Management of hepatocellular carcinoma: Predictive value of immunohistochemical markers for postoperative survival

Table 1 Immunohistochemical markers of hepatocellular carcinoma associated with prognosis in this review

Marker	Association with poor prognosis	Quoted literature examples
Tumor suppressors
Mutant p53	Increased expression	Schöniger-Hekele et al[18]
Proliferation associated proteins
Ki67 (detected by Mib1)	Increased expression	Schmilovitz-Weiss et al[40]
Proteins associated with angiogenesis
CD105	Increased microvessel density	Yao et al[57]
Proteins involved in angiogenesis		Tseng et al[11]
VEGF	Increased expression
MMPs (matrix metalloproteinases)
MMP-2 and MMP-9	Increased expression	Xiang et al[74]; Nanashima et al[48]
Molecules involved in cell adhesion
E-Cadherin	Decreased expression	Cho et al[94]
CD44 (CD44s and CD44v6)	Increased expression	Ryu et al[112]; Endo K et al[113]
OPN	Increased expression	Huang et al[130]
Cell cycle regulators
p27 (Kip1)	Decreased expression	Wan et al[137]
DNA-binding nuclear protein
HMGB1	Increased expression	Xiao et al[171]
Cancer stem cells
CD133	Increased expression	Chan et al[188]
EpCAM	Increased expression	Chan et al[188]
CK19	Increased expression	Xu et al[197]
Cell surface proteins
GPC3	Increased expression	Fu et al[211]
mTOR Pathway	Increased expression	Baba et al[223]

VEGF: Vascular endothelial growth factor; MMP-2: Matrix metalloproteinases 2; CD44s: CD44 standard isoform; CD44v6: CD44 variant isoforms; OPN: Osteopontin; HMGB1: High-mobility group box 1 protein; EpCAM: Epithelial cell adhesion molecule; CK19: Cytokeratin19; GPC3: Glypican-3; mTOR: Mammalian target of rapamycin.

Table 2 p53 antibody used in different studies in this review

Ref.	Clone	Source	Dilution	Antigen retrieval	Cut-off value1
Tseng et al[11]	DO-7	DAKO	1:100	Citrate buffer	> 5% nuclear p53 staining
Hu et al[13]	DO-7	DAKO	1:1000	Citrate buffer	> 10% nuclear p53 staining
Kang et al[14]	DO-7	DAKO	1:100	Citrate buffer	> 5% nuclear p53 staining
Stroescu et al[16]	DO-7	DAKO	Not reported	Citrate buffer	< 24% nuclear p53 staining
Sung et al[17]	Bp53-12	Zymed	1:80	Citrate buffer	> 5% nuclear p53 staining
Qin et al[19]	DO-7	DAKO	Not reported	Citrate buffer	≥ 10% nuclear p53 staining
Guo et al[20]	CM1	SDC	1:2000	Citrate buffer	> 5% nuclear p53 staining
Umemura et al[21]	DO-7	DAKO	1:50	Citrate buffer	≥ 10% nuclear p53 staining

¹Immunohistochemical cut-off value indicates the percentage of cells with p53 positively staining nuclei. DAKO: Dako Denmark A/S, Glostrup, Denmark; Zymed: Zymed Lab Inc, CA, United States; SDC: San Diego, CA, United States.

Table 3 Clinicopathological parameters affecting the association between p53 expression and prognosis in this review (n)

Ref.	Number of	Positive rate (%)	HBsAg/HCVAb	Edmondson grade		TNM stage		Tumor size
	patients		positive	I + II	III + IV (1)	I + II	III + IV	≤5 cm	> 5 cm
				Well/moderate/poor (2)
Tseng et al[11]	113	37.1	79/34	84	29 (1)	54	59	Not reported
Hu et al[13]	124	41.9	83/30	20/38/13 (2)		61	63	Not reported
Kang et al[14]	83	96.4	59/8	27	56 (1)	Not reported		57	26
Stroescu et al[16]	47	68	40/0	19	28 (1)	Not reported		20	27
Sung et al[17]	105	19	82/6	78	27 (1)	Not reported		> 3 cm	52
Qin et al[19]	113	22	40/25	55	58 (1)	Not reported		48	55
Guo et al[20]	104	34.6	14/55	18/56/31 (2)		67	37	Not reported
Umemura et al[21]	90	33.3	Not reported	65	25 (1)	Not reported		37	53

TNM: Tumor-node-metastasis; HBsAg: Hepatitis B surface antigen; HCVAb: Hepatitis C virus antibody.