Clinical significance of the expression of isoform 165 vascular endothelial growth factor mRNA in noncancerous liver remnants of patients with hepatocellular carcinoma

Table 1 Characteristics of 60 patients with HCC undergoing curative resection.

Variables	No. of patients (%)
Age (mean, yr) (±SD)	50.4±12.6
Male	44(73)
Cirrhosis	47(78)
Child- Pugh's class A	43(72)
Serum AFP < 20 ng/mL	19(32)
20-103 ng/mL	29(48)
>103 ng/mL	12(20)
HBsAg (+)	47(78)
Anti-HCV (+)	32(53)
Size of HCC <3 cm	17(28)
3-10 cm	22(37)
>10 cm	2(35)
Edmondson-Steiner's grade I	13(22)
Grade II	11(18)
Grade III	18(30)
Grade IV	18(30)
Absent or incomplete capsule	39(65)
Vascular permeation	33(55)
Daughter nodules	31(52)

AFP: serum alpha fetoprotein; HBsAg (+): positive hepatitis B surface antigen; Anti-HCV (+): positive hepatitis C virus antibody; Edmondson Steiner grade: differentiation grade.

Table 2 Comparison of characteristics of primary HCC between different levels of VEGF₁₆₅ mRNA in noncancerous liver tussues.

Characteristics	Group A (%) (n = 49)	Group B (%) (n = 11)	P
Age (yr, mean)	52	48	NS
Male	73.5	72.7	NS
Liver cirrhosis	79.6	72.7	NS
Child-Pugh class A	71.4	72.7	NS
Tumor size <3 cm	28.6	27.2	NS
>10 cm	34.7	36.4	NS
HBsAg (+)	79.6	72.7	NS
Anti-HCV (+)	53.1	54.5	NS
AFP <20 ng/mL	32.7	27.2	NS
>1000 ng/mL	20.4	18.2	NS
Edmondson-Steiner grade I1	10.2	72.7	0.009
Capsule incomplete or absent2	75.5	18.2	0.007
Daughter nodules3	61.2	9.1	0.001
Vascular permeation4	65.3	9.1	0.001

Notes: high VEGF₁₆₅ mRNA: ≥0.500 (group A); low VEGF₁₆₅ mRNA: <0.500 (group B). P: by univariate analysis. 1, 2, 3 and 4: the significant variables in multivariate analysis with P values of 0.036, 0.048, 0.024, and 0.019 respectively. HBsAg: hepatitis B surface antigen; Anti-HCV: antibody to hepatitis C virus; AFP: alpha-fetoprotein; NS: no statistical significance.

Table 3 Correlation between VEGF₁₆₅ mRNA expression in liver remnant and the outcome of patients with HCC.

Outcome	Group A (%) (n = 49)	Group B (%) (n = 11)	P
Recurrence (number; %)	14(28.6)	2(18.2)	0.039
Death1 (number; %)	13(26.5)	1(9.1)	0.048
Recurrence-free interval (median, mo)	8.5	43	0.037
Duration of survival (median, mo)	11.5	41.5	0.04

Notes: high VEGF₁₆₅ mRNA: ≥0.500 (group A), low VEGF₁₆₅ mRNA: <0.500 (group B), death1: patients died of HCC recurrence.

Table 4 Factors influencing tumor recurrence and death of patients in multivariate analysis.

Variables	P	OR
Recurrence
Vascular permeation	0.022	5.36
Daughter nodules	0.033	4.18
Cellular dedifferentiation	0.033	4.18
Incomplete or absent capsule	0.037	3.1
Higher VEGF165 mRNA in liver remnant	0.039	2.29
Death
Vascular permeation	0.012	8.35
Higher VEGF165 mRNA in liver remnant	0.048	2.38

OR: odds ratio; higher VEGF₁₆₅ mRNA: value ≥0.500.

Table 5 Correlation between the clinical features of recurrent hepatocellular carcinoma and the expression of VEGF₁₆₅ mRNA in primary lesions.

Clinical features	VEGF165 mRNA		P
	high (n = 14)	low (n = 2)
Extent of recurrent tumors:
Extrahepatic metastasis (number, %)	8(57.1)	1(50.0)	NS
Multiple recurrent tumors (number, %)	10(71.4)	1(50.0)	0.043
Involvement over two-segments (number, %)	10(71.4)	1(50.0)	0.043
Survival after recurrence (median mo)	4.4	11	0.048
Treatment for recurrent tumors
Surgery (number)	0	0	NS
Non-surgical treatment1 (number, %)	8(57.1)	1(50.0)	NS
No treatment (number, %)	6(42.9)	1(50.0)	NS

Notes: NS: no statistical significance; non-surgical treatments1: treatment with transcatheter arterial chemoembolization or/and percutaneous ethanol injection. High VEGF₁₆₅ mRNA: ≥0.500; low VEGF₁₆₅ mRNA: <0.500.