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간암의 수술적 절제를 시행한 환자에서 종양 재발 및 생존에 대한 예측 인자로서 EpCAM에 대한 연구

EpCAM as a Predictive Marker of Tumor Recurrence and Survival in Patients Who Underwent Surgical Resection for Hepatocellular Carcinoma

초록/요약

Background/Aims: Epithelial cell adhesion molecule (EpCAM) is expressed in hepatic progenitor cells and hepatocellular carcinoma (HCC), and is considered a marker of liver cancer stem cells. We evaluated the immunohistochemical expression of EpCAM and other stemness-related markers as prognosticators of tumor recurrence and survival in patients who underwent surgical resection for HCC Materials and Methods: A total of 262 patients were enrolled who had undergone surgical resection for HCC, with immunohistochemical staining results for EpCAM. The alpha-fetoprotein (AFP), cytokeratin 19 (CK19), CK7 and glypican-3 expressions were also analyzed in resected tumor specimens via immunohistochemistry. Results: A multivariate Cox regression analysis showed that tumor size [hazard ratio (HR)=2.26, p=0.005], intrahepatic metastasis (HR=2.31, p=0.011), and EpCAM positivity (HR=1.74, p=0.038) were associated with tumor recurrence. In a Kaplan–Meier survival analysis, patients with EpCAM-positive tumors had a significantly higher tumor recurrence rate and a reduced overall survival compared to those with EpCAM-negative tumors. Conclusion: Immunohistochemical expression of EpCAM was identified as a poor prognosticator of recurrence and survival after surgical resection in patients with HCC.

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초록/요약

배경/목적: Epithelial cell adhesion molecule (EpCAM)은 간 전구세포와 간암에서 발현하며, 간암 줄기 세포의 표지자로 알려져 있다. 우리는 간암을 수술적 절제한 환자에서 종양 재발과 생존의 예후 예측 인자로서 EpCAM과 다른 줄기세포관련 표지자의 면역조직화학적 발현을 평가하였다. 방법: 간암을 수술적 절제를 했으면서 EpCAM의 면역조직화학염색 결과가 있는 262명의 환자들이 연구에 등록이 되었다. 알파태아단백, 시토케라틴 19, 시토케라틴17, 글리피칸-3의 발현 또한 절제된 검체에서 면역조직화학 염색을 통해 분석하였다. 결과: 다변량 콕스 희귀분석을 시행한 결과 종양의 크기 (위험비=2.26, p=0.005), 간내 전이 (위험비=2.31, p=0.011)), 그리고 EpCAM양성 (위험비=1.74, p=0.038)이 종양 재발과 관련이 있음을 확인하였다. 카플란-마이어 생존 분석을 시행한 결과 EpCAM양성이 확인된 환자에서 EpCAM음성 환자보다 높은 재발율과 낮은 생존율이 확인되었다. 결론: EpCAM의 면역조직화학적 발현은 간암 환자의 수술적 절제 후 재발과 생존에 나쁜 예후 예측 인자임을 확인하였다.

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목차

Ⅰ. INTRODUCTION 1
Ⅱ. MATERIALS AND METHODS 3
A. Patients 3
B. Samples and pathological data 4
C. IHC staining 4
D. Statistical analysis 5
Ⅲ. RESULTS 7
A. Baseline clinicopathological characteristics 7
B. Factors predictive of HCC recurrence after surgical resection 8
C. Clinicopathological characteristics and outcomes according to IHC expression of EpCAM 9
D. EpCAM and serum AFP level as a predictor of HCC recurrence and survival 12
E. Diagnostic accuracy of EpCAM and serum AFP level as a predictor of HCC recurrence 13
Ⅳ. DISCUSSION 15
Ⅴ. CONCLUSION 19
REFERENCES 20
국문 요약 25

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