Endometrial Phase or Endometrial Cancer Biomarkers

Abstract

Methods for detecting endometrial diseases or an endometrium phase in a subject are described comprising measuring endometrial markers or polynucleotides encoding the markers in a sample from the subject. The invention also provides localization or imaging methods for endometrial diseases, and kits for carrying out the methods of the invention. The invention also contemplates therapeutic applications for endometrial diseases employing endometrial markers, polynucleotides encoding the markers, and / or binding agents for the markers.

Description

FIELD OF THE INVENTION

[0001] The invention relates to endometrial markers, methods for assessing the status of an endometrial tissue, and methods for the detection, diagnosis, prediction, and therapy of an endometrial disease.BACKGROUND OF THE INVENTION

[0002] Differential tagging with isotopic reagents, such as isotope-coded affinity tags (ICAT) (1) or the more recent variation that uses isobaric tagging reagents, iTRAQ (Applied Biosystems, Foster City, Calif.), followed by multidimensional liquid chromatography (LC) and tandem mass spectrometry (MS / MS) analysis is a powerful methodology in the search of biomarkers for various disease states.

[0003] Endometrial carcinoma (EmCa), a cancer of the lining of the uterus, is the fourth most common cancer in Canadian women (4). Current methods of diagnosis rely on invasive techniques—biopsy and curettage—and no screening is available. A panel of biomarkers that helps in early diagnosis would, therefore, be useful, especially for highrisks grou...

Examples

example 1

Experimental Procedures

Samples and Reagents

[0401]Endometrial tissues were retrieved from an in-house, dedicated, research endometrial-tissue bank. With patient consent, samples from hysterectomy specimens had been flash-frozen in liquid nitrogen within 20 minutes of devitalizing. The patient consent forms and tissue-banking procedures were approved by the Research Ethics Boards of York University, Mount Sinai Hospital, University Health Network, and North York General Hospital. These frozen samples were sectioned and stored at −80° C. The histologic diagnosis for each sample was confirmed using microscopic examination of a hematoxylin and eosin-stained frozen section of each research tissue block. The tissue from the mirror face of the histologic section was then washed three times in approximately 1 mL of phosphate-buffered saline (PBS) with a cocktail of protease inhibitors as described previously (1 mM AEBSF, 10 μM leupeptin, 1 μg / mL aprotinin, and 1 μM pepstatin) (3). The washed...

FIELD OF THE INVENTION

[0001] The invention relates to endometrial markers, methods for assessing the status of an endometrial tissue, and methods for the detection, diagnosis, prediction, and therapy of an endometrial disease.BACKGROUND OF THE INVENTION

[0002] Differential tagging with isotopic reagents, such as isotope-coded affinity tags (ICAT) (1) or the more recent variation that uses isobaric tagging reagents, iTRAQ (Applied Biosystems, Foster City, Calif.), followed by multidimensional liquid chromatography (LC) and tandem mass spectrometry (MS / MS) analysis is a powerful methodology in the search of biomarkers for various disease states.

[0003] Endometrial carcinoma (EmCa), a cancer of the lining of the uterus, is the fourth most common cancer in Canadian women (4). Current methods of diagnosis rely on invasive techniques—biopsy and curettage—and no screening is available. A panel of biomarkers that helps in early diagnosis would, therefore, be useful, especially for highrisks grou...

Examples

example 1

Experimental Procedures

Samples and Reagents

[0401]Endometrial tissues were retrieved from an in-house, dedicated, research endometrial-tissue bank. With patient consent, samples from hysterectomy specimens had been flash-frozen in liquid nitrogen within 20 minutes of devitalizing. The patient consent forms and tissue-banking procedures were approved by the Research Ethics Boards of York University, Mount Sinai Hospital, University Health Network, and North York General Hospital. These frozen samples were sectioned and stored at −80° C. The histologic diagnosis for each sample was confirmed using microscopic examination of a hematoxylin and eosin-stained frozen section of each research tissue block. The tissue from the mirror face of the histologic section was then washed three times in approximately 1 mL of phosphate-buffered saline (PBS) with a cocktail of protease inhibitors as described previously (1 mM AEBSF, 10 μM leupeptin, 1 μg / mL aprotinin, and 1 μM pepstatin) (3). The washed...

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