Endometrial Cancer: Causes, Staging, and Treatment

Introduction

Cancer occurs when certain cells in the body grow uncontrollably. Cancer that begins in the uterus is referred to as uterine cancer. There are two categories of uterine cancer: endometrial cancer, the most common cancer of the uterus, and uterine sarcoma, a rare form found in the muscles or other uterine tissues. Every woman who has a uterus is at risk of uterine cancer. The risk, however, increases with age and is most common among women who have undergone or are going through menopause.

Endometrial cancer is the most common type of uterine cancer, and it originates in the womb. It begins in the layer of cells forming the uterine lining, also called the endometrium. Because endometrial cancer is the most prevalent form, the terms "endometrial cancer" and "uterine cancer" are sometimes used interchangeably. It is often detected at an early stage because of its primary symptom — abnormal vaginal bleeding — which enables doctors to discover it before it progresses significantly. When caught early, surgical removal of the uterus can be curative. Other associated symptoms include pelvic pain, difficulty urinating, and pain during intercourse.

Epidemiology and Risk Factors

Endometrial cancer is most frequently associated with older women, typically those above 50 years of age. Research statistics indicate that approximately 90 percent of all women diagnosed with endometrial cancer are at least fifty years old, with a median diagnosis age of 63 years. Geographically, this cancer is most common among women in the United Kingdom and is more prevalent in Western countries than in Asia, South America, or Africa, though its incidence is increasing in Asia.

Several risk factors increase a woman's susceptibility to endometrial cancer. These include hormonal imbalances — specifically, changes in the balance of hormones produced by the ovaries — and taking hormone therapy containing estrogen without progesterone after menopause. Age is itself a significant risk factor, as the disease disproportionately affects older and perimenopausal women. Women who began menstruating before age twelve, and therefore experienced longer cumulative periods of menstruation, are also at elevated risk. Women who have never been pregnant face a higher risk than those who have had at least one pregnancy. Additional risk factors include diabetes, hypertension, and obesity.

Pathobiology and Molecular Basis

Endometrial cancer most frequently originates in the corpus or the lower uterine segment. In low-volume cancers, there is often no evidence of residual disease after curettage. Localized cancer typically manifests as circular polypoid expansile masses that are often hemorrhagic and friable. Diffuse endometrial involvement may also display an exophytic visible component, with hemorrhaging and necrosis observable. Foci of myometrium invasion appear as well-demarcated gray-white areas that are lighter than the surrounding myometrial tissue.

Recent studies have demonstrated that mutations occur in microsatellite sequences in some endometrial cancers. Overexpression of the HER-2/neu oncogene is observed in approximately 10 percent of endometrial cancer cases and has been associated with poor survival outcomes. Additionally, receptor tyrosine kinases have been found to occur in certain cases. Microsatellite instability in hereditary nonpolyposis colorectal cancer has been shown to result from mutations or genetic alterations in DNA repair genes, and researchers are investigating whether similar mutations are present in endometrial cancer. While several molecular mutations have been identified, the molecular basis of endometrial cancer as a whole is not yet fully understood.