Clinicopathologic Correlations of E-cadherin and Prrx-1 Expression Loss in Hepatocellular Carcinoma
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: Developing predictive markers for hepatocellular carcinoma (HCC) is important, because many patients experience recurrence and metastasis. Epithelial to mesenchymal transition (EMT) is a developmental process that plays an important role during embryogenesis and also during cancer metastasis. Paired-related homeobox protein 1 (Prrx-1) is an EMT inducer that has recently been introduced, and its prognostic significance in HCC is largely unknown. Methods: Tissue microarray was constructed using surgically resected primary HCCs from 244 cases. Immunohistochemical staining of E-cadherin and Prrx-1 was performed. The correlation between Ecadherin loss and Prrx-1 expression, as well as other clinicopathologic factors, was evaluated. Results: E-cadherin expression was decreased in 96 cases (39.4%). Loss of E-cadherin correlated with a higher recurrence rate (p < .001) but was not correlated with patient’s survival. Thirty-two cases (13.3%) showed at least focal nuclear Prrx-1 immunoreactivity while all non-neoplastic livers (n = 22) were negative. Prrx-1 expression was not associated with E-cadherin loss, survival or recurrence rates, pathologic factors, or the Ki-67 labeling index. Twenty tumors that were positive for E-cadherin and Prrx-1 had significantly higher nuclear grades than the rest of the cohort (p = .037). In Cox proportional hazard models, E-cadherin loss and large vessel invasion were independent prognostic factors for shorter disease-free survival. Cirrhosis and high Ki-67 index (>40%) were independent prognostic factors for shorter overall survival. Conclusions: Prrx-1 was expressed in small portions of HCCs but not in normal livers. Additional studies with a large number of Prrx-1-positive cases are required to confirm the results of this study.
Abstract
Background: Developing predictive markers for hepatocellular carcinoma (HCC) is important, because many patients experience recurrence and metastasis. Epithelial to mesenchymal transition (EMT) is a developmental process that plays an important role during embryogenesis and also during cancer metastasis. Paired-related homeobox protein 1 (Prrx-1) is an EMT inducer that has recently been introduced, and its prognostic significance in HCC is largely unknown. Methods: Tissue microarray was constructed using surgically resected primary HCCs from 244 cases. Immunohistochemical staining of E-cadherin and Prrx-1 was performed. The correlation between Ecadherin loss and Prrx-1 expression, as well as other clinicopathologic factors, was evaluated. Results: E-cadherin expression was decreased in 96 cases (39.4%). Loss of E-cadherin correlated with a higher recurrence rate (p < .001) but was not correlated with patient’s survival. Thirty-two cases (13.3%) showed at least focal nuclear Prrx-1 immunoreactivity while all non-neoplastic livers (n = 22) were negative. Prrx-1 expression was not associated with E-cadherin loss, survival or recurrence rates, pathologic factors, or the Ki-67 labeling index. Twenty tumors that were positive for E-cadherin and Prrx-1 had significantly higher nuclear grades than the rest of the cohort (p = .037). In Cox proportional hazard models, E-cadherin loss and large vessel invasion were independent prognostic factors for shorter disease-free survival. Cirrhosis and high Ki-67 index (>40%) were independent prognostic factors for shorter overall survival. Conclusions: Prrx-1 was expressed in small portions of HCCs but not in normal livers. Additional studies with a large number of Prrx-1-positive cases are required to confirm the results of this study.
참고문헌 (25)
- 정규원, "Cancer Statistics in Korea: Incidence, Mortality, Survival and Prevalence in 2010", Cancer Research and Treatment, 45(1), pp.1~14 (2013), 대한암학회[DOI]
- Tung-Ping Poon R, "Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma", Ann Surg, 232, pp.10~24 (2000)
- Thiery JP, "Epithelial-mesenchymal transitions in development and disease", Cell, 139, pp.871~890 (2009)
- Hardin H, "The roles of the epithelial-mesenchymal transition marker PRRX1 and miR-146b-5p in papillary thyroid carcinoma progression", Am J Pathol, 184, pp.2342~2354 (2014)
- Ocana OH, "Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1", Cancer Cell, 22, pp.709~724 (2012)
- Reichert M, "The Prrx1 homeodomain transcription factor plays a central role in pancreatic regeneration and carcinogenesis", Genes Dev, 27, pp.288~300 (2013)
- Takahashi Y, "Paired related homoeobox 1, a new EMT inducer, is involved in metastasis and poor prognosis in colorectal cancer", Br J Cancer, 109, pp.307~311 (2013)
- Hirata H, "Downregulation of PRRX1 confers cancer stem cell-like properties and predicts poor prognosis in hepatocellular carcinoma", Ann Surg Oncol, 22(Suppl 3), pp.S1402~S1409 (2015)
- 우현영, "Clinicopathologic significance of the expression of Snail in hepatocellular carcinoma", Clinical and Molecular Hepatology, 17(1), pp.12~18 (2011), 대한간학회
- Schuffler PJ, "TMARKER: A free software toolkit for histopathological cell counting and staining estimation", J Pathol Inform, 4(Suppl), pp.S2~ (2013)
- Nakanishi K, "Akt phosphorylation is a risk factor for early disease recurrence and poor prognosis in hepatocellular carcinoma", Cancer, 103, pp.307~312 (2005)
- Ito Y, "Both cell proliferation and apoptosis significantly predict shortened disease-free survival in hepatocellular carcinoma", Br J Cancer, 81, pp.747~751 (1999)
- Prall F, "Tumour budding in colorectal carcinoma", Histopathology, 50, pp.151~162 (2007)
- Peinado H, "Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype?", Nat Rev Cancer, 7, pp.415~428 (2007)
- Cho SB, "Expression of E- and N-cadherin and clinicopathology in hepatocellular carcinoma", Pathol Int, 58, pp.635~642 (2008)
- Zhang L, "Hypoxia induces epithelial-mesenchymal transition via activation of SNAI1 by hypoxia-inducible factor -1alpha in hepatocellular carcinoma", BMC Cancer, 13, pp.108~ (2013)
- Kwon Ghee Young, "Promoter Methylation of E-cadherin in Hepatocellular Carcinomas and Dysplastic Nodules", Journal of Korean Medical Science, 20(2), pp.242~247 (2005), 대한의학회
- Chen J, "Prognostic significance of E-cadherin expression in hepatocellular carcinoma: a meta-analysis", PLoS One, 9, pp.E103952~ (2014)
- Aoki S, "Prognostic significance of dysadherin expression in advanced colorectal carcinoma", Br J Cancer, 88, pp.726~732 (2003)
- Asgeirsson KS, "Altered expression of E-cadherin in breast cancer. patterns, mechanisms and clinical significance", Eur J Cancer, 36, pp.1098~1106 (2000)
- Zhao XL, "Promotion of hepatocellular carcinoma metastasis through matrix metalloproteinase activation by epithelial-mesenchymal transition regulator Twist1", J Cell Mol Med, 15, pp.691~700 (2011)
- Tannapfel A, "Apoptosis and proliferation in relation to histopathological variables and prognosis in hepatocellular carcinoma", J Pathol, 187, pp.439~445 (1999)
- Tsai JH, "Spatiotemporal regulation of epithelial-mesenchymal transition is essential for squamous cell carcinoma metastasis", Cancer Cell, 22, pp.725~736 (2012)
- Ferrell JE Jr, "The biochemical basis of an all-or-none cell fate switch in Xenopus oocytes", Science, 280, pp.895~898 (1998)
- Batchelor E, "The ups and downs of p53: understanding protein dynamics in single cells", Nat Rev Cancer, 9, pp.371~377 (2009)