Clinicopathologic Correlations of E-cadherin and Prrx-1 Expression Loss in Hepatocellular Carcinoma.
- Author:
Kijong YI
1
;
Hyunsung KIM
;
Yumin CHUNG
;
Hyein AHN
;
Jongmin SIM
;
Young Chan WI
;
Ju Yeon PYO
;
Young Soo SONG
;
Seung Sam PAIK
;
Young Ha OH
Author Information
- Publication Type:Original Article
- Keywords: Liver; Neoplasms; Epithelial-mesenchymal transition; Prrx-1 protein
- MeSH: Cadherins*; Carcinoma, Hepatocellular*; Cohort Studies; Disease-Free Survival; Embryonic Development; Epithelial-Mesenchymal Transition; Female; Fibrosis; Genes, Homeobox; Humans; Liver; Neoplasm Metastasis; Pregnancy; Proportional Hazards Models; Recurrence
- From:Journal of Pathology and Translational Medicine 2016;50(5):327-336
- CountryRepublic of Korea
- Language:English
- 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 E-cadherin 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.