Multivariate analyses of prognostic factors in hepatocellular carcinoma patients.

<p>Abbreviations<i>:</i> S.E., Standard error; H.R., Hazard ratio; C.I., Confidence interval; M, male; F, female; AFP,</p><p>α-fetoprotein; ETR, early tumor recurrent; P, presence; N, absence; L: low; H: high.</p

Univariate analysis of S100P protein expression with various clinicopathological features and aberrant gene expression in 305 patients with surgically removed unifocal primary hepatocellular carcinoma.

<p>Univariate analysis of S100P protein expression with various clinicopathological features and aberrant gene expression in 305 patients with surgically removed unifocal primary hepatocellular carcinoma.</p

Expression of S100P in HCC and non-cancerous liver parenchyma.

<p>(A) No immunostaining of S100P in non-cancerous liver parenchyma. (B and C) Heterogeneous and diffuse expression of S100P in HCC. (D) The expression of S100P was more prominent at the periphery of the tumor mass near the tumor capsule. (E) Strong expression of S100P in satellite nodules. (F) A portal vein tumor embolus exhibiting strong S100P expression. T: tumor, C: capsule, S: satellite nodule, PVT: portal vein tumor embolus.</p

Identification and confirmation of overexpression of S100P in HCC.

<p>(A) Differential display showed that S100P expression was upregulated in high-stage HCCs. The arrows indicate bands of S100P, which was confirmed by subsequent cloning and sequencing. T: hepatocellular carcinoma; L: non-cancerous liver parenchyma. (B) Expression of S100P mRNA in paired HCC (T) and non-cancerous liver parenchyma (N). RT-PCR measurement identified S100P overexpression in 3 of 6 HCC specimens.</p

Univariate analysis of clinicopathological variables and S100P protein expression with early tumor recurrence (ETR) in patients with surgical removed unifocal primary hepatocellular carcinoma.

<p>Univariate analysis of clinicopathological variables and S100P protein expression with early tumor recurrence (ETR) in patients with surgical removed unifocal primary hepatocellular carcinoma.</p

Interaction between S100P expression with <i>p53</i> mutation or <i>β-catenin</i> mutation in the tumor progression of hepatocellular carcinoma.

<p>Abbreviations: NS, not significant; ETR, early tumor recurrence.</p>†<p>Tumor recurrence within 12 months after hepatectomy.</p><p>a, b, c, d, e, f, g and h designate comparison between the indicated two groups.</p><p><i>P</i> values: ^a0.000001; ^b0.00006; ^c0.0006; ^d0.00068; ^e0.0288; ^f0.000004; ^g0.0015; ^h0.0457.</p

Kaplan–Meier analysis of overall survival in 305 patients with HCC.

<p>(A) The expression of S100P protein in HCC tumor cells was associated with a significantly lower 5-year survival rate than that of HCC tumors in which the S100P protein was not expressed. (B) Patients with S100P-positive, <i>p53</i>-mutated HCCs had a lower 5-year survival rate than the other groups. (C) Patients with S100P-positive, <i>β-catenin</i>-wild type HCCs had the lower 5-year survival rate than the other groups. (D) High tumor stage and concurrent S100P expression in HCC patients were associated with the lower 5-year survival than that of HCC patients with high stage but S100P negative tumors. (E) ETR and concurrent S100P expression in HCC patients were associated with lower 5-year survival than that of HCC patients with ETR but S100P negative tumors. (+): The presence of S100P expression, p53 mutation, β-catenin mutation, high tumor stage, or ETR. (−): The absence of S100P expression, p53 mutation, β-catenin mutation, high tumor stage, or ETR.</p

Univariate analysis of CA-IX protein expression with various clinical and pathological features in 227 patients with surgically resectable primary hepatocellular carcinoma.

<p>Univariate analysis of CA-IX protein expression with various clinical and pathological features in 227 patients with surgically resectable primary hepatocellular carcinoma.</p

Kaplan–Meier analyses of 5-year disease free survival (DFS) and 5-year overall survival (OS) in 227 patients with HCC.

<p>(A and B) The HCCs with CA-IX protein expression correlated with significantly lower DFS and OS than the HCCs without CA-IX protein expression (<i>P</i> = 0.0001 and <i>P</i><1x10^-6, respectively). (C and D) The combinatorial analyses revealed that CA-IX-positive high-stage HCCs had the lowest DFS (<i>P</i><1 x10^-6) and OF (<i>P</i><1x10^-6), which were lower than CA-IX negative high-stage HCCs (<i>P</i> = 0.0004 and <i>P</i><1x10^-6, respectively). However, there were no differences concerning both DFS and OS in low-stage HCCs regardless presence or absence of CA-IX expression. (E and F) The female patients presenting with high-stage HCCs exhibited the lowest DFS (<i>P</i><1 x 10^-6) and OS (<i>P</i><1x10^-6), which were lower than male patients presenting with high-stage HCCs (<i>P</i> = 0.0214 and <i>P</i> = 0.0188, respectively). However, there were no differences concerning DFS and OS in male and female patients with low-stage HCCs. (+): The presence of CA-IX protein expression. (-): The absence of CA-IX expression.</p

Expression of CA-IX protein in non-cancerous liver parenchyma and HCC.

<p>(A and C) Immunohistochemical staining showed heterogeneous and diffuse membranous/cytoplasmic expression of CA-IX in HCC. (E) In the region of tumor necrosis, the viable tumor cells surrounding the necrotic area (<i>N</i>) exhibited strong CA-IX expression. (B, D, F) B, D, and F were the nontumorous counterpart of A, C, and E, respectively. They exhibited strong staining in the bile duct epithelial cells in the portal area but not in the hepatocytes or the mesenchymal cells. A-F x200 (original magnification).</p