Molecular pathology of endometrial cancer

Recent research has improved our understanding of how changes in certain molecules can cause normal endometrial cells to become cancerous. It has been known for several years that damaged or defective DNA (called mutations) can alter important genes that regulate cell growth. If these genes are damaged, out-of-control growth may result in cancer.

Sometimes, endometrial cancer and colon cancer may seem to "run in a family." We now know that some of these families have a higher risk for these cancers because they have an inherited defect in certain genes that normally help repair damage to DNA. If these repair enzymes are not working properly, damage to DNA is more likely to persist and cause cancer, Similar DNA repair defects have also been found in endometrial cancer cells from some patients without an inherited tendency to develop this disease. One of the normal genes responsible for suppressing tumor growth, called PTEN, is often abnormal in endometrial cancers.

Tests for this and other DNA changes may someday help find endometrial cancers early. Endometrial cancers without other tumor suppressor genes (or with inactive ones), such as the retinoblastoma (Rb) gene and the p53 gene, tend to be more likely to come back after initial treatment. Tests for these and other DNA changes may someday be used to help predict how aggressive the cancer might be and to select the best treatment for each woman with this disease. The long-range goal of this field of research is gene therapy that can correct the DNA abnormalities that caused the endometrial cells to become cancerous.

Tumor markers

Molecules released by cancer cells can help detect recurrence of some types of cancer. For example, CA 125 is a useful marker in finding recurrent ovarian cancer. Recent studies find that blood tests for CA 125 may also be helpful in finding recurrent endometrial cancer, before tumor deposits are visible by CT or MRI scans. Measuring CA 125 levels in some patients before surgery may also be helpful if it appears the cancer may have spread. This may be useful in deciding which patients will benefit from surgical staging and which patients might be safely treated by hysterectomy without lymph node sampling.

New treatments

Researchers are examining new drugs, combinations of drugs and "targeted therapies" in patients with advanced endometrial cancer. The use of adjuvant chemotherapy, with or without radiation is also under investigation.