CA125, CEA, CA19-9, and Heteroploid Cells in Ascites Fluid May Help Diagnose Peritoneal Carcinomatosis in Patients with Gastrointestinal and Ovarian Malignancies

Figures & data

Table 1 Patient Characteristics

Characteristics	CRC (N=32)	GC (N=38)	OC (N=32)
Age (years)
Median	57	59	55
Range	29–79	39–80	37–75
Gender, n(%)
Male	19(59.4)	24(63.2)	0(0)
Female	13(40.6)	14(36.8)	32(100.0)
Performance status
(ECOG), n(%)
1	7(21.8)	13(34.2)	12(37.5)
2	15(46.9)	21(55.3)	16(50.0)
3	10(31.3)	4(10.5)	4(12.5)
Tumor histology, n(%)
Adenocarcinoma	32(100.0)	38(100.0)	－
Serous	－	－	22(81.3)
Mucinous	－	－	10(18.7)
Tumor site, n(%)
Right	17(53.1)	－	－
Left	15(46.9)	－	－
Tumor stage (TNM), n(%)
III	11(34.4)	12(31.6)	16(50.0)
IV	21(65.6)	26(68.4)	16(50.0)
Histologic differentiation
Well	5(15.6)	4(10.6)	4(12.5)
Moderate	17(53.1)	17(44.7)	18(56.3)
Poor	10(31.3)	17(44.7)	10(31.2)
Peritoneal metastasis, n(%)
Positive	18(56.3)	22(57.9)	18(56.3)
Negative	14(43.7)	16(42.1)	14(43.7)
Liver metastasis, n(%)
Positive	16(50.0)	17(44.7)	7(21.9)
Negative	16(50.0)	21(55.3)	25(78.1)
Ascites volume, n(%)
1500–3000mL	13(40.6)	19(50.0)	14(43.8)
over 3000 mL	19(59.4)	19(50.0)	18(56.2)
Diagnosis method of PC(N=58), n(%)
Pathological diagnosis	5(27.8)	8(36.4)	7(38.9)
CT and tumor cell in ascites	9(50.0)	14(63.6)	6(33.3)
MRI and tumor cell in ascites	4(22.2)	0(0)	5(27.8)
Gilly PC (N=58), n(%)
1	6(33.3)	4(18.2)	2(11.1)
2	4(22.2)	4(18.2)	4(22.2)
3	7(38.9)	10(45.4)	7(38.9)
4	1(5.6)	4(18.2)	5(27.8)
Treatment received
Prior chemotherapy, n(%)
Yes	16(50.0)	24(63.2)	11(34.4)
No	16(50.0)	14(36.8)	21(65.6)
Prior surgery, n(%)
Yes	15(46.9)	26(68.4)	12(37.5)
No	17(53.1)	12(31.6)	20(62.5)

Abbreviations: CRC, colorectal cancer; GC, gastric cancer; OC, ovarian cancer.

Table 2 The Ascites and Serum Tumor Marker Levels in Gastrointestinal and Ovarian Cancer Patients

Characteristics (N=102)	Ascites CEA	P-value	Serum CEA	P-value	Ascites CA19-9	P-value	Serum CA19-9	P-value	Ascites CA125	P-value	Serum CA125	P-value
Peritoneal metastasis
Positive	137.90(0.24–1000.00)	0.15^a	20.40(0.25–1000.00)	0.88^a	180.91(0.60–10,000.00)	0.06^a	53.91(0.60–10,000.00)	0.82^a	638.73 (72.98–5000.00)	<0.001^a	258.92(28.45–5000.00)	0.22^a
Negative	79.72(0.20–497.54)		17.70(0.50–290.80)		55.25(0.60–917.50)		32.34(0.60–1396.00)		372.01(35.89–1850.00)		161.82(48.02–855.62)
Tumor stage(TNM)
III	17.98 (0.20–871.56)	0.13^a	10.29 (0.25–290.80)	0.48^a	31.25 (0.60–917.50)	0.06^a	27.03(0.60–1396.00)	0.35^a	490.79 (35.89–5000.00)	0.20^a	158.90 (48.02–2501.00)	1.00^a
IV	127.58 (0.24–1000.00)		25.78 (0.28–1000.00)		202.21 (0.60–10,000.00)		68.07(0.60–10,000.00)		589.00 (72.98–5000.00)		233.20 (28.45–5000.00)
Histologic differentiation
Well	80.89 (0.35–871.56)	0.57^b	23.47(0.25–290.80)	0.97^b	50.66 (0.60–917.50)	0.54^b	43.79 (0.60–1396.00)	0.96^b	440.50 (69.85–3547.50)	0.78^b	143.60 (89.20–579.86)	0.52^b
Moderate	91.00 (0.20–1000.00)		17.70(0.28–877.20)		119.31 (0.60–10,000.00)		32.34 (0.60–9903.00)		519.54 (35.89–5000.00)		189.37 (28.45–1007.00)
Poor	127.58 (0.33–1000.00)		15.02(0.33–1000.00)		161.48 (2.12–10,000.00)		41.25 (1.64–10,000.00)		593.50 (74.58–5000.00)		270.56 (32.56–5000.00)
Liver metastasis
Positive	135.51 (0.33–1000.00)	0.07^a	32.44 (0.28–1000.00)	0.21^a	202.86 (1.20–10,000.00)	0.05^a	64.86 (1.29–9903.00)	0.38^a	591.25 (89.66–5000.00)	0.27^a	195.03 (28.45–5000.00)	0.18^a
Negative	19.93 (0.20–1000.00)		12.13 (0.25–290.80)		31.68 (0.60–10,000.00)		30.18 (0.60–10,000.00)		484.85 (35.89–5000.00)		250.73 (48.02–2501.00)
Ascites volume
1500–3000mL	84.21 (0.20–1000.00)	0.76^a	11.30 (0.50–877.20)	0.56^a	138.73 (0.60–6213.00)	0.45^a	41.27 (0.60–5371.00)	0.64^a	445.87 (69.85–5000.00)	0.04^a	158.90 (28.45–1622.00)	0.13^a
Over 3000mL	104.20 (0.24–1000.00)		23.69 (0.25–1000.00)		116.11 (1.00–10,000.00)		32.71 (0.60–10,000.00)		597.38 (35.89–5000.00)		267.08 (32.56–5000.00)

Notes: ^aMann–Whitney U-test; ^bKruskal–Wallis H-test. P<0.05.

Table 3 The Ascites and Serum Tumor Marker Levels in Gastrointestinal Cancer Patients

Characteristics (N=70)	Ascites CEA	P-value	Serum CEA	P-value	Ascites CA19-9	P-value	Serum CA19-9	P-value	Ascites CA125	P-value	Serum CA125	P-value
Peritoneal metastasis
Positive	278.50(0.63–1000.00)	0.001^a	45.76(0.77–1000.00)	0.19^a	310.86(0.60–10,000.00)	0.002^a	142.40(0.60–10,000.00)	0.08^a	563.95(72.98–2954.00)	0.001^a	190.05 (28.45–847.10)	0.22^a
Negative	118.50 (0.20–497.54)		29.90(0.94–290.80)		155.91(0.60–917.50)		74.50(0.60–1396.00)		272.85(35.89–843.20)		131.78 (48.02–584.20)
Tumor stage(TNM)
III	145.69 (0.20–871.56)	0.17^a	37.15 (1.36–290.80)	0.66^a	150.33 (0.60–917.50)	0.13^a	49.47 (0.60–1396.00)	0.36^a	314.89 (35.89–698.20)	0.06^a	135.00 (48.02–584.20)	0.48^a
IV	223.63 (0.63–1000.00)		41.13 (0.77–1000.00)		289.15 (0.60–10,000.00)		134.12 (0.60–10,000.00)		515.52 (72.98–2954.00)		189.54 (28.45–847.10)
Histologic differentiation
Well	90.54 (0.35–871.56)	0.32^b	48.78 (1.43–290.80)	0.59^b	159.60 (0.60–917.50)	0.39^b	108.90 (0.60–1396.00)	1.00^b	402.65 (69.85–1217.00)	0.47^b	135.00 (89.20–391.40)	0.38^b
Moderate	172.26 (0.20–1000.00)		39.83 (0.77–877.20)		227.92 (0.60–10,000.00)		122.64 (0.60–9903.00)		449.41 (35.89–1841.00)		140.32 (28.45–584.20)
Poor	221.23 (0.63–1000.00)		34.98 (0.94–1000.00)		297.89 (2.12–10,000.00)		127.46 (1.64–10,000.00)		497.47 (74.58–2954.00)		199.50 (41.95–847.10)
Liver metastasis
Positive	221.23 (0.63–1000.00)	0.62^a	48.88 (0.77–1000.00)	0.72^a	289.15 (2.12–10,000.00)	0.24^a	134.12 (1.64–9903.00)	0.72^a	341.36 (35.89–2954.00)	0.05^a	165.90 (28.45–382.10)	0.61^a
Negative	169.32 (0.20–1000.00)		37.15 (1.36–290.80)		202.21 (0.60–10,000.00)		119.64 (0.60–10,000.00)		541.98 (89.66–1841.00)		154.24 (48.02–847.10)
Ascites volume
1500–3000mL	144.05 (0.20–1000.00)	0.20^a	29.90 (0.77–877.20)	0.11^a	288.03 (0.60–6213.00)	0.42^a	122.64 (0.60–5371.00)	0.93^a	388.94 (69.85–1764.00)	0.16^a	133.35 (28.45–501.32)	0.07^a
Over 3000mL	227.42 (0.63–1000.00)		48.78 (0.94–1000.00)		214.43 (1.34–10,000.00)		118.18 (1.64–10,000.00)		504.01 (35.89–2954.00)		200.38 (44.48–847.10)

Notes: ^aMann–Whitney U-test; ^bKruskal–Wallis H-test. P<0.05.

Table 4 Association of Ascites Tumor Marker Levels with Gilly PC Stage in Gastrointestinal and Ovarian Cancer Patients

Category	Gilly PC Stage		P-value^a
	Stage 0–2	Stage 3–4
In gastrointestinal and ovarian cancer patients (N=58)
CA125	556.78(87.65–5000.00)	850.65(72.98–5000.00)	0.08
In gastrointestinal cancer patients (N=40)
CEA	278.50(0.63–1000.00)	231.40(0.71–1000.00)	0.74
CA19-9	289.15(2.12–10,000.00)	378.35(0.60–10,000.00)	0.70

Notes: ^aMann–Whitney U-test. P<0.05.

Table 5 Comparison of Positive Rates of Heteroploid Cells in the Two Groups

Category	Peritoneal Metastasis		x^2	P-value^a
	Positive (n, %)	Negative (n, %)
In gastrointestinal and ovarian cancer patients (N=102)
Positive	43(42.2)	14(13.7)	18.18	<0.001
Negative	15(14.7)	30(29.4)
In gastrointestinal cancer patients (N=70)
Positive	31(44.3)	7(10.0)	20.27	<0.001
Negative	9(12.9)	23(32.8)

Notes: ^aChi-square test. P<0.05.

Table 6 The Area of ROC of Ascites Tumor Markers and Heteroploid Cells in Gastrointestinal and Ovarian Cancer Patients

Category	Area	P	95% CI
CA125	0.732	<0.001	0.637–0.828
Heteroploid cells	0.703	<0.001	0.598–0.807
CA125+Heteroploid cells	0.815	<0.001	0.730–0.899

Table 7 Tumor Markers and Heteroploid Cells in the Diagnosis of PC in Gastrointestinal and Ovarian Cancer Patients

Category	Sensitivity (%)	Specificity (%)	Youden’s Index (%)
CA125	63.8	72.7	36.5
Heteroploid cells	74.1	68.2	42.3
CA125+Heteroploid cells	75.9	79.5	55.4

Figure 1 ROC of tumor markers and heteroploid cells in the diagnosis of PC in gastrointestinal and ovarian cancer patients.

Table 8 The Area of ROC of Ascites Tumor Markers and Heteroploid Cells in Gastrointestinal Cancer Patients

Category	Area	P	95% CI
CA125	0.742	0.001	0.626–0.857
CEA	0.723	0.001	0.604–0.843
CA19-9	0.718	0.002	0.597–0.839
Heteroploid cells	0.760	<0.001	0.643–0.878
CA125+Heteroploid cells	0.873	<0.001	0.787–0.960
CA125+CEA	0.813	<0.001	0.713–0.912
CA125+CA19-9	0.792	<0.001	0.686–0.897
CEA+Heteroploid cells	0.813	<0.001	0.711–0.915
CEA+CA19-9	0.788	<0.001	0.681–0.896
CA19-9+Heteroploid cells	0.819	<0.001	0.717–0.921

Table 9 Tumor Markers and Heteroploid Cells in the Diagnosis of PC in Gastrointestinal Cancer Patients

Category	Sensitivity (%)	Specificity (%)	Youden’s Index (%)
CA125	55.0	86.6	41.7
CEA	65.0	80.0	45.0
CA19-9	62.5	80.0	42.5
Heteroploid cells	77.5	76.7	54.2
CA125+Heteroploid cells	85.0	86.7	71.7
CA125+CEA	72.5	80.0	52.5
CA125+CA19-9	72.5	83.3	55.8
CEA+Heteroploid cells	82.5	73.3	55.8
CEA+CA19-9	80.0	73.3	53.3
CA19-9+Heteroploid cells	70.0	86.6	56.7

Figure 2 ROC of tumor markers and heteroploid cells in the diagnosis of PC in gastrointestinal cancer patients.