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Erschienen in: World Journal of Surgery 3/2013

01.03.2013

Low Expression of PAI-2 as a Novel Marker of Portal Vein Tumor Thrombosis and Poor Prognosis in Hepatocellular Carcinoma

verfasst von: Li Zhou, Ye Jin, Quan-Cai Cui, Ke-Min Jin, Wei-Xun Zhou, Bao-Cai Xing

Erschienen in: World Journal of Surgery | Ausgabe 3/2013

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Abstract

Background

Plasminogen activator inhibitor (PAI)-2 was previously shown to be less frequently expressed in hepatocellular carcinoma (HCC). The present study was designed to investigate the clinical, pathological, and prognostic significance of PAI-2 expression in HCC.

Methods

Expression of PAI-2 was detected immunohistochemically for specimens from 78 patients with HCC after hepatic resection and correlated with clinicopathological features and patient survival. Risk factors of portal vein tumor thrombosis (PVTT) were also analyzed.

Results

Positive PAI-2 staining was observed in tumor and non-tumor tissues from 21 (26.9 %) and 56 (71.8 %) patients, respectively. Plasminogen activator inhibitor-2 negativity in tumor tissues was significantly associated with PVTT, with a high sensitivity not only in univariate analysis but also in multivariate analysis. In addition, positive PAI-2 staining was related to smaller tumor size and prolonged patient survival. The Cox regression model identified intratumoral PAI-2 staining as an independent prognosticator in patients with HCC after resection.

Conclusions

Our data demonstrated that low expression of PAI-2 serves as a novel marker of PVTT and poor prognosis in HCC.
Literatur
1.
Zurück zum Zitat Parkin DM, Pisani P, Ferlay J (1993) Estimates of the worldwide incidence of eighteen major cancers in 1985. Int J Cancer 54:594–606PubMedCrossRef Parkin DM, Pisani P, Ferlay J (1993) Estimates of the worldwide incidence of eighteen major cancers in 1985. Int J Cancer 54:594–606PubMedCrossRef
2.
Zurück zum Zitat Pisani P, Parkin DM, Bray F et al (1999) Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer 83:18–29PubMedCrossRef Pisani P, Parkin DM, Bray F et al (1999) Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer 83:18–29PubMedCrossRef
3.
Zurück zum Zitat Parkin DM, Bray F, Ferlay J et al (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108PubMedCrossRef Parkin DM, Bray F, Ferlay J et al (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108PubMedCrossRef
4.
Zurück zum Zitat Zhang XF, Meng B, Qi X et al (2009) Prognostic factors after liver resection for hepatocellular carcinoma with hepatitis B virus-related cirrhosis: surgeon’s role in survival. Eur J Surg Oncol 35:622–628PubMedCrossRef Zhang XF, Meng B, Qi X et al (2009) Prognostic factors after liver resection for hepatocellular carcinoma with hepatitis B virus-related cirrhosis: surgeon’s role in survival. Eur J Surg Oncol 35:622–628PubMedCrossRef
5.
Zurück zum Zitat Lam VW, Ng KK, Chok KS et al (2008) Risk factors and prognostic factors of local recurrence after radiofrequency ablation of hepatocellular carcinoma. J Am Coll Surg 207:20–29PubMedCrossRef Lam VW, Ng KK, Chok KS et al (2008) Risk factors and prognostic factors of local recurrence after radiofrequency ablation of hepatocellular carcinoma. J Am Coll Surg 207:20–29PubMedCrossRef
6.
Zurück zum Zitat Thuluvath PJ, Maheshwari A, Thuluvath NP et al (2009) Survival after liver transplantation for hepatocellular carcinoma in the model for end-stage liver disease and pre-model for end-stage liver disease eras and the independent impact of hepatitis C virus. Liver Transpl 15:754–762PubMedCrossRef Thuluvath PJ, Maheshwari A, Thuluvath NP et al (2009) Survival after liver transplantation for hepatocellular carcinoma in the model for end-stage liver disease and pre-model for end-stage liver disease eras and the independent impact of hepatitis C virus. Liver Transpl 15:754–762PubMedCrossRef
7.
Zurück zum Zitat Tandon P, Garcia-Tsao G (2009) Prognostic indicators in hepatocellular carcinoma: a systematic review of 72 studies. Liver Int 29:502–510PubMedCrossRef Tandon P, Garcia-Tsao G (2009) Prognostic indicators in hepatocellular carcinoma: a systematic review of 72 studies. Liver Int 29:502–510PubMedCrossRef
8.
Zurück zum Zitat Itoh T, Hayashi Y, Kanamaru T et al (2000) Clinical significance of urokinase-type plasminogen activator activity in hepatocellular carcinoma. J Gastroenterol Hepatol 15:422–430PubMedCrossRef Itoh T, Hayashi Y, Kanamaru T et al (2000) Clinical significance of urokinase-type plasminogen activator activity in hepatocellular carcinoma. J Gastroenterol Hepatol 15:422–430PubMedCrossRef
9.
Zurück zum Zitat Wong N, Yeo W, Wong WL et al (2009) TOP2A overexpression in hepatocellular carcinoma correlates with early age onset, shorter patient survival and chemoresistance. Int J Cancer 124:644–652PubMedCrossRef Wong N, Yeo W, Wong WL et al (2009) TOP2A overexpression in hepatocellular carcinoma correlates with early age onset, shorter patient survival and chemoresistance. Int J Cancer 124:644–652PubMedCrossRef
10.
Zurück zum Zitat Ke AW, Shi GM, Zhou J et al (2009) Role of overexpression of CD151 and/or c-Met in predicting prognosis of hepatocellular carcinoma. Hepatology 49:491–503PubMedCrossRef Ke AW, Shi GM, Zhou J et al (2009) Role of overexpression of CD151 and/or c-Met in predicting prognosis of hepatocellular carcinoma. Hepatology 49:491–503PubMedCrossRef
12.
Zurück zum Zitat Dass K, Ahmad A, Azmi AS et al (2008) Evolving role of uPA/uPAR system in human cancers. Cancer Treat Rev 34:122–136PubMedCrossRef Dass K, Ahmad A, Azmi AS et al (2008) Evolving role of uPA/uPAR system in human cancers. Cancer Treat Rev 34:122–136PubMedCrossRef
13.
Zurück zum Zitat Croucher DR, Saunders DN, Lobov S et al (2008) Revisiting the biological roles of PAI2 (SERPINB2) in cancer. Nat Rev Cancer 8:535–545PubMedCrossRef Croucher DR, Saunders DN, Lobov S et al (2008) Revisiting the biological roles of PAI2 (SERPINB2) in cancer. Nat Rev Cancer 8:535–545PubMedCrossRef
14.
Zurück zum Zitat Nordengren J, Fredstorp Lidebring M et al (2002) High tumor tissue concentration of plasminogen activator inhibitor 2 (PAI-2) is an independent marker for shorter progression-free survival in patients with early stage endometrial cancer. Int J Cancer 97:379–385PubMedCrossRef Nordengren J, Fredstorp Lidebring M et al (2002) High tumor tissue concentration of plasminogen activator inhibitor 2 (PAI-2) is an independent marker for shorter progression-free survival in patients with early stage endometrial cancer. Int J Cancer 97:379–385PubMedCrossRef
15.
Zurück zum Zitat Champelovier P, Boucard N, Levacher G et al (2002) Plasminogen- and colony-stimulating factor-1-associated markers in bladder carcinoma: diagnostic value of urokinase plasminogen activator receptor and plasminogen activator inhibitor type-2 using immunocytochemical analysis. Urol Res 30:301–309PubMedCrossRef Champelovier P, Boucard N, Levacher G et al (2002) Plasminogen- and colony-stimulating factor-1-associated markers in bladder carcinoma: diagnostic value of urokinase plasminogen activator receptor and plasminogen activator inhibitor type-2 using immunocytochemical analysis. Urol Res 30:301–309PubMedCrossRef
16.
Zurück zum Zitat Meijer-van Gelder ME, Look MP, Peters HA et al (2004) Urokinase-type plasminogen activator system in breast cancer: association with tamoxifen therapy in recurrent disease. Cancer Res 64:4563–4568PubMedCrossRef Meijer-van Gelder ME, Look MP, Peters HA et al (2004) Urokinase-type plasminogen activator system in breast cancer: association with tamoxifen therapy in recurrent disease. Cancer Res 64:4563–4568PubMedCrossRef
17.
Zurück zum Zitat Smith R, Xue A, Gill A et al (2007) High expression of plasminogen activator inhibitor-2 (PAI-2) is a predictor of improved survival in patients with pancreatic adenocarcinoma. World J Surg 31:493–502. doi:10.1007/s00268-006-0289-9 PubMedCrossRef Smith R, Xue A, Gill A et al (2007) High expression of plasminogen activator inhibitor-2 (PAI-2) is a predictor of improved survival in patients with pancreatic adenocarcinoma. World J Surg 31:493–502. doi:10.​1007/​s00268-006-0289-9 PubMedCrossRef
18.
Zurück zum Zitat Zhou L, Hayashi Y, Itoh T et al (2000) Expression of urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor, and plasminogen activator inhibitor-1 and -2 in hepatocellular carcinoma. Pathol Int 50:392–397PubMedCrossRef Zhou L, Hayashi Y, Itoh T et al (2000) Expression of urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor, and plasminogen activator inhibitor-1 and -2 in hepatocellular carcinoma. Pathol Int 50:392–397PubMedCrossRef
19.
Zurück zum Zitat Edmondson HA, Steiner PE (1954) Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer 7:462–503PubMedCrossRef Edmondson HA, Steiner PE (1954) Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer 7:462–503PubMedCrossRef
20.
Zurück zum Zitat Hasina R, Hulett K, Bicciato S et al (2003) Plasminogen activator inhibitor-2: a molecular biomarker for head and neck cancer progression. Cancer Res 63:555–559PubMed Hasina R, Hulett K, Bicciato S et al (2003) Plasminogen activator inhibitor-2: a molecular biomarker for head and neck cancer progression. Cancer Res 63:555–559PubMed
21.
Zurück zum Zitat Kaibori M, Ishizaki M, Matsui K et al (2010) Predictors of microvascular invasion before hepatectomy for hepatocellular carcinoma. J Surg Oncol 102:462–468PubMedCrossRef Kaibori M, Ishizaki M, Matsui K et al (2010) Predictors of microvascular invasion before hepatectomy for hepatocellular carcinoma. J Surg Oncol 102:462–468PubMedCrossRef
22.
Zurück zum Zitat Kim SJ, Lee KK, Kim DG (2010) Tumor size predicts the biological behavior and influence of operative modalities in hepatocellular carcinoma. Hepatogastroenterology 57:121–126PubMed Kim SJ, Lee KK, Kim DG (2010) Tumor size predicts the biological behavior and influence of operative modalities in hepatocellular carcinoma. Hepatogastroenterology 57:121–126PubMed
23.
Zurück zum Zitat Wang T, Hu HS, Feng YX et al (2010) Characterisation of a novel cell line (CSQT-2) with high metastatic activity derived from portal vein tumour thrombus of hepatocellular carcinoma. Br J Cancer 102:1618–1626PubMedCrossRef Wang T, Hu HS, Feng YX et al (2010) Characterisation of a novel cell line (CSQT-2) with high metastatic activity derived from portal vein tumour thrombus of hepatocellular carcinoma. Br J Cancer 102:1618–1626PubMedCrossRef
24.
Zurück zum Zitat Zhou L, Rui JA, Wang SB et al (2006) Clinicopathological features, post-surgical survival and prognostic indicators of elderly patients with hepatocellular carcinoma. Eur J Surg Oncol 32:767–772PubMedCrossRef Zhou L, Rui JA, Wang SB et al (2006) Clinicopathological features, post-surgical survival and prognostic indicators of elderly patients with hepatocellular carcinoma. Eur J Surg Oncol 32:767–772PubMedCrossRef
25.
Zurück zum Zitat Darnell GA, Antalis TM, Johnstone RW et al (2003) Inhibition of retinoblastoma protein degradation by interaction with the serpin plasminogen activator inhibitor 2 via a novel consensus motif. Mol Cell Biol 23:6520–6532PubMedCrossRef Darnell GA, Antalis TM, Johnstone RW et al (2003) Inhibition of retinoblastoma protein degradation by interaction with the serpin plasminogen activator inhibitor 2 via a novel consensus motif. Mol Cell Biol 23:6520–6532PubMedCrossRef
26.
Zurück zum Zitat Takahashi C, Ewen ME (2006) Genetic interaction between Rb and N-ras: differentiation control and metastasis. Cancer Res 66:9345–9348PubMedCrossRef Takahashi C, Ewen ME (2006) Genetic interaction between Rb and N-ras: differentiation control and metastasis. Cancer Res 66:9345–9348PubMedCrossRef
27.
Zurück zum Zitat Arima Y, Inoue Y, Shibata T et al (2008) Rb depletion results in deregulation of E-cadherin and induction of cellular phenotypic changes that are characteristic of the epithelial-to-mesenchymal transition. Cancer Res 68:5104–5112PubMedCrossRef Arima Y, Inoue Y, Shibata T et al (2008) Rb depletion results in deregulation of E-cadherin and induction of cellular phenotypic changes that are characteristic of the epithelial-to-mesenchymal transition. Cancer Res 68:5104–5112PubMedCrossRef
28.
Zurück zum Zitat De Petro G, Tavian D, Copeta A et al (1998) Expression of urokinase-type plasminogen activator (u-PA), u-PA receptor, and tissue-type PA messenger RNAs in human hepatocellular carcinoma. Cancer Res 58:2234–2239PubMed De Petro G, Tavian D, Copeta A et al (1998) Expression of urokinase-type plasminogen activator (u-PA), u-PA receptor, and tissue-type PA messenger RNAs in human hepatocellular carcinoma. Cancer Res 58:2234–2239PubMed
Metadaten
Titel
Low Expression of PAI-2 as a Novel Marker of Portal Vein Tumor Thrombosis and Poor Prognosis in Hepatocellular Carcinoma
verfasst von
Li Zhou
Ye Jin
Quan-Cai Cui
Ke-Min Jin
Wei-Xun Zhou
Bao-Cai Xing
Publikationsdatum
01.03.2013
Verlag
Springer-Verlag
Erschienen in
World Journal of Surgery / Ausgabe 3/2013
Print ISSN: 0364-2313
Elektronische ISSN: 1432-2323
DOI
https://doi.org/10.1007/s00268-012-1866-8

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