Endometrial Cancer

The following factors may increase the risk of developing uterine cancer:

Age . Uterine cancer occurs most often after age 50. The average age at diagnosis is 60. Uterine cancer is not common in people under age 45.

Obesity . Fat tissue in people who are overweight produces extra estrogen, a hormone that can increase the risk of uterine cancer. This risk increases with increasing body mass index, which is the ratio of a person’s weight to height (BMI). About 70% of uterine cancer cases are linked to obesity.

Race . White women are more likely to develop uterine cancer than women of other races/ethnicities. However, women of color are more likely to be diagnosed with advanced uterine cancer. Women of color and Hispanic women also have a higher risk of developing aggressive tumors.

Heredity . Uterine cancer can run in families where colon cancer is hereditary. Women in families with Lynch syndrome, also called hereditary non-polyposis colorectal cancer (HNPCC), have a higher risk of uterine cancer. It is recommended that all women with endometrial cancer have their tumors tested for Lynch syndrome, even if they do not have a family history of colon cancer or other cancers. The presence of Lynch syndrome has significant implications for women and their family members. About 2% to 5% of women with endometrial cancer have Lynch syndrome.

Type 2 diabetes . A person may have an increased risk of uterine cancer if they have type 2 diabetes, which is often associated with obesity (see above).

Other cancers. People who have had breast, colon, or ovarian cancer may have an increased risk of uterine cancer.

Tamoxifen . People who take the drug tamoxifen to reduce their risk of developing breast cancer or breast cancer recurrence have an increased risk of developing uterine cancer. The benefits of tamoxifen usually outweigh the risk of developing uterine cancer, but anyone prescribed tamoxifen should talk to their doctor about their personal benefits and risks.

Radiation therapy . People who have had previous radiation therapy for another cancer in the pelvic area, which is the lower part of the abdomen between the hip bones, have an increased risk of uterine cancer.

Diet . People who eat foods high in animal fat may have an increased risk of uterine cancer.

Estrogen . Prolonged exposure to estrogen and/or estrogen imbalance.

In addition to a physical examination, the following tests may be used to diagnose uterine cancer:

Pelvic exam . The doctor examines the uterus, vagina, ovaries, and rectum to check for any unusual findings. The Pap test is mainly used to screen for cervical cancer. Sometimes, a Pap test can detect abnormal glandular cells, which are caused by cervical cancer.

Endometrial biopsy . A biopsy is the removal of a small amount of tissue for examination under a microscope. Other tests may suggest that cancer is present, but only a biopsy can make a definitive diagnosis. A pathologist is a doctor who specializes in interpreting laboratory tests and evaluating cell and tissue samples to diagnose the disease.

Dilation and curettage (D&C) . A D&C is a procedure to remove tissue samples from the uterus. A D&C is often done in conjunction with a hysteroscopy so that the doctor can see the lining of the uterus during the procedure.

Transvaginal ultrasound . Ultrasound uses sound waves to create a picture of internal organs. In a transvaginal ultrasound, an ultrasound wand is inserted into the vagina and aimed at the uterus to take pictures. If the endometrium appears very thick, the doctor may decide to perform a biopsy (see above).

Computed tomography (CT or CAT) scan . A CT scan takes pictures of the inside of the body using X-rays taken from different angles. A computer combines these images into a detailed, three-dimensional image that shows any abnormalities or tumors. Sometimes, a special dye called a contrast agent is given before the scan to provide better detail in the image. This dye is usually injected into the patient’s vein, but it can also be given as a pill or liquid to swallow.

Magnetic resonance imaging (MRI) . An MRI uses magnetic fields, not X-rays, to produce detailed images of the body. An MRI can be used to measure the size of a tumor. As with a CT scan, a special dye called contrast may be given intravenously or by mouth before the scan to create a clearer image. An MRI is often used in people with low-grade uterine cancer to see how far the cancer has grown into the wall of the uterus.

Tumor biomarker testing . Your doctor may recommend laboratory tests on a tumor sample to identify specific genes, proteins, and other factors unique to the tumor. This may also be called molecular testing of the tumor. The results of these tests can help determine your treatment options.

People with uterine cancer may experience the following symptoms or signs.

Unusual vaginal bleeding, spotting, or discharge. For premenopausal individuals, this includes menorrhagia, which is unusually heavy or prolonged bleeding, and/or abnormal uterine bleeding.

Abnormal Pap test results (see Diagnosis)

Pain in the pelvic area

The most common symptom of endometrial cancer is abnormal vaginal bleeding, which can range from a watery spotting to a thicker flow that contains more blood. Vaginal bleeding during or after menopause is often a sign of a problem.

Targeted therapy is a treatment that targets specific genes, proteins, or the environment of cancer tissues that contribute to the growth and survival of the cancer. This type of therapy prevents the growth and spread of cancer cells and limits damage to healthy cells.

Not all tumors have the same targets. To find the most effective treatment, your doctor may perform tests to identify the genes, proteins, and other factors in your tumor. This helps doctors better match each patient with the most effective treatment whenever possible. In addition, research studies continue to discover more about specific molecular targets and new treatments that target them.

Targeted therapy for uterine cancer is available in clinical trials and, in some cases, as part of standard treatment plans. Targeted therapy for uterine cancer includes:

Anti-angiogenesis therapy. Anti-angiogenesis therapy focuses on stopping angiogenesis, which is the process of creating new blood vessels. Because a tumor needs the nutrients provided by blood vessels to grow and spread, the goal of anti-angiogenesis therapies is to “starve” the tumor.

Target of rapamycin (mTOR) inhibitors. In endometrial cancer, mutations in a molecular pathway called mTOR are commonly found. People with advanced or recurrent uterine cancer can be treated with a drug that blocks this pathway, such as everolimus. Other drugs that target this pathway are being studied, such as ridaforolimus and temsirolimus, a targeted therapy approved to treat a type of kidney cancer called renal cell carcinoma.

Targeted therapy to treat a rare type of uterine cancer. Serous carcinoma of the uterus is a rare but aggressive type of endometrial cancer. About 30% of these tumors express the HER2 gene. In a phase II clinical trial, researchers found that trastuzumab in combination with chemotherapy was effective in treating this type of tumor. Trastuzumab is a targeted therapy used primarily to treat HER2-positive breast cancer.

Immunotherapy uses the body’s natural defenses to fight cancer, improving your immune system’s ability to attack cancer cells.

Uterine cancers with defective mismatch repair (dMMR) are more sensitive to immunotherapy. The immunotherapy drug pembrolizumab is approved to treat tumors that have microsatellite instability (MSI-high or dMMR), regardless of the tumor’s location in the body. Pembrolizumab can be used to treat uterine tumors if other previous treatments have not worked.

A combination of lenvatinib, a targeted therapy drug, and pembrolizumab, is also approved for the treatment of advanced endometrial cancer. This combination can be used to treat tumors that are not MSI-High or dMMR, have not been controlled by systemic therapy, and cannot be cured by surgery or radiation therapy.

In April 2021, the FDA approved the immunotherapy drug dostarlimab for the treatment of recurrent or advanced endometrial cancer with dMMR that has progressed either during or after completion of platinum-containing chemotherapy.

Endometrial cancer is a clinically heterogeneous disease characterized by a number of different histological subtypes, and its heterogeneity may be related to the accumulation of distinct patterns of genetic alterations, which have prognostic and therapeutic value.

Until recently, endometrial cancer was traditionally treated with surgery and adjuvant therapy depending on clinicopathological risk factors. Genomic analyses in 2013 and subsequent immunohistochemical studies have led to the current molecular classification of high grade and/or high risk cases of this cancer into 4 categories:

1. The category with mutations in the POLE gene (POLEmut), which has a good prognosis and retrospective studies show that omitting adjuvant therapy is safe,
2. The category with abnormal p53 (p53abn), which is associated with increased recurrence, reduced survival and benefit from chemotherapy,
3. The category with a deficiency in the DNA repair mechanism mediated by the MMR system proteins (MMRd) and
4. The category with non-specific molecular profile (NSMP), which may include mutations in the CTNNB1, PTEN genes or expression of the L1CAM marker.

The latter two categories have a moderate prognosis and will likely continue to rely closely on the clinicopathological characteristics of the cancer for receiving adjuvant therapy.

Until recently, endometrial cancer was traditionally treated with surgery and adjuvant therapy depending on clinicopathological risk factors. Genomic analyses in 2013 and subsequent immunohistochemical studies have led to the current molecular classification of high grade and/or high risk cases of this cancer into 4 categories:

1. The category with mutations in the POLE gene (POLEmut), which has a good prognosis and retrospective studies show that omitting adjuvant therapy is safe,
2. The category with abnormal p53 (p53abn), which is associated with increased recurrence, reduced survival and benefit from chemotherapy,
3. The category with a deficiency in the DNA repair mechanism mediated by the MMR system proteins (MMRd) and
4. The non-specific molecular profile (NSMP) category, which may include mutations in the CTNNB1, PTEN genes, or expression of the L1CAM marker. The latter two categories have a moderate prognosis and will likely continue to rely closely on the clinicopathological characteristics of the cancer for adjuvant therapy.

The tests are performed on the surgical specimen (paraffin cubes) or the biopsy material (paraffin cube) from which your histological examination was performed or on the aspiration material (FNAB, EBUS) from which your cytological examination was performed. In our fully integrated Laboratory, the pathologist selects the most appropriate & representative paraffin cube, ensuring that the most appropriate sample will be used for the tests. Qualitative and quantitative parameters are checked.

In case your sample is not already at Microdiagnostics archive, please contact us immediately so that we can arrange for its safe and rapid transport to our laboratory. You will also need to quickly and easily complete the Consent Form.

Most of the time, the sample material we are called upon to handle is small because it has resulted from a minimally invasive method (needle biopsy, fluid aspiration, paraffin block with minimal material).

In our laboratory, Pathologists check in a timely manner whether the material to be examined is sufficient. If so, then a management algorithm is followed, with the aim of achieving the performance of multiple tests on the material (Immunohistochemistry, real-time PCR, NGS) in order to fully check the molecular profile of your tumor (proteins, genes, histological Grading).

In this case, and once sample enrichment manipulations have been exhausted, we contact your clinician to discuss alternative approaches in order to obtain the desired information to select the optimal treatment for you. Some examples:

• Performing an alternative test (e.g. Immunohistochemistry instead of PCR, or choosing Next Generation Sequencing (NGS)
• Performing Immunohistochemistry instead of FISH (Fluorescent In Situ Hybridization) and tubulin
• Possible blood sampling instead of tissue testing (liquid biopsy)
• Possible option to take a new biopsy or puncture

Our team will undertake the quick and safe transport of the sample to our laboratory, please inform us at tel. 2310 232 272.

By cash, bank card, bank deposit, or Online interbank deposit.

One of the primary concerns at Microdiagnostics is the protection of your personal data as well as the strict observance of the conditions of protection of your genetic material and medical results. In full compliance with the General Data Protection Regulation (GDPR), we ensure that any test performed is done with your knowledge and consent and we do not communicate results over the phone.