Prognostic values of chromosome 18q microsatellite alterations in stage II colonic carcinoma

Table 1 Clinical features of patients and survival status after surgery n (%)

Characteristics	Patients	Survival (mo) (mean ± SE)	3-yr overall survival (%)	5-yr overall survival (%)	P value
Gender					0.753
Male	66 (62.3)	104 ± 3	90.7	83.2
Female	40 (37.7)	100 ± 3	91.6	84.1
Age (yr)					0.011
≤ 60	60 (56.6)	107 ± 2	93.5	89.7
> 60	46 (43.4)	97 ± 4	88.0	77.4
Tumor site					0.467
Right colon	47 (44.3)	100 ± 3	89.5	82.9
Left colon	59 (55.7)	104 ± 3	92.2	84.8
Tumor size (cm)					0.213
< 5	48 (45.3)	108 ± 3	93.8	91.8
≥ 5	58 (54.7)	101 ± 3	90.1	80.6
Grade					0.220
Well/moderately differentiated	81 (76.4)	103 ± 2	92.0	85.3
Poorly differentiated	25 (23.6)	104 ± 4	90.7	82.7
Histologic features					0.246
Adenocarcinoma	79 (74.5)	104 ± 2	91.6	83.9
Mucinous	27 (25.5)	101 ± 4	87.6	78.3
pT stage					0.090
T3	63 (59.4)	106 ± 2	93.9	85.8
T4	43 (40.6)	96 ± 4	87.0	78.5
Chemotherapy					0.114
No	18 (17.0)	99 ± 3	83.3	69.8
Yes	88 (83.0)	103 ± 4	90.9	84.8

Table 2 Informative cases, loss of heterozygosity and microsatellite instability (n = 106) n (%)

Marker	Location	Informative cases	LOH (+)	MSI
D18S474	18q21.1	86	26 (30.2)	15 (17.4)
D18S55	18q23	77	18 (23.4)	11 (14.3)
D18S58	18q23	70	20 (28.6)	18 (25.7)
D18S61	18q22.2	80	28 (35.0)	13 (16.3)
D18S64	18q21.3	72	15 (20.8)	10 (13.9)
Overall	18q21-23	102	50 (49.0)	42 (41.2)

LOH: Loss of heterozygosity; MSI: Microsatellite instability.

Table 3 Correlation between loss of heterozygosity at chromosome 18q, microsatellite instability and clinicopathologic variables of patients n (%)

Characteristics	Cases	LOH (+)	LOH (-)	P value	MSI-H (%)	MSI-L/MSS (%)	P value
Gender				0.662			0.272
Male	63 (61.8)	27	36		9	54
Female	39 (38.2)	23	16		9	30
Age (yr)				0.435			0.111
≤ 60	58 (56.9)	32	26		11	47
> 60	44 (43.1)	18	26		7	37
Tumor site				0.023			< 0.001
Right colon	46 (45.1)	13	33		15	31
Left colon	56 (54.9)	37	19		3	53
Tumor size (cm)				0.232			0.327
< 5	48 (47.1)	28	20		8	40
≥ 5	54 (52.9)	22	32		10	44
Grade				0.016			0.047
Well/moderately differentiated	78 (76.5)	34	44		15	63
Poorly differentiated	24 (23.5)	16	8		3	21
Histologic features				0.005			0.004
Adenocarcinoma	77 (75.5)	44	33		5	72
Mucinous	25 (24.5)	6	19		13	12
pT stage				0.126			0.272
T3	61 (59.8)	33	28		11	50
T4	41 (40.2)	17	24		7	34
Chemotherapy				0.650			0.782
No	17 (16.7)	10	7		4	13
Yes	85 (83.3)	40	45		14	71

LOH: Loss of heterozygosity; MSI-L: Low frequency microsatellite instability; MSI-H: High frequency of microsatellite instability; MSS: Microsatellite stable.

Table 4 Five-year overall survival and disease-free survival after surgery in relation to microsatellite alteration in patients with stage II colon cancer

Parameter	Cases	5-yr overall survival (%)	P value	5-yr disease-free survival (%)	P value
18q-LOH			0.019		0.010
(+)	50	71.3		70.5
(-)	52	88.3		87.1
MSI			0.045		0.155
MSI-H	18	94.4		88.5
MSI-L/MSS	84	77.8		76.7

18q-LOH: Loss of heterozygosity at chromosome 18q; MSI: Microsatellite instability; MSI-L: Low frequency MSI; MSI-H: High frequency of MSI; MSS: Microsatellite stable.

Table 5 Five-year overall survival after surgery in relation to each microsatellite locus

Marker	Cases	5-yr overall survival (%)	P value
D18S474	86		0.010
LOH (+)	26	65.2
LOH (-)	60	84.9
D18S55	77		0.504
LOH (+)	18	77.8
LOH (-)	59	81.6
D18S58	70		0.293
LOH (+)	20	71.4
LOH (-)	50	83.3
D18S61	80		0.005
LOH (+)	28	64.3
LOH (-)	52	87.0
D18S64	72		0.076
LOH (+)	15	69.0
LOH (-)	57	86.3

LOH: Loss of heterozygosity.

Table 6 Univariate analysis of prognostic factors for 5-year survival according to Cox’s proportional hazards regression model in patients with stage II colon cancer

Variables	B	SE	Wald value	P value	RR
Age	-0.837	0.404	4.290	0.038	0.433
pT stage	0.667	0.395	2.859	0.091	1.949
Chemotherapy	-0.727	0.443	2.698	0.100	0.483
18q-LOH	0.903	0.425	4.509	0.014	2.467
MSI	1.147	0.736	2.428	0.039	3.149

18q-LOH: Loss of heterozygosity at chromosome 18q; MSI: Microsatellite instability.

Table 7 Multivariate analysis of prognostic factors for 5-year survival according to Cox's proportional hazards regression model in patients with stage II colon cancer

Variables	B	SE	Wald value	P value	RR
18q-LOH	0.985	0.429	5.286	0.021	2.679

18q-LOH: Loss of heterozygosity at chromosome 18q.