The Clinicopathological and Prognostic Significance of the Gross Classification of Hepatocellular Carcinoma.
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.


METHODS
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 (cytokeratin 19 [CK19], epithelial cell adhesion molecule [EpCAM]), and epithelial-mesenchymal transition (EMT)-related (urokinase plasminogen activator receptor [uPAR] and Ezrin) markers.


RESULTS
Significant differences were seen in overall survival (p=.015) and disease-free survival (p = .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 two 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<.05, all). CK19, EpCAM, uPAR, and ezrin expression was more frequently seen in type 2 HCCs (p<.05, all). Gross classification was an independent predictor of both overall and disease-free survival by multivariate analysis (overall survival: p=.030; hazard ratio, 4.118; 95% confidence interval, 1.142 to 14.844; disease-free survival: p=.016; hazard ratio, 1.617; 95% confidence interval, 1.092 to 2.394).


CONCLUSIONS
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.
['Lee|Yangkyu|Y|', 'Park|Hyunjin|H|', 'Lee|Hyejung|H|', 'Cho|Jai Young|JY|', 'Yoon|Yoo-Seok|YS|', 'Choi|Young-Rok|YR|', 'Han|Ho-Seong|HS|', 'Jang|Eun Sun|ES|', 'Kim|Jin-Wook|JW|', 'Jeong|Sook-Hyang|SH|', 'Ahn|Soomin|S|', 'Kim|Haeryoung|H|']
Gross classification Prognosis Carcinoma, hepatocellular