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JPTM > Ahead-of Print

doi: https://doi.org/10.4132/jptm.2017.11.13    [Epub ahead of print]
The Clinicopathological and Prognostic Significance of the Gross Classification of Hepatocellular Carcinoma
Yangkyu Lee1, Hyunjin Park2, Hyejung Lee2, Jai Young Cho3, Yoo-Seok Yoon3, Young-Rok Choi3, Ho-Seong Han3, Eun Sun Jang4, Jin-Wook Kim4, Sook-Hyang Jeong4, Soomin Ahn1, Haeryoung Kim2
1Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
2Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
3Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
4Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
Corresponding Author: Haeryoung Kim ,Tel: +82-2-740-8322, Fax: +82-2-765-5600, Email: haeryoung.kim@snu.ac.kr
Received: August 21, 2017;  Revised: October 13, 2017  Accepted: November 12, 2017.  Published online: November 24, 2017.
ABSTRACT

Background:
We aimed to determine the clinicopathological significance of the gross classification of hepatocellular carcinoma (HCC) according to the Korean Liver Cancer Association (KLCA) guidelines. Method: A retrospective analysis was performed on 242 cases of consecutively resected solitary primary HCC between 2003 and 2012 at Seoul National University Bundang Hospital. The gross classification [vaguely nodular (VN), expanding nodular (EN), multinodular confluent (MC), nodular with perinodular extension (NP) and infiltrative (INF)] was reviewed for all cases, and were correlated with various clinicopathological features and the expression status of “stemness”-related (CK19, EpCAM) and epithelial-mesenchymal transition (EMT)-related (uPAR, Ezrin) markers. Result: Significant differences were seen in overall survival (p=0.015) and disease-free survival (p=0.034) according to the gross classification; INF type showed the worst prognosis while VN and EN-types were more favorable. When the gross types were simplified into 2 groups, type 2 HCCs (MC/NP/INF) were more frequently larger and poorly differentiated, and showed more frequent microvascular and portal venous invasion, intratumoral fibrous stroma and higher pT stages compared to type 1 HCCs (EN/VN) (p<0.05, all). CK19, EpCAM, uPAR and ezrin expression was more frequently seen in type 2 HCCs (p<0.05, all). Gross classification was an independent predictor of both overall and disease-free survival by multivariate analysis (overall survival [p=0.030, hazard ratio 4.118 (95% confidence interval 1.142-14.844)], disease-free survival [p=0.016, hazard ratio 1.617 (95% confidence interval 1.092-2.394)]).
Conclusion:
The gross classification of HCC had significant prognostic value and type 2 HCCs were associated with clinicopathological features of aggressive behavior, increased expression of “stemness”- and EMT-related markers, and decreased survival.
Key Words: Hepatocellular carcinoma, Gross classification, Prognosis