Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
2000-09-01
2001-05-08
Campbell, Eggerton A. (Department: 1656)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C435S007230
Reexamination Certificate
active
06228596
ABSTRACT:
FIELD OF THE INVENTION
This invention relates, in part, to a newly developed assay for diagnosing cancers, particularly endometrial and uterine cancer.
BACKGROUND OF THE INVENTION
Endometrial cancer occurs at a rate of approximately 44,500 new cases per year with approximately 10,000 deaths per year. If diagnosed and treated early, when the cancer is still confined to the endometrium, cure can be achieved in approximately 95% of the cases by hysterectomy. Pap smears can show endometrial cancers but are effective in only 50% of the cases. For the remainder, abnormal vaginal bleeding is typically the first clinical sign of endometrial cancer. There is a great need for sensitive methods for the detection of organ-confined endometrial cancer.
Sarcoma of the uterus, a very rare kind of cancer in women, is a disease in which cancer (malignant) cells start growing in the muscles or other supporting tissues of the uterus. Sarcoma of the uterus is different from cancer of the endometrium, a disease in which cancer cells start growing in the lining of the uterus. Women who have received therapy with high-dose x-rays (external beam radiation therapy) to their pelvis are at a higher risk to develop sarcoma of the uterus. These x-rays are sometimes given to women to stop bleeding from the uterus. Like most cancers, sarcoma of the uterus is best treated when it is found (diagnosed) early. Sarcoma of the uterus usually begins after menopause.
When a patient has signs of such cancer, the doctor will do certain tests to check for cancer, usually beginning with an internal (pelvic) exam. During the exam, the doctor will feel for any lumps or changes in the shapes of the pelvic organs. The doctor may then do a Pap test. Because sarcoma of the uterus begins inside, this cancer will not usually show up on the Pap test. The doctor may also do a dilation and curettage (D & C) by stretching the cervix and inserting a small, spoon-shaped instrument into the uterus to remove pieces of the lining of the uterus. This tissue is then checked under a microscope for cancer cells.
Prognosis (chance of recovery) and choice of treatment depend on the stage of the sarcoma (whether it is just in the uterus or has spread to other places), how fast tumor cells are growing, and the general state of the patient's health.
As noted, treatment decisions for an individual are linked to the stage of such cancer present in that individual. However, current endometrial and uterine cancer staging methods are limited and some such cancers initially staged as not metastatic are, in fact, metastatic. Discovery of metastasis is significant because patients with metastatic cancers have a poorer prognosis and require significantly different therapy than those with localized cancers.
Accordingly, not only is there a need for more sensitive methods of diagnosing these cancers, but there is also a great need for sensitive methods for staging of an endometrial or uterine cancer in a human to determine whether or not such cancer has metastasized and for monitoring the progress of such cancer in a human which has not metastasized for the onset of metastasis.
Steroid binding proteins, including uteroglobin and CC10, are a class of proteins which bind steroids along with methylsulfonyl metabolites of polychlorinated biphenyls. The exact function of members of this class of proteins is uncertain. Uteroglobin has been shown to inhibit PLA2 mediated responses.
Gene and gene products useful in the present invention display homology to uteroglobin and CC10, show elevated expression of mRNA in endometrial cancer samples and are expressed in mammary tissue. These gene and gene products are described in published patent application WO 97/34997 entitled Human Endometrial Specific Steroid Binding Factors I, II and III which is incorporated herein by reference. The genes and their encoded products are referred to herein as Human Endometrial Specific Steroid-Binding Factor I (hESF I) which corresponds to Human Endometrial Specific Steroid-Binding Factor I (hESF I) published in WO 97/34997. WO 97/34997 teaches that detection of mutated forms of hESF I, II, and III associated with a dysfunction will provide a diagnostic tool that can add to and define diagnosis of a disease or susceptibility of a disease which result from under-expression, over-expression or altered expression of hESF-I, II and II. For example, it is suggested that detection of a mutated gene may be indicative of a susceptibility to inherited asthma or endometrial cancer. WO 97/34997 also discloses a diagnostic assay for detection of over-expression or under-expression of hESF I, II and III protein for use in detection of the presence of neoplasia.
It has now been found that hESF I is useful as cancer marker for diagnosing endometrial and uterine cancer.
SUMMARY OF THE INVENTION
Toward these ends, and others, it is an object of the present invention to provide a method for detecting the expression of the cancer marker hESF I in a patient which comprises taking a sample derived from a patient and detecting in the sample a nucleic acid sequence encoding hESF I or a protein product encoded by a hESF I nucleic acid sequence.
Another object of the present invention is to provide a diagnostic method for detecting the presence of endometrial cancer and/or uterine cancer in a patient suspected of suffering from endometrial cancer and/or uterine cancer which comprises measuring levels of hESF I polypeptide in cells, tissues or bodily fluids obtained from a patient suspected of suffering from endometrial and/or uterine cancer; and comparing the measured levels of hESF I polypeptide with levels of hESF I in normal cells, tissues or bodily fluids, wherein an increase in hESF I polypeptide levels in the patient versus levels of hESF I polypeptide in normal cells, tissues or bodily fluids is indicative of endometrial cancer and/or uterine cancer.
Another object of the present invention is to provide a diagnostic method for detecting the presence of endometrial cancer and/or uterine cancer in a patient suspected of suffering from endometrial and/or uterine cancer which comprises measuring transcription levels of hESF I in cells, tissues or bodily fluids of a patient suspected of suffering from endometrial and/or uterine cancer; and comparing the measured transcription levels of hESF I with hESF I transcription levels in normal cells, tissues or bodily fluids, wherein an increase in hESF I transcription levels in the patient versus normal hESF I transcription levels is associated with endometrial cancer and/or uterine cancer.
Another object of the present invention is to provide a method of monitoring endometrial and/or uterine cancer in a patient which has not metastasized for the onset of metastasis which comprises identifying a patient suffering from endometrial cancer and/or uterine cancer that is not known to have metastasized; measuring hESF I levels in a sample of bodily fluid from said patient; and comparing the measured hESF I levels in said patient with levels of hESF I in the same bodily fluid type from a normal control sample, wherein an increase in measured hESF I levels in the patient versus hESF levels in the normal control sample is associated with a cancer which has metastasized.
Yet another object of the present invention is to provide a method of monitoring the stage of endometrial cancer and/or uterine cancer in a patient suffering from endometrial cancer or uterine cancer which comprises identifying a patient suffering from endometrial cancer and/or uterine cancer; determining hESF I levels in a sample of bodily fluid from said patient to establish a baseline hESF I level for said patient; measuring hESF I levels in samples of the same bodily fluid from said patient at subsequent time periods; and comparing the measured hESF I levels with the baseline hESF I levels, wherein an increase in measured hESF I levels in the patient versus baseline hESF I levels in the patient is associated with a cancer which is progressing and a decrease in measured hESF I levels versus baseline
Burczak John D.
Macina Roberto A.
Campbell Eggerton A.
diaDexus, Inc.
Licata & Tyrrell P.C.
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