Diagnosis of endometrial precancers
AssigneesThe Brigham and Women's Hospital, Inc., The Ohio State University
InventorsGeorge L. Mutter, Charis Eng
Life of this patent
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Abstract
The invention disclosed herein describes novel methods for diagnosing endometrial precancers by measuring PTEN expression and offers an immunohistochemical biomarker for premalignant disease.
Claims20
A method for determining the likelihood of a group of endometrial cells or an endometrial gland to become cancerous, comprising
- performing immunohistochemistry on a group of endometrial cells or one or more endometrial glands using PTEN antibody or an antigen-binding fragment thereof and
- determining the binding of the PTEN antibody or antigen-binding fragment thereof to the group of endometrial cells or glands, wherein a reduced amount of PTEN antibody or antigen-binding fragment thereof bound to the group of endometrial cells or glands relative to a control group of cells indicates that the group of endometrial cells or glands has an increased likelihood of becoming cancerous.
A method for monitoring the progression of endometrial precancers, comprising,
- determining the expression of PTEN in endometrial cells or glands by immunohistochemistry of an endometrial tissue sample obtained at a first time using a PTEN antibody or an antigen-binding fragment thereof,
- determining the expression of PTEN in endometrial cells or glands by immunohistochemistry of an endometrial tissue sample obtained at a second time using the PTEN antibody or antigen-binding fragment thereof,
- comparing the expression of PTEN in the endometrial cells or glands at the first time and the second time, wherein reduced expression of PTEN at the second time relative to the first time indicates progression of endometrial precancers to a cancerous stage.
A method for diagnosing endometrial precancer in a subject comprising
- obtaining a biological sample of endometrial tissue or cells from a subject,
- contacting the sample with an endometrial cell marker that specifically binds to endometrial cells,
- contacting the sample with an antibody or antigen-binding fragment thereof that specifically binds PTEN,
- determining specific binding between the antibody or antigen-binding fragment thereof and PTEN in the sample, and
- determining the specific binding between the endometrial cell marker, and agents in the sample.
A method for evaluating the effect of candidate pharmacological compounds on endometrial precancer cell phenotype comprising
- culturing endometrial tissue or cells,
- contacting the cultured endometrial tissue or cells with an antibody or antigen fragment thereof that specifically binds to PTEN,
- determining a first amount of specific binding of the antibody or antigen fragment thereof with the endometrial tissue or cells,
- contacting the cultured endometrial tissue or cells with a candidate pharmacological agent,
- contacting the cultured endometrial tissue or cells with the antibody or antigen-binding fragment thereof,
- determining a second amount of specific binding of the antibody or antigen-binding fragment thereof, with the cultured endometrial tissue or cells, and
- comparing the first and second amounts of specific binding of the antibody or antigen-binding fragment thereof to the tissue or cells, wherein a change in the second amount of specific binding of the antibody or antigen-binding fragment thereof, relative to the first amount of specific binding of the antibody or antigen-binding fragment thereof, indicates the candidate pharmacological compound alters the level of PTEN, wherein a decrease in the relative amount of PTEN indicates the onset of or progression of an endometrial precancer cell phenotype, and where an increase in the relative amount of PTEN indicates the regression of an endometrial precancer cell phenotype.
Dependencies are inferred from the claim text.