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Clinicopathologic Correlations of E-cadherin and Prrx-1 Expression Loss in Hepatocellular Carcinoma
이기종,김현성,정유민,안혜인,심종민,위영찬,표주연,송영수,백승삼,오영하 대한병리학회 2016 Journal of Pathology and Translational Medicine Vol.50 No.5
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.
High MicroRNA-370 Expression Correlates with Tumor Progression and Poor Prognosis in Breast Cancer
심종민,안혜인,rehman abdul,김현성,이기종,정유민,정민성,백승삼,송영수,장기석 한국유방암학회 2015 Journal of breast cancer Vol.18 No.4
Purpose: Deregulation of microRNA-370 (miR-370) has been reported in various cancers, in which it can act as either an oncogene or a tumor suppressor gene. However, the clinicopathologic significance of miR-370 expression in breast cancer has not been studied. Methods: The expression of miR-370 was determined with quantitative real-time polymerase chain reaction in 60 formalin-fixed, paraffin-embedded primary breast cancer tissues. Additionally, the protein expression levels of previously known targets of miR-370, such as FOXM1, FOXO1, and FOXO3a, were detected using immunohistochemistry. Finally, we analyzed its correlation with target protein expression, clinicopathologic features, and clinical outcome. Results: High levels of miR-370 expression correlated with lymph node metastasis (p=0.009), advanced stage (p=0.002), and frequent perineural invasion (p=0.042). Moreover, patients with high miR-370 expression had poor disease-free survival compared with the lowexpression group. However, no correlation was observed between miR-370 and its target protein expression. Conclusion: Our results indicate that upregulation of miR-370 in breast cancer is correlated with breast cancer progression and that it might be a potential biomarker for predicting clinical outcomes.
김현성,장세민,안혜인,심종민,이기종,정유민,Hulin Han,Abdul Rehman,정민성,장기석,백승삼 한국유방암학회 2015 Journal of breast cancer Vol.18 No.1
Purpose: Dual-specificity protein phosphatase 4 (DUSP4), alsoknown as mitogen-activated protein kinase phosphatase (MKP) 2is a member of the inducible nuclear MKP group. The role ofDUSP4 in cancer development and progression appears to varywith the type of malignancy. The purpose of this study was to investigateDUSP4 expression in a case series of invasive ductalcarcinoma of the breast. Methods: We constructed tissue microarraysconsisting of 16, 14, 47, and 266 cases of normal breast tissue,usual ductal hyperplasia, ductal carcinoma in situ, and invasiveductal carcinoma, respectively. DUSP4 expression was investigatedby immunohistochemistry. Results: Cytoplasmic DUSP4expression was observed. DUSP4 was more frequently expressedin malignant than in benign cases (p=0.024). The mean DUSP4expression score was significantly higher in malignant tumors thanin benign lesions (p=0.019). DUSP4 expression was significantlycorrelated with a larger tumor size (>2 cm, p=0.015). There wasno significant correlation between overall survival or disease-freesurvival and DUSP4 expression in all 266 patients. We evaluatedthe impact of DUSP4 expression on the survival of 120 patientswith T1-stage tumors. Interestingly, Kaplan-Meier survival curvesrevealed that DUSP4 expression had a significant effect on bothoverall patient survival (p=0.034, log-rank test) and disease-freesurvival (p=0.045, log-rank test). In early T-stage breast cancer,DUSP4 expression was associated with a worse prognosis. Conclusion:DUSP4 is frequently upregulated in breast malignancy,and may play an important role in cancer development and progression. In addition, it may be a marker of adverse prognosis, especiallyin patients with early T1-stage cancer.