Journal of Pathology and Translational Medicine (Mar 2018)

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

  • Yangkyu Lee,
  • Hyunjin Park,
  • Hyejung Lee,
  • Jai Young Cho,
  • Yoo-Seok Yoon,
  • Young-Rok Choi,
  • Ho-Seong Han,
  • Eun Sun Jang,
  • Jin-Wook Kim,
  • Sook-Hyang Jeong,
  • Soomin Ahn,
  • Haeryoung Kim

DOI
https://doi.org/10.4132/jptm.2017.11.13
Journal volume & issue
Vol. 52, no. 2
pp. 85 – 92

Abstract

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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.

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