malignant growth, whereas an equivalent or decreased level is diagnostic of a benign growth. The invention includes the use of antibodies specific to midkine or pleiotrophin and immunoassays such as sandwich ELISA for the detection.
The problem being solved is the need for more reliable, less invasive methods of cancer detection. Current diagnostic approaches often involve invasive procedures like surgical biopsy or less reliable methods like needle biopsies. There is a demand for improved methods, compositions, and kits that can detect midkine or pleiotrophin expression with high sensitivity to aid in diagnosis and prognosis of proliferative disorders, such as cancer.
Claims Coverage
The patent describes one independent claim encompassing a method for diagnosing and treating a growth in a subject using immunoassays to determine the pleiotrophin to thyroglobulin ratio and performing treatment based on diagnosis.
Method of diagnosing growth using pleiotrophin to thyroglobulin ratio
A method comprising: providing a sample of a growth from thyroid tissue; analyzing the sample via immunoassays to determine pleiotrophin and thyroglobulin protein concentrations; calculating the ratio of pleiotrophin to thyroglobulin (PTN/Tg); comparing this ratio to a control; diagnosing the growth as malignant if the PTN/Tg ratio is increased compared to the control; and performing thyroidectomy on the subject based on the diagnosis, where the control ratio corresponds to that in a benign growth.
Use of immunoassay with specific antibodies and polymer to increase sensitivity
The immunoassay for pleiotrophin detection is preferably a sandwich ELISA using an antibody specific to human pleiotrophin protein, which may be conjugated to a label such as biotin or enzymes. The antibody solution can include a polymer, notably poly-L-lysine at a concentration of about 10 µg/mL, to increase sensitivity of detection.
The claims focus on a diagnostic and treatment method for thyroid growths based on immunoassay determination of pleiotrophin to thyroglobulin ratios, employing specific antibodies possibly in conjunction with polymers like poly-L-lysine to enhance assay sensitivity and guiding surgical treatment decisions.
Stated Advantages
High sensitivity of the midkine assay allowing detection in small samples such as fine needle aspirates.
Increased assay sensitivity by including polymers like poly-L-lysine during antigen binding, which enhances antibody affinity or avidity and reduces non-specific binding.
Ability to differentiate benign from malignant growths based on midkine or pleiotrophin levels, enabling less invasive, reliable cancer diagnostics.
Documented Applications
Diagnosing thyroid nodules, particularly differentiating benign thyroid nodules from papillary thyroid cancer using midkine or pleiotrophin levels in fine needle aspirate washout samples.
Diagnosing other types of cancers and growths including but not limited to acute lymphoblastic leukemia, pancreatic carcinoma, colon carcinoma, melanoma, and various solid and hematologic tumors.
Use of the method and kits in conjunction with other diagnostic methods such as histological or cytological examination to improve diagnostic accuracy and reduce invasive procedures.
Using the levels of midkine or pleiotrophin to assess grade of malignancy, predict prognosis, treatment response, and guide treatment choices for a growth.
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