AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Corpus cancer is the most frequently occurring female genital cancer. Approximately 39,000 cases of corpus cancer were predicted to occur in the United States in 2007, making it the fourth most common cancer among women; of these women, approximately 7400 will die from the disease.¹

In developed countries, adenocarcinoma of the endometrium is the most common gynecological cancer; however, in developing countries, it is much less common than carcinoma of the cervix. In the United States in the early part of the 20th century, cancer of the cervix killed more women than any other cancer, but in the ensuing decades, the incidence for that malignancy decreased precipitously. This decrease has been credited to the impact of screening with the Papanicolaou test (Pap smear). In less-developed countries, screening for cervical cancer is performed very infrequently, and therefore, cancer of the cervix is quite prevalent.

Frequency

United States

The latest Surveillance, Epidemiology, and End Results (SEER) data note a total age-adjusted incidence of 24.3 cases per 100,000 people, with the incidence in white women being 26.1 cases per 100,000 persons and the incidence in black women being 19.6 cases per 100,000 persons.¹

Mortality/Morbidity

• Approximately 39,000 cases of corpus cancer were predicted to occur in the United States in 2007, making it the fourth most common cancer among women; of these women, approximately 7400 will die from the disease.¹

Race

• Mortality is higher in black women than in white women, with a mortality ratio of 7.1 deaths per 100,000 persons in black women and only 3.9 deaths per 100,000 persons in white women.

Sex

• Endometrial carcinoma occurs only in females.

Age

• Endometrial adenocarcinoma occurs during the reproductive and menopausal years.
• The median age of persons with this malignancy is early in the seventh decade of life, although most patients are aged 50-59 years. Approximately 5% of women younger than 40 years have adenocarcinoma, and 20-25% of women are diagnosed before menopause.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Because approximately 75% of women with endometrial cancer are postmenopausal, the most common symptom is postmenopausal bleeding.
• • Investigate all bleeding during menopause unless the patient is on cyclic replacement therapy with normally anticipated withdrawal bleeding. The duration or amount (staining vs gross) of bleeding does not make any difference.
  • The fact that only approximately 20% of postmenopausal bleeding is due to cancer is appreciated, but obviously, the diagnosis must be eliminated in these patients.
• Because 25% of endometrial cancers are in patients who are perimenopausal or premenopausal, symptoms suggestive of cancer may be more subtle. The idea that any type of bleeding during the perimenopausal period is probably due to menopause is a common misconception. This irregular bleeding is often ignored by the patient and even health care providers. Remember that the normal bleeding pattern during this time should become lighter and lighter and further and further apart. Heavy frequent menstrual periods or intermenstrual bleeding must be evaluated.

Physical

• Because bleeding usually occurs from the endometrium, pelvic examination findings may be entirely normal, with no gross evidence of disease on the cervix and with a normal-sized uterus.
• • Bleeding leads to an evaluation of the endometrium. In the vast majority of cases, no gross evidence of disease is noted.
  • The uterus may be of normal size upon pelvic examination.
  • Cancer can be present upon cervical evaluation and, less frequently, in the upper vagina or periurethrally. In current practice, occult cervical involvement is very unusual, as is clinically evident metastasis, such as in the vagina.

Causes

Multiple epidemiological risk factors have been identified in patients who have adenocarcinoma of the endometrium.

• Endogenous factors
• • Obesity increases the risk for developing endometrial cancer, and some data suggest that a 2- to 3-fold increase in risk occurs if an individual is more than 50 lb heavier than the ideal weight for that person.
  • Nulliparity also increases risk 2- to 3-fold compared with parity.
  • An individual who has had a late menopause (aged >52 y) also appears to have an increased risk.
• Unopposed estrogen
• • Unopposed estrogen, either as replacement therapy or endogenously produced (eg, granulosa cell tumor, polycystic ovarian disease), increases the risk of endometrial cancer several times.
  • Obesity is known to increase endogenous estrogen because the presence of fat appears to be responsible for the conversion of androstenedione to estrogen compounds at a much higher rate than if fat is not present.
  • Anovulation, which may be secondary to unopposed estrogen, also appears to contribute to this situation.
• Tamoxifen
• • The most widely used anticancer drug is tamoxifen, and this drug has been suggested by some studies to cause an increased incidence of adenocarcinoma of the endometrium. These data were derived from retrospective analyses in which adenocarcinoma of the endometrium was not an end point in multiple prospective randomized studies evaluating the role of tamoxifen in patients with breast cancer.²
  • A case control study using the SEER database indicates that when confounding factors have been corrected, the risk of endometrial cancer does not appear to be increased in patients taking tamoxifen. This study is very reassuring because the potential for an increased number of women taking tamoxifen is becoming apparent, particularly as the prophylactic role of tamoxifen has been recommended for high-risk women.
• Combination oral contraceptives
• • In contrast to tamoxifen, increasing data indicate that the use of combination oral contraceptives (OCs) decreases the risk of developing endometrial cancer.
  • Several studies have noted that women who use OCs at some time have a 0.5 relative risk of developing endometrial cancer compared with women who have never used OCs.
  • This protection occurs in women who have used OCs for at least 12 months, and the protection continues for at least 10 years after OC use. Protection is most notable for nulliparous women.
• Cigarette smoking
• • Smoking apparently decreases the risk of developing endometrial cancer.
  • The effects of smoking are related to body weight. Heavier women who smoke have the greatest reduction in risk.
  • Women who smoke are known to undergo menopause 1-2 years earlier than women who do not smoke.
  • Although smoking apparently reduces the risk of developing early stages of endometrial cancer, this advantage is strongly outweighed by the increased risk of lung cancer and other major health problems associated with smoking.
• Associated medical conditions
• • Some associated medical conditions have been found to increase the incidence of endometrial cancer.
  • Breast, colon, and ovarian cancers are frequently observed in women with endometrial cancer.
  • Data suggest that women who have had breast cancer have a 2- to 3-fold increased risk of subsequently developing endometrial cancer.
  • Women who have hereditary nonpolyposis colon cancer (HNPCC) appear to have a markedly increased risk for developing endometrial cancer.
  • • Women with HNPCC account for only 2-10% of all female cases of colon cancer, but approximately 5% of all endometrial cancers occur in women with this risk factor. These women have a 22-50% lifetime risk of developing endometrial cancer, and the disease tends to occur at a younger age (approximately 15 y earlier). The greatest risk of developing endometrial cancer in women with HNPCC occurs from age 40-60 years, at which time the absolute risk is greater than 1% per y.
    • Currently, no data indicate that annual screening of women with HNPCC will detect endometrial cancer at a sufficiently early stage to improve survival compared with those whose diagnosis is made when symptoms appear. Nevertheless, because of the high risk of endometrial cancer in these individuals and because of the potential life-threatening nature of this disease, HNPCC patients should be so informed and screening is certainly suggested. According to American Cancer Society guidelines, women with HNPCC should be offered screening with an endometrial biopsy by age 35 years.
• Family history: Individuals with a family history of endometrial cancer appear to be at increased risk.
• Phenotype characteristics
• • At one time, a classic phenotypic characteristic was thought to exist for a woman who would develop endometrial cancer. This phenotype included patients who were obese, nulliparous, and anovulatory in many instances. More recently, the existence of 2 pathogenic types of endometrial cancer was appreciated.
  • The first type occurs in women who fall into the classic category. These women are obese and have hyperlipidemia, signs of hyperestrogenism, uterine bleeding, infertility, and late onset of menopause. They may have hyperplasia of the ovary and endometrium. These patients tend to be white, obese, nulliparous, and have well-differentiated superficially invasive cancers that are sensitive to progesterone. They have a very favorable prognosis, and extrauterine disease is unusual in this group of patients. Fortunately, most women with endometrial cancer are in this category.
  • The second type occurs in women who have none of the disease states present in the classic presentation. These individuals tend to have poorly differentiated tumors, deep myometrial invasion, a high degree of metastasis to the lymph nodes and other sites, decreased sensitivity to progestins, and a poor prognosis. These patients tend to be thin, multiparous, and African American.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Bleeding from the lower genital tract can occur from the cervix, vulva, or vagina. If the bleeding is due to neoplasms, gross inspection usually helps identify these lesions. If cervical cytology findings are abnormal and no gross lesions are identified, further evaluation must be performed. Atrophic changes in the vagina may lead to bleeding, particularly postcoital. Bleeding from the uterus may be due to any of the many types of benign lesions (eg, polyps, endometritis) or to hormone replacement therapy.

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Imaging Studies

• Vaginal ultrasonography
• • In the past, the increased use of vaginal ultrasonography to evaluate the endometrial stripe has been reported.
  • Some investigators believe that this should be the first diagnostic procedure because vaginal ultrasonography is less invasive than endometrial biopsy.
  • One of the difficulties with using the endometrial stripe as a criterion for further diagnostic tests (eg, endometrial biopsy) is that several conditions may be present that yield a false reading on the endometrial stripe. This is particularly true in a patient who might have an endometrial polyp, is obese or diabetic, or who has been taking tamoxifen.
• Hydroultrasonography
• • If a thickened endometrium is present, obtain a hydroultrasonogram to make sure a false-positive result is not present. This is accomplished by placing a small volume of saline into the endometrial cavity and then repeating the vaginal ultrasonogram.
  • In many instances in which the original vaginal ultrasonogram shows significant endometrial thickness, an ultrasonogram can help differentiate other pathology from true endometrial thickness.
  • Another problem that arises is that the thickness of the endometrium can vary considerably depending on different factors. The thickness of the endometrium depends on whether or not the patient is obese or diabetic, whether she is perimenopausal or postmenopausal (and for how long), whether she is taking hormone replacement therapy, and whether the therapy includes estrogen alone or estrogen plus progesterone. Currently, no generally accepted guidelines exist for each of these different clinical scenarios.

Procedures

• Endometrial biopsy
• • Although fractional dilatation and curettage was historically the definitive diagnostic procedure to help rule out endometrial cancer, in current practice endometrial biopsy as an office procedure is quick, well tolerated, and quite sensitive for making the diagnosis.
  • If endometrial pathology is not present on biopsy specimens and the patient has no further bleeding, no additional diagnostic tests need to be performed.
  • If the patient continues to be symptomatic, then further evaluation of the endometrial cavity is necessary.
• Hysteroscopically directed biopsy: Another diagnostic procedure that has been advocated by some as an even more accurate way of determining the status of the endometrium is a hysteroscopically directed biopsy; however, studies have shown that when results are compared with the histopathology, both false-positive and false-negatives results may be noted using this technique.
• Dilatation and curettage: The current role of the formal dilatation and curettage is probably very limited because the diagnosis can usually be made in the office.
• Examination with the patient under anesthesia: This may be necessary in patients who are bleeding and have a cervical os that is very stenotic. Anesthesia may be required to perform adequate dilatation for endometrial sampling.

Histologic Findings

Pathological diagnosis is obviously the criterion standard for evaluation of the endometrial cavity. A high index of suspicion must be maintained if a diagnosis of endometrial cancer is considered.

Endometrioid adenocarcinoma is the most common histopathologic subtype. A squamous component, either benign (adenocanthoma) or malignant (adenosquamous), does not affect prognosis, but the grade of the adeno component does affect prognosis. Papillary serous and clear cell histotypes confer a poor prognosis but, fortunately, are uncommon compared with adenocarcinoma. Secretory carcinomas are the least frequently occurring cancers and are associated with a good prognosis.

Staging

• The International Federation of Gynecology and Obstetrics (FIGO) staging system for carcinoma of corpus uteri is as follows:
• • Stage IA - Tumor limited to endometrium
  • Stage IB - Invasion to less than one half the myometrium
  • Stage IC - Invasion to more than one half the myometrium
  • Stage IIA - Endocervical glandular involvement only
  • Stage IIB - Cervical stromal invasion
  • Stage IIIA - Tumor invades serosa and/or adnexa and/or positive peritoneal cytology
  • Stage IIIB - Vaginal metastasis
  • Stage IIIC - Metastases to pelvic and/or para-aortic lymph nodes
  • Stage IVA - Tumor invasion of bladder and/or bowel mucosa
  • Stage IVB - Distant metastases including intra-abdominal and/or inguinal lymph nodes
• Cases of carcinoma of the corpus should be classified (or graded) according to the degree of histologic differentiation. The histopathology and degree of differentiation is as follows:
• • Class G1 - Nonsquamous or nonmorular solid growth pattern of 5% or less
  • Class G2 - Nonsquamous or nonmorular solid growth pattern of 6-50%
  • Class G3 - Nonsquamous or nonmorular solid growth pattern of more than 50%

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

See the Medscape CME course Developments in the Management of Cancers of the Endometrium and Cervix.

Surgical Care

Since 1988, FIGO, whose Gynecologic Oncology Committee was responsible for the staging of gynecological cancer, recommended that corpus cancer be staged surgically. Previously, clinical evaluation was used for staging, and multiple studies noted the inaccuracy of clinical staging compared with surgical pathological findings. Therefore, once the diagnosis of endometrial cancer has been made, routine presurgical evaluation is performed to assess operability.

• Special studies, such as CT scans of the abdomen and pelvis or MRIs, are not routinely performed.
• Once preoperative evaluation, which may include a chest radiograph, ECG, and appropriate blood studies, has been performed and the results are found to be normal, the patient is deemed a surgical candidate. Then, an exploratory laparotomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal cytology, and pelvic and para-aortic lymphadenectomy are performed.
• Obviously, if intraperitoneal disease is identified at the time of surgery, attempts are made at surgical removal.
• Staging is then determined based on surgical pathologic findings (see Staging). Subsequent therapy, if needed, is then determined, depending on the surgical pathological findings of the operative procedure.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to eradicate the carcinoma, to reduce morbidity, and to prevent complications.

Drug Category: Chemotherapeutic agents

Used in the treatment of endometrial cancer. Inhibit cell growth and proliferation.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Complications

• Complications that may occur from therapy include complications that are normally expected from the surgical procedure itself. Because a lymphadenectomy is performed, increased bleeding could develop; however, unique complications from the procedure do not usually occur.
• Postoperative complications can be expected, depending on the preoperative clinical condition of the patient. As noted previously (see Causes), many of these patients have comorbidities such as hypertension, obesity, diabetes, and increased age.
• One postoperative complication that may be somewhat more common is thromboembolism because this is increased in patients who have cancer, are obese, and are older. In current practice, most physicians use some type of prophylaxis, either external pneumatic compression or low-dose heparin.

Prognosis

• Multiple prognostic factors exist for endometrial cancer. These prognostic factors generally are related to surgical pathological findings. As in all cancers, the stage of the disease is the most important prognostic factor. Obviously, the surgical procedure helps determine the stage. Listed below are prognostic factors that may relate specifically to the stage of the disease and, thereby, may affect overall survival.
• • Pathology
    • Most endometrial carcinomas are endometrioid adenocarcinomas.
    • Adenoacanthomas (benign squamous components) and adenosquamous carcinoma (malignant squamous components) make up the next largest category.
    • Clear cell and papillary serous adenocarcinomas represent approximately 10% of all endometrial cancers and are considered to be poor histopathological subtypes. These latter subtypes tend to have deeply invasive myometrial involvement, and they have a propensity for extrauterine spread, even though the myometrium may be superficially involved.
    • Previously, a patient with an adenosquamous carcinoma was thought to have a poor prognostic histotype because of the malignant squamous component.
    • Contemporary data suggest that irrespective of whether a squamous component is present (either benign or malignant), prognosis is related directly to the grade of the adeno component and not the fact that a squamous malignancy is present. If a malignant squamous component is present, a greater tendency exists for a more poorly differentiated adeno component to be present.
  • Histological differentiation
    • The degree of histological differentiation of endometrial cancer has long been accepted as a sensitive indicator of prognosis.
    • Patients with well-differentiated adenocarcinomas tend to have involvement of the endometrium or superficial myometrium, and extrauterine disease is unusual.
    • On the other hand, if a poorly differentiated lesion is present, these cancers tend to be much more aggressive, involving significant myometrial invasion, and often have extrauterine metastasis, either with positive peritoneal cytology, retroperitoneal spread, or involvement of the pelvic and/or para-aortic lymph nodes.
    • Because papillary and clear cell carcinomas are associated with a relatively poor prognosis, these subtypes are not usually graded but are considered in the same category as a poorly differentiated cancer.
  • Myometrial invasion
    • The degree of myometrial invasion continues to be a consistent indication of tumor virulence.
    • As the depth of myometrial invasion increases, the chance of having extrauterine disease is greater.
    • As noted above, grade and depth of invasion, as a generalization, are interrelated. As the grade of the tumor increases, an increase usually occurs in the depth of myometrial invasion; however, exceptions exist in that a grade 1 lesion can have deep myometrial invasion and a grade 3 lesion can be limited to the endometrium.
    • When grade and depth of invasion are evaluated separately, the depth of invasion appears to be a more important prognostic factor than the grade of the tumor.
  • Peritoneal cytology
    • Cytological evaluation of the peritoneum appears to be an important prognostic factor.
    • Although no universal agreement has been reached about the significance of cytological evaluation findings, the vast majority of data in the literature suggest that they represent an independent prognostic factor.
    • Cytological evaluation findings also appear to correlate with other prognostic factors, such as depth of myometrial invasion and lymph node metastasis.
    • The FIGO staging system takes the status of peritoneal cytology into consideration in that if malignant cells are present in the peritoneal cytology without any other evidence of extrauterine disease, the patient is classified as having stage IIIA disease. If ascitic fluid is not present at the time of the exploratory laparotomy, a saline lavage of the pelvis and lower abdomen is performed and the specimen is submitted for cytological evaluation.
  • Lymph node metastasis
    • A considerable number of patients who were thought to have clinical stage I endometrial cancer were, in fact, found to have lymph node metastasis when histopathological evaluation was performed on the lymph nodes.
    • Again, a correlation among multiple prognostic factors has been shown to be present. Patients with poorly differentiated cancers, papillary serous and clear cell carcinomas, deep myometrial invasion, positive peritoneal cytology, or adnexal metastasis tend to have an increased risk of having lymph node metastasis.
    • Subsequent therapy after primary surgery depends on prognostic factors and spread of the disease. If the disease is limited to the uterus, surgery appears to be adequate treatment, with the possible exception of patients who have poorly differentiated deeply invasive myometrium. In these patients, data suggest that, possibly, postoperative irradiation may be of benefit. In patients who have disease outside of the uterus, radiation therapy may be effective; however, this has not been evaluated in a prospective randomized study. Most investigators irradiate the appropriate area if lymph node metastasis is present.
    • In patients with advanced disease (ie, intraperitoneal disease, disease outside of the peritoneal cavity), systemic chemotherapy may be of benefit. Studies suggest that cisplatin and doxorubicin are probably the drugs of choice when systemic chemotherapy is needed.
    • As previously noted, staging is the most important prognostic factor. Using the FIGO surgical staging classification from the recent annual report (worldwide data evaluation), 5-year survival rates of 87%, 76%, 63%, and 37% were noted for stages I, II, III, and IV of the disease, respectively. Because substages exist that take into consideration prognostic factors, 4 of the substages within stage I actually have better than 90% 5-year survival rates.

Patient Education

• For excellent patient education resources, visit eMedicine's Women's Health Center and Cancer and Tumors Center. Also, see eMedicine's patient education articles Vaginal Bleeding and Cervical Cancer.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Ignored irregular postmenopausal bleeding could lead to a delay in diagnosis and treatment, which may impact survival.

Special Concerns

• Multiple new prognostic factors of endometrial cancer are being evaluated and are brought about by newer technology, which allows for molecular biological evaluation. Because these evaluations are new, no general agreement has been reached about their importance.
• • Flow cytometry has been used in ploidy analysis (cellular nuclear DNA content) and to measure the proliferative fraction of tumor cells (S phase).
  • The prognostic factors of the endometrial cancer precursor 1 score (ie, myometrial invasion, DNA ploidy, and mean shortest nuclear axis) have been evaluated, and in at least one study, multivariant analysis was noted to be important prognostically.
  • Several other molecular biological characteristics have been noted to be important prognostically, including HER2/NEU and TP53 gene overexpression.
  • Newer characteristics are being identified almost daily. Obviously, the necessity for standardization is needed before applicability is available and conclusions can be reached. As experience is gained with these factors, they may be the new prognostic factors for endometrial cancer.
• The use of pelvic and para-aortic lymphadenectomy in the management of adenocarcinoma of the endometrium is controversial, as follows:
  
  
  • Whether the procedure aids in diagnosis is not in doubt. The question that has been raised is whether or not it also might be therapeutic. It certainly appears to be therapeutic for other gynecological cancers. Retrospective data by Kilgore and colleagues suggest that lymphadenectomy in endometrial cancer can also be therapeutic.³
  • The number of lymph nodes removed appears therapeutic even if positive nodes are present. In evaluating the SEER data, Chan has noted that patients with positive lymph nodes but few total nodes removed had a worse prognosis than if multiple nodes were removed.⁴
  • When proposed, the FIGO surgical staging classification was questioned as being efficacious by many investigators. However, data suggest that the gynecologic oncology community worldwide has accepted the surgical staging classification. In fact, lymphadenectomies are being performed routinely by these investigators.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Surveillance, Epidemiology, and End Results (SEER) Program. SEER Database: Incidence - SEER 9 Regs Public-Use, Nov 2003 Sub (1973-2001). National Cancer Institute, DCCPS, Surveillance Research Program. Available at http://seer.cancer.gov/.
2. Bernstein L, Deapen D, Cerhan JR, et al. Tamoxifen therapy for breast cancer and endometrial cancer risk. J Natl Cancer Inst. Oct 6 1999;91(19):1654-62. [Medline].
3. Kilgore LC, Partridge EE, Alvarez RD. Adenocarcinoma of the endometrium: survival comparisons of patients with and without pelvic node sampling. Gynecol Oncol. Jan 1995;56(1):29-33. [Medline].
4. Chan JK, Cheung MK, Huh WK, et al. Therapeutic role of lymph node resection in endometrioid corpus cancer: a study of 12,333 patients. Cancer. Oct 15 2006;107(8):1823-30. [Medline].
5. American College of Obstetricians and Gynecologists. Estrogen replacement therapy and endometrial cancer. ACOG Committee Opinion: Committee on Gynecologic Practice Number 126--August 1993. Int J Gynaecol Obstet. Oct 1993;43(1):89. [Medline].
6. Creasman WT. Endometrial cancer: incidence, prognostic factors, diagnosis, and treatment. Semin Oncol. Feb 1997;24(1 Suppl 1):S1-140-S1-50. [Medline].
7. Creasman WT, Kohler MF, Odicino F, et al. Prognosis of papillary serous, clear cell, and grade 3 stage I carcinoma of the endometrium. Gynecol Oncol. Dec 2004;95(3):593-6. [Medline].
8. Creasman WT, Morrow CP, Bundy BN, et al. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer. Oct 15 1987;60(8 Suppl):2035-41. [Medline].
9. DiSaia PJ, Creasman WT. 7th ed. Clinical Gynecologic Oncology. St. Louis, Mo: Mosby; 2007.
10. Ferenczy A, Gelfand M. The biologic significance of cytologic atypia in progestogen-treated endometrial hyperplasia. Am J Obstet Gynecol. Jan 1989;160(1):126-31. [Medline].
11. Goff BA, Kato D, Schmidt RA, et al. Uterine papillary serous carcinoma: patterns of metastatic spread. Gynecol Oncol. Sep 1994;54(3):264-8. [Medline].
12. Kadar N, Malfetano JH, Homesley HD. Determinants of survival of surgically staged patients with endometrial carcinoma histologically confined to the uterus: implications for therapy. Obstet Gynecol. Oct 1992;80(4):655-9. [Medline].
13. Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia. A long-term study of "untreated" hyperplasia in 170 patients. Cancer. Jul 15 1985;56(2):403-12. [Medline].
14. Mariani A, Dowdy SC, Keeney GL, et al. High-risk endometrial cancer subgroups: candidates for target-based adjuvant therapy. Gynecol Oncol. Oct 2004;95(1):120-6. [Medline].
15. Morrow CP, Bundy BN, Kurman RJ, et al. Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol. Jan 1991;40(1):55-65. [Medline].
16. Silverberg SG, Major FJ, Blessing JA, et al. Carcinosarcoma (malignant mixed mesodermal tumor) of the uterus. A Gynecologic Oncology Group pathologic study of 203 cases. Int J Gynecol Pathol. 1990;9(1):1-19. [Medline].
17. Zaino RJ, Kurman R, Herbold D, et al. The significance of squamous differentiation in endometrial carcinoma. Data from a Gynecologic Oncology Group study. Cancer. Nov 15 1991;68(10):2293-302. [Medline].

Article Last Updated: Jul 9, 2007