General Information
Note: Separate PDQ summaries on Uterine Sarcoma Treatment, Endometrial Cancer Screening, and Endometrial Cancer Prevention are also available.
Note: Estimated new cases and deaths from endometrial (uterine corpus) cancer in the United States in 2008:[1]
- New cases: 40,100.
- Deaths: 7,470.
Cancer of the endometrium is the most common gynecologic malignancy and
accounts for 6% of all cancers in women. It is a highly curable tumor. To
detect endometrial cancer, a technique that directly samples the endometrial
tissue is mandatory. The Pap smear is not reliable as a screening procedure in
endometrial cancer, though a retrospective study found a strong correlation
between positive cervical cytology and high-risk disease (i.e., high-grade
tumor and deep myometrial invasion) [2] as well as an increased risk of nodal
disease.[3] The degree of tumor differentiation has an important impact on the
natural history of this disease and on treatment selection. An increased
incidence of endometrial cancer has been found in association with prolonged,
unopposed estrogen exposure.[4,5] In contrast, combined estrogen and
progesterone therapy prevents the increase in risk of endometrial cancer
associated with unopposed estrogen use.[6,7] In some patients, an antecedent
history of complex hyperplasia with atypia can be demonstrated. An increased
incidence of endometrial cancer has also been found in association with
tamoxifen treatment of breast cancer (NSABP B-14), perhaps related to the estrogenic effect
of tamoxifen on the endometrium.[8,9] Because of this increase, patients on
tamoxifen should have follow-up pelvic examinations and should be examined if
there is any abnormal uterine bleeding.
The pattern of spread is partially dependent on the degree of cellular
differentiation. Well-differentiated tumors tend to limit their spread to the
surface of the endometrium; myometrial extension is less common. In patients
with poorly differentiated tumors, myometrial invasion occurs much more
frequently. Myometrial invasion is frequently a harbinger of lymph node
involvement and distant metastases and is often independent of the degree of
differentiation.[10,11] Metastatic spread occurs in a characteristic pattern.
Spread to the pelvic and para-aortic nodes is common. Distant metastases can
occur and most commonly involve the lungs, inguinal and supraclavicular nodes,
liver, bones, brain, and vagina.
Another factor found to correlate with extrauterine and nodal spread of tumor
is involvement of the capillary-lymphatic space on histopathologic
examination.[12] Three prognostic groupings of clinical stage I disease become
possible by careful operative staging. Patients with grade 1 tumors involving
only endometrium and no evidence of intraperitoneal disease (i.e., adnexal
spread or positive washings) have a low risk (<5%) of nodal involvement.[13]
Patients with grade 2 or 3 tumors and invasion of less than 50% of the
myometrium and no intraperitoneal disease have a 5% to 9% incidence of pelvic
node involvement and a 4% incidence of positive para-aortic nodes. Patients
with deep muscle invasion and high-grade tumors and/or intraperitoneal disease
have a significant risk of nodal spread, 20% to 60% to pelvic nodes and 10% to
30% to para-aortic nodes. One study was directed specifically at stage I,
grade 1 carcinomas of favorable histologic type. The authors identified four
statistically significant adverse prognostic factors: myometrial invasion,
vascular invasion, eight or more mitoses per ten high-power fields, and an absence
of progesterone receptors.[14]
Another group identified aneuploidy and a high S-phase fraction as predictive
of poor prognosis.[15] A Gynecologic Oncology Group study related
surgical-pathologic parameters and postoperative treatment to recurrence-free
interval and recurrence site. For patients without extrauterine spread, the
greatest determinants of recurrence were grade 3 histology and deep myometrial
invasion. In this study, the frequency of recurrence was greatly increased
with positive pelvic nodes, adnexal metastasis, positive peritoneal cytology,
capillary space involvement, involvement of the isthmus or cervix, and,
particularly, positive para-aortic nodes (includes all grades and depth of
invasion). Of the cases with aortic node metastases, 98% were
in patients with positive pelvic nodes, intra-abdominal metastases, or tumor
invasion of the outer 33% of the myometrium.[16,17]
When the only evidence of extrauterine spread is positive peritoneal cytology,
the influence on outcome is unclear. The value of therapy directed at this
cytologic finding is not well founded.[18-23] The preponderance of evidence,
however, would suggest that other extrauterine disease must be present before
additional postoperative therapy is considered.
One report found progesterone receptor levels to be the single most important
prognostic indicator of 3-year survival in clinical stage I and II disease.
Patients with progesterone receptor levels higher than 100 had a 3-year
disease-free survival of 93% compared with 36% for a level lower than 100. Only
cervical involvement and peritoneal cytology were significant prognostic
variables after adjusting for progesterone receptor levels.[24] Other reports
confirm the importance of hormone receptor status as an independent prognostic
factor.[25] Additionally, immunohistochemical staining of paraffin-embedded
tissue for both estrogen and progesterone receptors has been shown to correlate
with International Federation of Gynecology and Obstetrics grade as well
as survival.[26-28] On the basis of these data, progesterone and estrogen
receptors, assessed either by biochemical or immunohistochemical methods,
should be included, when possible, in the evaluation of stage I and II
patients. Oncogene expression, DNA ploidy, and the fraction of cells in
S-phase have also been found to be prognostic indicators of clinical
outcome.[28] For example, overexpression of the Her-2/neu oncogene has been
associated with a poor overall prognosis.[29] A general review of prognostic
factors has been published.[30]
References
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DuBeshter B, Warshal DP, Angel C, et al.: Endometrial carcinoma: the relevance of cervical cytology. Obstet Gynecol 77 (3): 458-62, 1991.
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Larson DM, Johnson KK, Reyes CN Jr, et al.: Prognostic significance of malignant cervical cytology in patients with endometrial cancer. Obstet Gynecol 84 (3): 399-403, 1994.
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Ziel HK, Finkle WD: Increased risk of endometrial carcinoma among users of conjugated estrogens. N Engl J Med 293 (23): 1167-70, 1975.
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Jick SS, Walker AM, Jick H: Estrogens, progesterone, and endometrial cancer. Epidemiology 4 (1): 20-4, 1993.
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van Leeuwen FE, Benraadt J, Coebergh JW, et al.: Risk of endometrial cancer after tamoxifen treatment of breast cancer. Lancet 343 (8895): 448-52, 1994.
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Fisher B, Costantino JP, Redmond CK, et al.: Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. J Natl Cancer Inst 86 (7): 527-37, 1994.
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Hendrickson M, Ross J, Eifel PJ, et al.: Adenocarcinoma of the endometrium: analysis of 256 cases with carcinoma limited to the uterine corpus. Pathology review and analysis of prognostic variables. Gynecol Oncol 13 (3): 373-92, 1982.
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Nori D, Hilaris BS, Tome M, et al.: Combined surgery and radiation in endometrial carcinoma: an analysis of prognostic factors. Int J Radiat Oncol Biol Phys 13 (4): 489-97, 1987.
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Hanson MB, van Nagell JR Jr, Powell DE, et al.: The prognostic significance of lymph-vascular space invasion in stage I endometrial cancer. Cancer 55 (8): 1753-7, 1985.
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Takeshima N, Hirai Y, Tanaka N, et al.: Pelvic lymph node metastasis in endometrial cancer with no myometrial invasion. Obstet Gynecol 88 (2): 280-2, 1996.
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Tornos C, Silva EG, el-Naggar A, et al.: Aggressive stage I grade 1 endometrial carcinoma. Cancer 70 (4): 790-8, 1992.
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Friberg LG, Norén H, Delle U: Prognostic value of DNA ploidy and S-phase fraction in endometrial cancer stage I and II: a prospective 5-year survival study. Gynecol Oncol 53 (1): 64-9, 1994.
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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 40 (1): 55-65, 1991.
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Lanciano RM, Corn BW, Schultz DJ, et al.: The justification for a surgical staging system in endometrial carcinoma. Radiother Oncol 28 (3): 189-96, 1993.
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Ambros RA, Kurman RJ: Combined assessment of vascular and myometrial invasion as a model to predict prognosis in stage I endometrioid adenocarcinoma of the uterine corpus. Cancer 69 (6): 1424-31, 1992.
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Turner DA, Gershenson DM, Atkinson N, et al.: The prognostic significance of peritoneal cytology for stage I endometrial cancer. Obstet Gynecol 74 (5): 775-80, 1989.
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Piver MS, Recio FO, Baker TR, et al.: A prospective trial of progesterone therapy for malignant peritoneal cytology in patients with endometrial carcinoma. Gynecol Oncol 47 (3): 373-6, 1992.
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Kadar N, Homesley HD, Malfetano JH: Positive peritoneal cytology is an adverse factor in endometrial carcinoma only if there is other evidence of extrauterine disease. Gynecol Oncol 46 (2): 145-9, 1992.
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Lurain JR: The significance of positive peritoneal cytology in endometrial cancer. Gynecol Oncol 46 (2): 143-4, 1992.
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Lurain JR, Rice BL, Rademaker AW, et al.: Prognostic factors associated with recurrence in clinical stage I adenocarcinoma of the endometrium. Obstet Gynecol 78 (1): 63-9, 1991.
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Ingram SS, Rosenman J, Heath R, et al.: The predictive value of progesterone receptor levels in endometrial cancer. Int J Radiat Oncol Biol Phys 17 (1): 21-7, 1989.
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Creasman WT: Prognostic significance of hormone receptors in endometrial cancer. Cancer 71 (4 Suppl): 1467-70, 1993.
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Carcangiu ML, Chambers JT, Voynick IM, et al.: Immunohistochemical evaluation of estrogen and progesterone receptor content in 183 patients with endometrial carcinoma. Part I: Clinical and histologic correlations. Am J Clin Pathol 94 (3): 247-54, 1990.
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Chambers JT, Carcangiu ML, Voynick IM, et al.: Immunohistochemical evaluation of estrogen and progesterone receptor content in 183 patients with endometrial carcinoma. Part II: Correlation between biochemical and immunohistochemical methods and survival. Am J Clin Pathol 94 (3): 255-60, 1990.
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Hetzel DJ, Wilson TO, Keeney GL, et al.: HER-2/neu expression: a major prognostic factor in endometrial cancer. Gynecol Oncol 47 (2): 179-85, 1992.
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