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|Classification and external resources|
Micrograph of endometrioid endometrial adenocarcinoma, the most common form of endometrial cancer. H&E stain.
Endometrial cancer refers to several types of malignancies that arise from the endometrium, or lining, of the uterus. Endometrial cancers are the most common gynecologic cancers in the United States, with over 35,000 women diagnosed each year. The incidence is on a slow rise secondary to the obesity epidemic. The most common subtype, endometrioid adenocarcinoma, typically occurs within a few decades of menopause, is associated with obesity, excessive estrogen exposure, often develops in the setting of endometrial hyperplasia, and presents most often with vaginal bleeding. Endometrial carcinoma is the third most common cause of gynecologic cancer death (behind ovarian and cervical cancer). A total abdominal hysterectomy (surgical removal of the uterus) with bilateral salpingo-oophorectomy is the most common therapeutic approach.
Endometrial cancer may sometimes be referred to as uterine cancer. However, different cancers may develop not only from the endometrium itself but also from other tissues of the uterus, including cervical cancer, sarcoma of the myometrium, and trophoblastic disease.
Most endometrial cancers are carcinomas (usually adenocarcinomas), meaning that they originate from the single layer of epithelial cells that line the endometrium and form the endometrial glands. There are many microscopic subtypes of endometrial carcinoma, including the common endometrioid type, in which the cancer cells grow in patterns reminiscent of normal endometrium, and the far more aggressive papillary serous carcinoma and clear cell endometrial carcinomas. Some authorities have proposed that endometrial carcinomas be classified into two pathogenetic groups:
- Type I: These cancers occur most commonly in pre- and peri-menopausal women, often with a history of unopposed estrogen exposure and/or endometrial hyperplasia. They are often minimally invasive into the underlying uterine wall, are of the low-grade endometrioid type, and carry a good prognosis.
- Type II: These cancers occur in older, post-menopausal women, are more common in African-Americans, are not associated with increased exposure to estrogen, and carry a poorer prognosis. They include:
FIGO grading of Endometrial Carcinoma
G1: Highly differentiated (composed of glands and 5% of lesion is of solid growth pattern). G2: Moderately differentiated ( 6%-50% of lesion composed of solid sheets of cells). G3: Undifferentiated ( > 50% of lesion composed of solid sheets of cells).
In contrast to endometrial carcinomas, the uncommon endometrial stromal sarcomas are cancers that originate in the non-glandular connective tissue of the endometrium. Uterine carcinosarcoma, formerly called Malignant mixed müllerian tumor, is a rare uterine cancer that contains cancerous cells of both glandular and sarcomatous appearance - in this case, the cell of origin is unknown.
Signs and symptoms 
- Vaginal bleeding and/or spotting in postmenopausal women.
- Abnormal uterine bleeding, abnormal menstrual periods.
- Bleeding between normal periods in premenopausal women in women older than 40: extremely long, heavy, or frequent episodes of bleeding (may indicate premalignant changes).
- Anemia, caused by chronic loss of blood. (This may occur if the woman has ignored symptoms of prolonged or frequent abnormal menstrual bleeding.)
- Lower abdominal pain or pelvic cramping.
- Thin white or clear vaginal discharge in postmenopausal women.
Risk factors 
- obesity -
- high levels of estrogen
- endometrial hyperplasia
- polycystic ovary syndrome
- nulliparity (never having carried a pregnancy)
- infertility (inability to become pregnant)
- early menarche (onset of menstruation)
- late menopause (cessation of menstruation)
- endometrial polyps or other benign growths of the uterine lining
- high intake of animal fat
- pelvic radiation therapy
- breast cancer
- ovarian cancer
- anovulatory cycles
- age over 35
- lack of exercise
- heavy daily alcohol consumption (possibly a risk factor) 
Clinical evaluation 
Routine screening of asymptomatic women is not indicated, since the disease is highly curable in its early stages. Results from a pelvic examination are frequently normal, especially in the early stages of disease. Changes in the size, shape or consistency of the uterus and/or its surrounding, supporting structures may exist when the disease is more advanced.
- A Pap smear may be either normal or show abnormal cellular changes. A Pap smear is used to screen for cervical cancer not endometrial cancer.
- Office endometrial biopsy is the traditional diagnostic method. Both endometrial and endocervical material should be sampled.
- If endometrial biopsy does not yield sufficient diagnostic material, a dilation and curettage (D&C) is necessary for diagnosing the cancer.
- Hysteroscopy allows the direct visualization of the uterine cavity and can be used to detect the presence of lesions or tumours. It also permits the doctor to obtain cell samples with minimal damage to the endometrial lining (unlike blind D&C).
- Endometrial biopsy or aspiration may assist the diagnosis.
- Transvaginal ultrasound to evaluate the endometrial thickness in women with postmenopausal bleeding is increasingly being used to evaluate for endometrial cancer.
- Ongoing research suggests that serum p53 antibody may hold value in identifying high-risk endometrial cancer.
Diagnostic test study of S-p53 Ab and agreement study for high-risk endometrial cancer Kappa: 0.70 Sensitivity (%): 64 Specificity(%): 96 PPV: 78 NPV: 92
The histopathology of endometrial cancers is highly diverse. The most common finding is a well-differentiated endometrioid adenocarcinoma, which is composed of numerous, small, crowded glands with varying degrees of nuclear atypia, mitotic activity, and stratification. This often appears on a background of endometrial hyperplasia. Frank adenocarcinoma may be distinguished from atypical hyperplasia by the finding of clear stromal invasion, or "back-to-back" glands which represent nondestructive replacement of the endometrial stroma by the cancer. With progression of the disease, the myometrium is infiltrated. However, other subtypes of endometrial cancer exist and carry a less favorable diagnosis such as the uterine papillary serous carcinoma and the clear cell carcinoma.
Further evaluation 
Patients with newly-diagnosed endometrial cancer do not routinely undergo imaging studies, such as CT scans, to evaluate for extent of disease, since this is of low yield. Preoperative evaluation should include a complete medical history and physical examination, pelvic examination and rectal examination with stool guaiac test, chest X-ray, complete blood count, and blood chemistry tests, including liver function tests. Colonoscopy is recommended if the stool is guaiac positive or the woman has symptoms, due to the etiologic factors common to both endometrial cancer and colon cancer. The tumor marker CA-125 is sometimes checked, since this can predict advanced stage disease. In addition to this, both D&C and Pipelle biopsy curettage give 65-70% positive predictive value. But most important of these is hysteroscopy which gives 90-95% positive predictive value.
The 2010 FIGO staging system is as follows: Carcinoma of the Endometrium
- IA Tumor confined to the uterus, no or < ½ myometrial invasion
- IB Tumor confined to the uterus, > ½ myometrial invasion
- II Tumor involves the uterus and the cervical stroma
- IIIA Tumor invades serosa or adnexa
- IIIB Vaginal and/or parametrial involvement
- IIIC1 Pelvic lymph node involvement
- IIIC2 Para-aortic lymph node involvement, with or without pelvic node involvement
- IVA Tumor invasion bladder mucosa and/or bowel mucosa
- IVB Distant metastases including abdominal metastases and/or inguinal lymph nodes
The primary treatment is surgical. Surgical treatment should consist of, at least, cytologic sampling of the peritoneal fluid, abdominal exploration, palpation and biopsy of suspicious lymph nodes, abdominal hysterectomy, and removal of both ovaries (bilateral salpingo-oophorectomy). Lymphadenectomy, or removal of pelvic and para-aortic lymph nodes, is sometimes performed for tumors that have high risk features, such as pathologic grade 3 serous or clear-cell tumors, invasion of more than 1/2 the myometrium, or extension to the cervix or adnexa. Sometimes, removal of the omentum is also performed.
Women with stage 1 disease who are at increased risk for recurrence and those with stage 2 disease are often offered surgery in combination with radiation therapy. Chemotherapy may be considered in some cases, especially for those with stage 3 and 4 disease. Hormonal therapy with progestins and antiestrogens has been used for the treatment of endometrial stromal sarcomas.
The antibody Herceptin, which is used to treat breast cancers that overexpress the HER2/neu protein, has been tried with some success in a phase II trial in women with uterine papillary serous carcinomas that overexpress HER2/neu.
Complications of treatment 
While endometrial cancers are 40% more common in Caucasian women, an African American woman who is diagnosed with uterine cancer is twice as likely to die (possibly due to the higher frequency of aggressive subtypes in that population, but more probably due to delay in the diagnosis).
Survival rates 
The 5-year survival rates for endometrial adenocarcinoma following appropriate treatment are:
|Stage||5 year survival rate|
It's the most frequent cancer occurring in the female genital tract in the United States and many other Western countries. It appears most frequently between ages of 55 and 65, and uncommon below 40. There are two pictures of this disease, perimenopausal women with estrogen excess and in older women with endometrial atrophy.
See also 
Additional images 
Endometrioid endometrial adenocarcinoma - intermediate magnification. H&E stain.
Uterine papillary serous carcinoma. H&E stain.
- Bokhman JV (1983). "Two pathogenetic types of endometrial carcinoma". Gynecol. Oncol. 15 (1): 10–7. doi:10.1016/0090-8258(83)90111-7. PMID 6822361.
- Richard Cote, Saul Suster, Lawrence Weiss, Noel Weidner (Editor) (2002). Modern Surgical Pathology (2 Volume Set). London: W B Saunders. ISBN 0-7216-7253-1.
- J.C.E. Underwood and S.S. Cross (2009). General and Systemic pathology. London: Elsevier (Churchill Livingstone). ISBN 978-0-443-06889-8.
- Goodman, ET; et al (1997). "Diet, body size, physical activity, and the risk of endometrial cancer.". Cancer Res 57: 5077.
- Friedenreich, CM; Neilson, HK, Lynch, BM (2010 Sep). "State of the epidemiological evidence on physical activity and cancer prevention.". European journal of cancer (Oxford, England : 1990) 46 (14): 2593–604. doi:10.1016/j.ejca.2010.07.028. PMID 20843488.
- "Thirteen studies to date have reported on the relationship between endometrial cancer and alcohol consumption. Only two of these studies have reported that endometrial cancer incidence is associated with consumption of alcohol; all the others have reported either no definite association, or an inverse association." (Six studies showed an inverse association; that is, drinking was associated with a lower risk of endometrial cancer) "…if such an inverse association exists, it appears to be more pronounced in younger, or premenopausal, women." "Our results suggest that only alcohol consumption equivalent to 2 or more drinks per day increases risk of endometrial cancer in postmenopausal women."
- Yamazawa, K; Shimada, H; Hirai, M; Hirashiki, K; Ochiai, T; Ishikura, H; Shozu, M; Isaka, K (2007). "Serum p53 antibody as a diagnostic marker of high-risk endometrial cancer.". American journal of obstetrics and gynecology 197 (5): 505.e1–7. doi:10.1016/j.ajog.2007.04.033. PMID 17980190.
- Dotters, DJ (2000). "Preoperative CA 125 in endometrial cancer: is it useful?". American journal of obstetrics and gynecology 182 (6): 1328–34. doi:10.1067/mob.2000.106251. PMID 10871446.
- Chong, I; Hoskin, PJ (2008). "Vaginal vault brachytherapy as sole postoperative treatment for low-risk endometrial cancer.". Brachytherapy 7 (2): 195–9. doi:10.1016/j.brachy.2008.01.001. PMID 18358790.
-  American Cancer Society - Uterine Sarcomas - Hormonal Therapy (accessed 5-25-07)
- Santin AD, Bellone S, Roman JJ, McKenney JK, Pecorelli S. (2008). "Trastuzumab treatment in patients with advanced or recurrent endometrial carcinoma overexpressing HER2/neu". Int J Gynaecol Obstet 102 (2): 128–31. doi:10.1016/j.ijgo.2008.04.008. PMID 18555254.
- American Cancer Society (2009-10-22). "How Is Endometrial Cancer Staged?". Retrieved 2010-03-09 [Note Stage I definitions in ref differed from those used on Wiki page, so adjusted table labels from 0, IA, IB, to IA, IB, IC matching definitions used here].
- DiCristofano A, Ellenson LH: Endometrial carcinoma. Annual Review of Pathology: Mechanisms of Disease, Vol. 2:57 , 2007. [A comprehensive discussion of pathogenesis.]
- American Cancer Society's Detailed Guide: Endometrial Cancer
- U.S. National Cancer Institute: Endometrial cancer
- NIH Endometrial cancer fact page
- Anatomical pathology images
- MedPix endometrial cancer images