FIGO Stage
Although not perfect, FIGO stage is the single strongest prognostic parameter for women with endometrial carcinoma.^1-4 The 1971 FIGO clinical staging system (based upon sounding of the uterus, fractional curettage, and pelvic examination) proved to be less accurate than histologic evaluation of the hysterectomy specimen.^1,3 Determination of spread of tumor to the cervix (stage II) based on fractional curettage had an error rate of approximately 50%.^1,3 Decrease in preoperative radiotherapy practice caused FIGO in 1988 to change from a clinical to a surgical-pathologic staging system (Table 1). Endometrial carcinomas are divided into 4 stages: (I) confined to the uterine corpus; (II) extension to the uterine cervix; (III) involvement of pelvic organs (true pelvis); and (IV) spread beyond the true pelvis. The vast majority of patients have tumors limited to the uterus.

Stage I disease has 3 subdivisions based on the extent of tumor invasion into the uterine wall. Nevertheless, the best method for assessment of depth of myometrial invasion has not been established. Also, the 2 subdivisions of stage II (endocervical gland involvement and cervical stromal invasion) are hard to distinguish and the prognostic value of such distinction has been questioned.^5,6 In some series, however, the outcome of stage IIA G1 cases was significantly better than the outcome of stage IC G3 cases.⁷ Cervical involvement usually results from direct surface or stromal extension and only occasionally is secondary to implantation or lymphatic spread.⁵ Implantation occurs in the denuded endocervix following fractional curettage in about 5% of the cases.⁵ The adverse prognostic significance of stage IIIA (based on tumor involvement of the uterine serosa or positive peritoneal cytology) has not been universally confirmed.⁸ Serosal invasion represents the extreme of deep myometrial invasion of stage I disease. It is quite different from adnexal spread and the two should not be lumped.⁷ Surface involvement of the uterus is classified as stage III. Surface involvement of the ovary may well be stage I. The latter seems appropriate; the former does not.⁷ Prognosis with lymph node metastasis in the pelvis seems more favorable than lymph node metastases to the para-aortic chain, and again these two findings are lumped.⁷

Histologic grade
The prognostic value of grading endometrial adenocarcinomas has been recognized for many years.^9,10 The 1988 FIGO/ISGP grading system is based primarily upon architectural features.¹¹ Tumors that are 5% or less solid are grade 1, those that are 6% to 50% solid are grade 2, and those that are greater than 50% solid are grade 3. Areas of squamous differentiation are not considered as solid tumor growth; solid growth is based only on the glandular component. The presence of grade 3 nuclear features, however (i.e., marked nuclear pleomorphism, coarse chromatin, prominent nucleoli), in architecturally grade 1 or 2 tumors increases their grade by one.¹⁰ Most endometrioid carcinomas are architecturally grade 1 and assessment of whether the nuclear features are grade 3 is highly subjective. Nevertheless, in serous carcinoma, clear cell carcinoma, and squamous cell carcinoma, nuclear grading takes precedence.

Subsequent modifications to the FIGO grading scheme have been suggested but not formally adopted. Taylor et al.¹² have proposed a two-tiered grading system (based on the FIGO system) in which low-grade tumors have 20% or less nonsquamous solid areas, whereas high-grade tumors exhibit more than 20% nonsquamous solid areas. They found that this system had higher reproducibility and same or better prognostic significance than the three grade system. Recently, Lax et al.¹³ also proposed a binary architectural grading system based on the presence of greater than 50% solid growth (without distinction of squamous from glandular epithelium), a diffusely infiltrative growth pattern, and tumor cell necrosis. High grade tumors should exhibit at least two of the three previous criteria. This system stratified patients in three prognostic groups: a) patients with low-stage (Ia or Ib) low-grade tumors had a 100% 5-year survival rate; b) patients with higher stage (Ic and II-IV) low-grade tumors and those with high-grade tumors confined to the myometrium (Ib and Ic) had a 5-year survival rate of 67% to 76%, and patients with advanced stage high grade tumors had a 26% 5-year survival rate.¹³

Histologic type
The cell type has consistently been recognized as an important predictor of the biologic behavior of endometrial carcinoma. Over the last 15 years, and based on Bokhman's¹⁴ dualistic model for explaining the pathogenesis of endometrial carcinoma, these tumors have been classified into two types: type I tumors (about 80%) are endometrioid carcinomas frequently preceded by complex and atypical hyperplasia and associated with estrogenic stimulation. Type I tumors occur predominantly in pre or perimenopausal women and are associated with obesity, hyperlipidemia, anovulation, infertility, and late menopause. Typically, most endometrioid carcinomas are confined to the uterus and follow a favorable course. In contrast, type II tumors (about 20%) are non-endometrioid (largely serous) carcinomas, arising occasionally in endometrial polyps or from precancerous lesions that develop in atrophic endometria (endometrial "intraepithelial" carcinoma).¹⁵ Type II tumors are not associated with estrogen stimulation or hyperplasia, readily invade the myometrium and vascular spaces, and carry a high mortality rate.

It has also been found that the molecular alterations involved in the development of endometrioid (type I) carcinomas are different from those of the serous (type II) carcinomas^16-18 Whereas 25-30% of endometrioid carcinomas show microsatellite instability (MI) and less than 10% exhibit p53 mutations, the vast majority of serous carcinomas show p53 mutations, loss of heterozygosity (LOH) on several chromosomes, and only rarely microsatellite instability^16-18 (Table 2).

Although the dualistic model appears applicable to paradigmatic cases at both clinicopathological and molecular levels, there is often overlapping in the clinical, pathological, immunohistochemical, and molecular characteristics of the tumors.¹⁷ For instance, it has been shown that some nonendometrioid carcinomas (type II) may develop from preexisting endometrioid carcinomas (type I) as a result of tumor progression. Obviously, these tumors may share the pathologic and molecular features of types I and II endometrial carcinoma.^17,18

Adenocarcinoma with squamous differentiation (which occurs in about 25% of endometrial cancers) is considered a variant of endometrioid carcinoma and, as stated earlier, the grade of the glandular rather than the squamous component is a better prognostic indicator for these tumors.^19-21 Villoglandular adenocarcinomas are also considered another variant of endometrioid endocarcinoma with no significant difference in behavior.22,23 In contrast, serous and clear cell carcinomas are frequently lethal tumors with overall 5-year survival rate from 30% to 70%.^22,24-32

Myometrial invasion
In low-stage endometrial carcinomas, myometrial invasion is an independent predictor of outcome.^9,33-38 Recognizing myometrial invasion is straightforward when glands that are irregularly shaped, haphazardly distributed, and surrounded by a desmoplastic stroma, exhibit an infiltrative border with the myometrium. Occasionally, however, a carcinoma that has not invaded the myometrium shows an irregular endomyometrial junction in which rounded nests of tumor seem to protrude into the inner myometrium, and are misinterpreted as evidence of superficial myometrial invasion. On the other hand, truly myoinvasive tumors may show an expansile or pushing border. This problem is usually resolved by including blocks of tumors with adjacent normal endomyometrial junction.³⁹ Another pattern of myometrial invasion is characterized by single glands, widely scattered throughout the myometrium (adenoma malignum pattern of invasion).⁴⁰ The adverse prognostic significance of this pattern is not universally accepted.^37,40

The 1988 FIGO staging of endometrial carcinoma subdivides stage I tumors into: IA (tumor confined to the endometrium); IB (invasion limited to the inner half of the myometrium); and IC (tumor invasion to the outer half of the myometrium) (Table 1). Several other methods (including division of myometrial thickness by thirds, depth of tumor invasion in mm, or distance between the tumor and the uterine serosa in mm) have been effectively used. In a study of over 400 patients with clinical stage I endometrioid carcinomas, Zaino et al.²⁰ found that the 5-year survival was 94% when the tumor was confined to the endometrium, 91% when the tumor involved the inner third of the myometrium, 84% when the tumor extended into the middle third, and 59% when the tumor infiltrated the outer third of the myometrium. DiSaia et al.41 found that the risk of extrauterine extension for intraendometrial tumors was only 8%; tumors invading the inner third had a 12% risk, and those invading the full myometrial thickness, 46% risk.

The decision to perform pelvic and para-aortic lymph node sampling/dissection is largely based on depth of myometrial invasion (also on cell type and histologic grade). Intraoperatively, the pathologist may be requested to assess these features by frozen section.^42,43 A pilot study revealed a usable algorithm for a reasonable likelihood of finding metastatic disease: for tumors confined to the endometrium (all histologic grades) the risk was negligible; for superficial myometrial invasion, the risk was substantial only for G3 carcinomas; for middle third invasion, the risk was substantial for G2 and 3. And for deep myometrial invasion, all grades of tumor had substantial risk (20-45%) (Table 3).⁴⁴

When endometrial carcinoma and adenomyosis coexist, the latter lesion is involved by carcinoma in about 25% of the cases. According to three reports,^45-47 comprising a total of 50 patients, criteria used for distinguishing adenomyotic involvement by carcinoma from true myometrial invasion include: a) presence of endometrial stroma; b) presence of benign endometrial glands; and c) absence of inflammatory response and desmoplasia. Tumor involvement of adenomyotic foci is not associated with a worse prognosis.^45-47

Vascular invasion
The presence of tumor cells within endothelial lined spaces is a strong predictor of tumor recurrence and death from tumor, independent of myometrial invasion.^48-50 Stromal retraction is a frequent artifact which may simulate vascular invasion. Immunoperoxidase staining of endothelial cells (factor VIII or CD31) may facilitate recognition of vascular channels.³⁷ Presence of lymphatic invasion is highly suggestive of lymph node metastases.38,50 Vascular invasion occurs in 35-95% of serous carcinomas.^24-28

Peritoneal cytology
The presence of malignant cells in peritoneal washings at the time of hysterectomy justifies FIGO classification of the case as stage IIIA. Positive peritoneal cytology is often associated with other risk factors such as high grade, deep myometrial invasion, and extrauterine spread.^{8, 51, 52} Nevertheless, some investigators have found a statistically significant difference in survival for patients with clinical stage I and II disease.^37,51

Ploidy
Approximately two thirds of endometrioid carcinomas are diploid by flow or image cytometry. Diploid tumors are less aggressive, invade only superficially, and are better differentiated than aneuploid tumors.^8,52-56 Differences in disease-free survival for stage I tumors have been as significant as 94% for diploid tumors versus 64% for aneuploid carcinomas.^57-59

Steroid receptors
Most endometrioid carcinomas contain cells with both estrogen (ER) and progesterone receptors (PR) as a sign of differentiation. Currently, assessment of ER and PR is performed by immunohistochemistry. Characteristically, endometrioid carcinomas exhibit marked heterogeneity in ER and PR distribution. The presence and quantity of steroid receptors correlate with FIGO stage, histologic grade, and survival.^60-63 Nevertheless, because of great variation in reported data, ER and PR are not routinely measured in hysterectomy specimens. In contrast, measurement of steroid receptors in metastases may be helpful for establishing appropriate treatment.

Markers of proliferation
Mitotic count, S-phase fraction by flow cytometry, and proportion of proliferating cells by immunohistochemistry (PCNA, Ki-67, MIB-1) are the methods most commonly used. Ki-67 and MIB-1 identify cells in most of G1, S, G2, and M phases of the cell cycle.64-66 Presently, data in the literature are insufficient to establish the prognostic validity of these methods.

References

1. Abeler VM, Kjorstad KE. Endometrial adenocarcinoma in Norway. A study of a total population. Cancer 1991; 67: 3093-4003.
2. Gal D, Recio FO, Zamurovic D. The new International Federation of Gynecology and Obstetrics surgical staging and survival rates in early endometrial carcinoma. Cancer 1992; 69:200-202.
3. Wolfson A, Slightler S, Markoe A et al. The prognostic significance of surgical staging for carcinoma of the endometrium. Gynecologic Oncology 1992; 45: 142-146.
4. Kosary CL. FIGO stage, histology, histologic grade, age and race as prognostic factors in determining survival for cancers of the female gynecological system: an analysis of 1973-87 SEER cases of cancer of the endometrium, cervix, ovary, vulva, and vagina. Sem Surg Oncol 1994; 10: 31-46.
5. Fanning J, Alvarez P, Tsukada Y, Piver MS. Prognostic significance of the extent of cervical involvement by endometrial cancer. Gynecol Oncol 1991; 40: 46-47.
6. Eltabbakh G, Moore A. Survival of women with surgical stage II endometrial cancer. Gynecol Oncol 1999; 74: 80-85.
7. Boronow RC. Surgical staging of endometrial cancer: Eolution, evaluation, and responsible challenge –A personal perspective. Gynecol Oncol 1997; 66:179-189.
8. Kadar N, Homesley HP, Malfetano JH. Positive peritoneal cytology is an adverse risk factor in endometrial carcinoma only if there is other evidence of extrauterine disease. Gynecol Oncol 1992; 46: 145-149.
9. Abeler VM, Kjordstad KE, Berle E. Carcinoma of the endometrium in Norway: a histopathological and prognostic survey of a total population. Int J Gynecol Cancer 1992; 2: 9-22
10. Zaino RJ, Kurman RJ, Diana KL, Morrow CP. The utility of the revised International Federation of Gynecology and Obstetrics histologic grading of endometrial adenocarcinoma using a defined nuclear grading system. A Gynecologic Oncology Group study. Cancer 1995; 75: 81-86.
11. Announcements. FIGO stages - 1998 revision. Gynecol Oncol 1989; 35: 125-127.
12. Taylor RR, Zeller J, Lieberman RW, et al. An analysis of two versus three grades for endometrial carcinoma. Gynecol Oncol 1999; 74: 3-6.
13. Lax SF, Kurman RJ, Pizer ES, et al. A binary architectural grading system for uterine endometrial endometrioid carcinoma has superior reproducibility compared with FIGO grading and identifies subsets of advanced-stage tumors with favorable and unfavorable prognosis. Am J Surg Pathol 2000; 24: 1201-1208.
14. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 1983; 15:10-17.
15. Ambros RA, Sherman ME, Zahn ChM, et al. Endometrial intraepithelial carcinoma: A distinctive lesion specifically associated with tumors displaying serous differentiation. Hum Pathol 1995; 26:1260-1267
16. Lax SF, Kurman RJ. A dualistic model for endometrial carcinogenesis based on immunohistochemical and molecular genetic analysis. Verh Dtsch Ges Path 1997; 81:228-232.
17. Catasús Ll, Machín P, Matias-Guiu X, Prat J. Microsatellite instability in endometrial carcinomas. Clinicopathologic correlations in a series of 42 cases. Hum Pathol 1998; 29:1160-1164.
18. Matias-Guiu X, Catasús Ll, Bussaglia E, et al. Molecular pathology of endometrial hyperplasia and carcinoma. Hum Pathol 2001; 32:569-577.
19. Hendrickson MR, Kempson RL. Surgical pathology of the uterine corpus. Major problems in pathology. WB Saunders, Philadelphia 1980.
20. Zaino RJ, Kurman RJ, Herbold D, et al. The significance of squamous differentiation in endometrial carcinoma. Cancer 1991; 68:2293-2302.
21. Abeler VM, Kjorstad KE. Endometrial adenocarcinoma with squamous differentiation. Cancer 1992; 69:488-495.
22. Chen JL, Trost DC, Wilkinson EJ. Endometrial papillary adenocarcinomas: two clinicopathologic types. Int J Gynecol Pathol 1985; 4:279-288.
23. Ward BG, Wright RG, Free K. Papillary carcinomas of the endometrium. Gynecol Oncol 1990; 39:347-351.
24. Hendrickson MR, Ross J, Eifel P, et al. Uterine papillary serous carcinoma: a highly malignant form of endometrial adenocarcinoma. Am J Surg Pathol 1982; 6:93-108.
25. Chambers JT, Merino M, Kohorn EI, et al. Uterine papillary serous carcinoma: Obtet Gynecol 1987; 69:109-113.
26. Abeler VM, Kjorstad KE. Serous papillary carcinoma of the endometrium: a histopathological study of 22 cases. Gynecol Oncol 1990; 39: 266-271.
27. Carcangiu ML. Chambers JT. Uterine papillary serous carcinoma: a study of 108 cases with emphasis on the prognostic significance of associated endometrioid carcinoma, absence of invasion, and concomitant ovarian carcinoma. Gynecol Oncol 1992; 47:298-305.
28. Prat J, Oliva E, Lerma E, et al. Uterine papillary serous adenocarcinoma: A 10-case study of p53 and c-erbB-2 expression and DNA content. Cancer 1994; 74:1778-1783.
29. Abeler VM, Kjorstad KE. Clear cell carcinoma of the endometrium: a histopathologic and clinical study of 97 cases. Gynecol Oncol 1991; 40: 207-217.
30. Carcangiu ML. Chambers JT. Early pathologic stage clear cell carcinoma and uterine papillary serous carcinoma of the endometrium: comparison of clinicopathologic features and survival. Int J Gynecol Pathol 1995; 14:30-38.
31. Abeler VM, Vergote IB, Kjorstad KE, Trope CG. Clear cell carcinoma of the endometrium. Cancer 1996; 78:1740-1747.
32. Aquino-Parsons C, Lim P, Wong F, Mildenberger M. Papillary serous and clear cell carcinoma limited to endometrial curettings in FIGO stage 1a and 1b endometrial adenocarcinoma: treatment implications. Gynecol Oncol 1998; 71: 83-86.
33. Eifel P, Ross J, Hendrickson M, et al. Adenocarcinoma of the endometrium: analysis of 262 cases with disease limited to the uterine corpus: treatment comparisons. Cancer 1983; 52:1026-1031.
34. Creasman WT, Morrow CP, Bundy BN, et al. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer 1987; 60:2035-2041.
35. 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 1991; 40:55-65.
36. Ambros RA, Kurman RJ. Identification of patients with stage I uterine endometrioid adenocarcinoma at high risk of recurrence by DNA ploidy, myometrial invasion, and vascular invasion. Gynecol Oncol 1992; 45:235-239.
37. Lee KR, Vacek PM, Belinson JL. Traditional and nontraditional histopathologic predictors of recurrence in uterine endometrioid adenocarcinoma. Gynecol Oncol 1994; 54:10-18.
38. Zaino RJ, Kurman RJ, Diana KL, Morrow CP. Pathologic models to predict outcome for women with endometrial adenocarcinoma: the importance of the distinction between surgical stage and clinical stage – a Gynecologic Oncology Group study. Cancer 1996; 77:1115-1121.
39. Clement PB, Young RH. Endometrioid carcinoma of the uterine corpus: A review of its pathology with emphasis on recent advances and problematic aspects. Adv Anat Pathol 2002; 9:145-184
40. Longacre TA, Hendrickson MR. Diffusely infiltrative endometrial adenocarcinoma. An adenoma malignum pattern of myoinvasion. Am J Surg Pathol 1999; 23:69-78.
41. DiSaia PJ, Creasman WT, Boronow RC et al. Risk factors and recurrent patterns in stage I endometrial cancer. Am J Obstet Gynecol 1985; 151:1009-1015.
42. Fanning J, Tsukada Y, Piver MS. Intraoperative frozen section diagnosis of depth of myometrial invasion in endometrial adenocarcinoma. Gynecol Oncol 1990; 37:47-50.
43. Goff BA, Rice LW. Assessment of depth of myometrial invasion in endometrial adenocarcinoma. Gynecol Oncol 1990; 38:46-48.
44. Boronow RC, Morrow CP, Creasman WT, et al. Surgical staging in endometrial cancer: clinical-pathologic findings of a prospective study. Obstet Gynecol 1984; 63:825-832.
45. Hall B, Young RH, Nelson JH. The prognostic significance of adenomyosis in endometrial carcinoma. Gynecol Oncol 1984; 17:32-40.
46. Jacques SM, Lawrence WD. Endometrial adenocarcinoma with variable-level myometrial involvement limited to adenomyosis: a clinicopathologic study of 23 cases. Gynecol Oncol 1990; 37:401-407.
47. Mittal KR, Barwick KW. Endometrial adenocarcinoma involving adenomyosis without true myometrial invasion is characterized by frequent preceding estrogen therapy, low histologic grades, and excellent prognosis. Gynecol Oncol 1993; 49:197-201.
48. Hanson MB, van Nagell JR, Powell DE. The prognostic significance of lymph-vascular space invasion in Stage I endometrial cancer. Cancer 1985; 55:1753-1757.
49. Sivridis E, Buckley CH, Fox H. The prognostic significance of lymphatic vascular space invasion in endometrial adenocarcinoma. Br J Obstet Gynaecol 1987; 94:991-994.
50. Gal D, Recio FO, Zamurovic D, Tancer ML. Lymphvascular space involvement –a prognostic indicator in endometrial adenocarcinoma. Gynecol Oncol 1991; 42:142-145.
51. Turner DA, Gershenson DM, Atkinson N, et al. The prognostic significance of peritoneal cytology for stage I endometrial cancer. Obstet Gynecol 1989; 74:775-780.
52. Grimshaw R, Tupper W, Fraser R, et al. Prognostic value of peritoneal cytology in endometrial carcinoma. Gynecol Oncol 1990; 36:97-100.
53. Geisinger KK, Homesley HD, Morgan TM, et al. Endometrial adenocarcinoma. A multiparameter clinicopathologic analysis including the DNA profile and the sex steroid hormone receptors. Cancer 1986; 58:1518-1525.
54. Van Der Putten H, Baak JPA, Koenders T, et al. Prognostic value of quantitative pathologic features and DNA content in individual patients with stage I endometrial adenocarcinoma. Cancer 1989; 63:1378-1387.
55. Sorbe B, Risberg B, Frankendal B. DNA ploidy, morphometry, and nuclear grade as prognostic factors in endometrial carcinoma. Gynecol Oncol 1990; 38:22-27.
56. Stendahl U, Strang P, Wagenius G, et al. Prognostic significance of proliferation in endometrial adenocarcinomas: a multivariate analysis of clinical and flow cytometric variables. Int J Gynecol Pathol 1991; 10:271-284.
57. Britton L, Wilson T, Gaffey T, et al. Flow cytometric DNA analysis of stage I endometrioid carcinoma. Gynecol Oncol 1989; 34:317-322.
58. Pisani AL, Barbuto DA, Chen D, et al. HER-2/neu, p53, and DNA analyses as prognosticators for survival in endometrial carcinoma. Obstet Gynecol 1995; 85:729-734.
59. Nordstrom B, Strang P, Lindgren A, et al. Carcinoma of the endometrium: do the nuclear grade and DNA ploidy provide more prognostic information than do the FIGO and WHO classifications? Int J Gynecol Pathol 1996; 15:191-201.
60. Deligdisch L, Holinka C. Progesterone receptors in two groups of endometrial carcinoma. Cancer 1986; 571385-1388.
61. Geisinger KK, Marshall RB, Kute TE, Homesley HD. Correlation of female sex steroid hormone receptors with histologic and ultrastructural differentiation in adenocarcinoma of the endometrium. Cancer 1986; 58:1506-1517.
62. Carcangiu ML, Chambers JT, Voynick I, 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 1990; 94:255-260.
63. Kadar N, Malfetano JH, Homesley HD. Steroid receptor concentrations in endometrial carcinoma: effect on survival in surgically staged patients. Gynecol Oncol 1993; 50:281-286.
64. Lax SF, Piezer ES, Ronnett BM, Kurman RJ. Clear cell carcinoma of the endometrium is characterized by a distinctive profile of p53, Ki-67, estrogen, and progesterone receptor expression. Hum Pathol 1998; 29:551-558.
65. Salvesen HB, Iversen OE, Akslen LA. Identification of high-risk patients by assessment of nuclear Ki-67 expression in a prospective study of endometrial carcinomas. Clin Cancer Res 1998; 4:2779-2785.
66. Pfisterer J, Kommoss F, Sauerbrei W, et al. Prognostic value of DNA ploidy and S-phase fraction in stage I endometrial carcinoma. Gynecol Oncol 1995; 58:149-156.

Table 1 - Staging of endometrial adenocarcinoma, FIGO 1988 (1989)

Stage I: Carcinoma is confined to the corpus uteri itself   Stage Ia: Tumor limited to the endometrium   Stage Ib: Invasion to < 1/2 of the myometrium   Stage Ic: Invasion to > 1/2 of the myometrium Stage II: Carcinoma has involved the corpus and the cervix   Stage IIa: Endocervical glandular involvement only   Stage IIb: Cervical stromal invasion Stage III: Carcinoma has extended outside the uterus but not outside the true pelvis   Stage IIIa: Tumor invades serosa and/or adnexae and/or positive peritoneal cytology   Stage IIIb: Vaginal metastases   Stage IIIc: Metastases to pelvic and/or para-aortic lymph nodes Stage IV: Carcinoma has extended outside the true pelvis or has obviously involved the mucosa of the bladder or the rectum   Stage IVa: Tumor invasion of bladder and/or bowel mucosa   Stage IVb: Distant metastases including intraabdominal and/or inguinal lymph nodes

TABLE 2 - The two types of Endometrial Carcinoma

	Type I	Type II
Age	Pre- and Perimenopausal	Postmenopausal
Unopposed Estrogen	Present	Absent
Hyperplasia-Precursor	Present	Absent
Grade	Low	High
Myometrial Invasion	Minimal	Deep
Specific Subtypes	Endometrioid	Serous
		Clear cell
Behavior	Stable	Progressive
Genetic alterations	Microsatellite instability	P53 mutations, LOH
(Modified from Bokhman, 1983).

TABLE 3 - Risk Features for Lymph Node Metastasis

	Negligible risk
Myometrial invasion	None, G1, G2, G3 Inner one-third, G1, G2 Middle one-third, G1
Vascular invasion Occult spread to cervix and/or adnexae Cell type	None None Endometrioid
	Substantial risk
Myometrial invasion	Inner one-third, G3 Middle one-third, G2, G3 Outer one-third, G1, G2, G3
Vascular invasion Occult spread to cervix and/or adnexae Cell type	Present Present Endometrioid G3; serous; clear cell
Modified from Boronow (1987), and Boronow et al. (1984)

Endometrial Carcinoma - (Adverse Risk Factors)

Nonendometrioid histology Grade 2-3 Myometrial invasion Cervical invasion Suspicious lymph nodes Morrow CP, 1996