Endometrial Cancer

Definition

Endometrial cancer is a malignant neoplasm arising from the lining of the uterus (endometrium), most commonly presenting in postmenopausal women. It is often associated with unopposed estrogen exposure and obesity.

Epidemiology

• Most common gynecologic malignancy in developed countries
• Peak incidence: 55–65 years
• Higher incidence in women with obesity, diabetes, or metabolic syndrome
• Majority are diagnosed at early stages due to symptomatic vaginal bleeding
• Endometrioid adenocarcinoma is the most frequent histologic type (~80%), followed by serous and clear cell types

Etiology

• Unopposed estrogen exposure (obesity, estrogen therapy, polycystic ovary syndrome)
• Early menarche, late menopause, nulliparity
• Tamoxifen therapy increases risk
• Genetic syndromes: Lynch syndrome (HNPCC), Cowden syndrome
• Other risk factors: hypertension, diabetes, metabolic syndrome

Pathophysiology

• Estrogen stimulates endometrial proliferation, leading to hyperplasia
• Accumulation of genetic mutations in oncogenes and tumor suppressor genes (PTEN, PIK3CA, KRAS, TP53) leads to malignant transformation
• Tumor invades the myometrium and may extend to cervix, adnexa, and lymph nodes
• Spread: lymphatic (pelvic, para-aortic nodes) or hematogenous (lungs, liver, bone)
• Molecular subtypes: microsatellite instability (MSI), copy-number high (serous-like), copy-number low (endometrioid)