Preoperative markers for the prediction of high-risk features in endometrial cancer

Table 1 Baseline clinicopathological characteristics, n (%)

Characteristics	n = 128
Age (yr), mean ± SD	57.4 ± 10.9
BMI (kg/m2), mean ± SD	27.7 ± 7.5
Obesity (BMI > 30 kg/m2)	37 (28.9)
Parity
Nulliparous	61 (47.7)
Multiparous	67 (52.3)
Menopausal status
Premenopause	39 (30.5)
Postmenopause	89 (69.5)
Coexisting medical diseases1	80 (62.5)
Pre-existing breast cancer	12 (9.4)
Coexisting benign gynecologic diseases2	72 (56.3)
Surgical stage of disease
Stage I	86 (67.2)
Stage II	15 (11.7)
Stage III	19 (14.8)
Stage IV	8 (6.3)
Histologic grade
Grade 1 endometrioid carcinoma	71 (55.5)
Grade 2 endometrioid carcinoma	23 (18.0)
Grade 3 endometrioid carcinoma	31 (24.2)
Uterine papillary serous carcinoma	2 (1.6)
Carcinosarcoma	1 (0.8)

¹Medical diseases included hypertension, dyslipidemia, heart disease, thyroid disease, and connective tissue diseases;

²Benign gynecologic diseases such as leiomyoma, adenomyosis, or pelvic and ovarian endometriosis. BMI: Body mass index.

Table 2 Comparison of clinical characteristics between endometrial cancer patients with and without high-risk features¹, n (%)

Characteristics	Patients with high-risk features (n = 74)	Patients without high-risk features (n = 54)	P value
Age (yr), mean ± SD	60.1 ± 10.7	53.7 ± 10.2	0.001
BMI (kg/m2), mean ± SD	27.1 ± 7.8	28.5 ± 7.1	0.32
Obese (BMI > 30 kg/m2)	16 (21.6)	21 (38.9)	0.05
Nulliparous	41 (47.7)	26 (48.1)	0.48
Postmenopause	59 (79.7)	30 (55.6)	0.006
Coexisting medical diseases	46 (62.2)	34 (63.0)	1.00
Coexisting benign gynecologic diseases	42 (56.8)	30 (55.56)	1.00
CA125 level, median (min-max)	27.0 (7.1-786.8)	16.3 (5.3-432.1)	0.002
HE4 level, median (min-max)	130.6 (39.4-1719.0)	81.7 (30.5-293.9)	0.005

¹High risk features included grade 3 tumors, large tumor sizes, deep myometrial invasion, lymphovascular space invasion, cervical metastasis, extrauterine metastasis and nodal metastasis. BMI: Body mass index; CA125: Cancer antigen 125; HE4: Human epididymis protein 4.

Table 3 Associations between cancer antigen 125 and human epididymis protein 4 and various pathological characteristics

Pathological characteristics		No. of cases	CA125 (U/mL)		HE4 (pmol/L)
			Median	Min-Max	Median	Min-Max
Tumor size	≤ 2 cm	38	16.1	6.9-556.4	68.9	30.5-649.1
	> 2 cm	90	23.8	5.3-786.8	128.3	35.0-1719.0
			P = 0.03		P < 0.001
Tumor grade	1 + 2	93	22.1	5.3-786.8	98.8	30.5-1132.0
	3	35	20.6	7.1-556.4	117.7	43.6-1719.0
			P = 0.71		P = 0.78
Myometrial invasion	≤ 50%	69	19.1	5.3-786.8	83.0	30.5-860.2
	> 50%	59	27.5	7.1-479.5	130.6	39.4-1719.0
			P = 0.01		P = 0.006
Lymphovascular space invasion	No	95	19.4	5.3-786.8	88.3	30.5-1132.0
	Yes	33	55.8	11.7-479.5	165.7	39.4-1719.0
			P < 0.001		P = 0.003
Cervical involvement	No	102	21.3	5.3-786.8	94.3	30.5-860.2
	Yes	26	25.0	10.0-479.5	300.0	39.4-1719.0
			P = 0.15		P = 0.05
Extrauterine metastasis	No	91	19.1	5.3-556.4	87.0	30.5-585.3
	Yes	37	54.6	10.0-786.8	183.5	39.4-1719.0
			P < 0.001		P < 0.001
Node metastasis	Negative	106	19.3	5.3-786.8	93.0	30.5-1132.0
	Positive	13	57.0	11.7-439.2	128.6	39.4-1719.0
			P = 0.004		P = 0.15
Any high-risk features	No	55	16.3	5.3-432.1	81.7	30.5-293.9
	Yes	73	27.5	7.1-786.8	130.5	39.4-1719.0
			P < 0.001		P < 0.001
Stage of disease	Early	101	19.3	5.3-786.8	89.5	30.5-1132.0
	Advanced	27	57.0	9.5-479.5	283.0	39.40 - 1719.0
			P < 0.001		P < 0.001

CA125: Cancer antigen 125; HE4: Human epididymis protein 4.

Table 4 Cut-off values of cancer antigen 125 and HE4 to predict high-risk features in clinical stage 1 postmenopausal endometrial cancer patients

	Cut-off value	AUC	P value	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)
CA125	20 U/mL	0.72	0.002	64.0	72.3	69.8	66.8
HE4	113 pmol/L	0.70	0.006	64.0	77.3	73.8	68.2

AUC: Area under the concentration-time curve; PPV: Positive predictive value; NPV: Negative predictive value; CA125: Cancer antigen 125; HE4: Human epididymis protein 4.