Note: Separate PDQ summaries on Uterine Sarcoma Treatment, Screening for Endometrial Cancer and Prevention of Endometrial Cancer are also available.

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, although a retrospective study found a strong correlation between positive cervical cytology and high-risk disease (i.e., high-grade tumor and deep myometrial invasion) [1] as well as an increased risk of nodal disease.[2] 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.[3,4] In contrast, combined estrogen and progesterone therapy prevents the increase in risk of endometrial cancer associated with unopposed estrogen use.[5,6] 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, perhaps related to the estrogenic effect of tamoxifen on the endometrium.[7,8] 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.[9,10] 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.[11] 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.[12] Patients with grade 2 or 3 tumors and invasion of less than one half 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 4 statistically significant adverse prognostic factors: myometrial invasion, vascular invasion, 8 or more mitoses per ten high-power fields, and an absence of progesterone receptors.[13]

Another group identified aneuploidy and a high S-phase fraction as predictive of poor prognosis.[14] A Gynecologic Oncology Group (GOG) 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). Ninety-eight percent of the cases with aortic node metastases were in patients with positive pelvic nodes, intra-abdominal metastases, or tumor invasion of the outer one third of the myometrium.[15,16]

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.[17-22] 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 greater than 100 had a 3-year disease-free survival of 93% compared with 36% for a level less than 100. Only cervical involvement and peritoneal cytology were significant prognostic variables after adjusting for progesterone receptor levels.[23] Other reports confirm the importance of hormone receptor status as an independent prognostic factor.[24] 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 (FIGO) grade as well as survival.[25-27] 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.[27] For example, overexpression of the HER-2/neu oncogene has been associated with a poor overall prognosis.[28] A general review of prognostic factors has been published.[29]

References

1. DuBeshter B, Warshal DP, Angel C, et al.: Endometrial carcinoma: the relevance of cervical cytology. Obstet Gynecol 77 (3): 458-62, 1991.  [PUBMED Abstract]
   
   
2. 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.  [PUBMED Abstract]
   
   
3. Ziel HK, Finkle WD: Increased risk of endometrial carcinoma among users of conjugated estrogens. N Engl J Med 293 (23): 1167-70, 1975.  [PUBMED Abstract]
   
   
4. Jick SS, Walker AM, Jick H: Estrogens, progesterone, and endometrial cancer. Epidemiology 4 (1): 20-4, 1993.  [PUBMED Abstract]
   
   
5. Jick SS: Combined estrogen and progesterone use and endometrial cancer. Epidemiology 4 (4): 384, 1993.  [PUBMED Abstract]
   
   
6. Bilezikian JP: Major issues regarding estrogen replacement therapy in postmenopausal women. J Womens Health 3(4): 273-282, 1994. 
   
   
7. 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.  [PUBMED Abstract]
   
   
8. 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.  [PUBMED Abstract]
   
   
9. 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.  [PUBMED Abstract]
   
   
10. 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.  [PUBMED Abstract]
    
    
11. 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.  [PUBMED Abstract]
    
    
12. 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.  [PUBMED Abstract]
    
    
13. Tornos C, Silva EG, el-Naggar A, et al.: Aggressive stage I grade 1 endometrial carcinoma. Cancer 70 (4): 790-8, 1992.  [PUBMED Abstract]
    
    
14. 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.  [PUBMED Abstract]
    
    
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 40 (1): 55-65, 1991.  [PUBMED Abstract]
    
    
16. 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.  [PUBMED Abstract]
    
    
17. 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.  [PUBMED Abstract]
    
    
18. 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.  [PUBMED Abstract]
    
    
19. 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.  [PUBMED Abstract]
    
    
20. 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.  [PUBMED Abstract]
    
    
21. Lurain JR: The significance of positive peritoneal cytology in endometrial cancer. Gynecol Oncol 46 (2): 143-4, 1992.  [PUBMED Abstract]
    
    
22. 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.  [PUBMED Abstract]
    
    
23. 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.  [PUBMED Abstract]
    
    
24. Creasman WT: Prognostic significance of hormone receptors in endometrial cancer. Cancer 71 (4 Suppl): 1467-70, 1993.  [PUBMED Abstract]
    
    
25. 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.  [PUBMED Abstract]
    
    
26. 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.  [PUBMED Abstract]
    
    
27. Gurpide E: Endometrial cancer: biochemical and clinical correlates. J Natl Cancer Inst 83 (6): 405-16, 1991.  [PUBMED Abstract]
    
    
28. 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.  [PUBMED Abstract]
    
    
29. Homesley HD, Zaino R: Endometrial cancer: prognostic factors. Semin Oncol 21 (1): 71-8, 1994.  [PUBMED Abstract]
    
    

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