Keratin 19-expressing hepatocellular carcinoma and small-duct type intrahepatic cholangiocarcinoma show a similar postoperative clinical course but have distinct genetic features.

Abstract

AIMS:

The present study aimed to systematically compare clinicopathological and genetic features between keratin 19 (K19)-expressing hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA).

METHODS AND RESULTS:

Consecutive cases of HCC (n = 430) were classified into K19+ and K19- using immunohistochemistry. ICCA cases were also separated into small-(S-iCCA; n = 36) and large-duct types (n = 22) based on recently proposed criteria, with the former being used in the present study. Mutational hot-spots in TERT, CTNNB1, KRAS and IDH1 were sequenced. Twenty-six cases (6%) of HCC expressed K19. K19+ HCC was more strongly associated with chronic hepatitis B than K19- HCC and S-iCCA (46% versus 17% and 6%; both P < 0.001). Lymph node metastasis was observed in K19+ HCC (8%) and S-iCCA (22%), but was exceptional in K19- HCC (1%). K19+ HCC had TERT promoter mutations less frequently than K19- HCC (31% versus 59%; P = 0.022), and lacked alterations in KRAS and IDH1. CTNNB1 mutations were similarly observed in K19+ and K19- HCC (23% and 19%, respectively), but rare in S-iCCA (3%). The postoperative survival curve of K19+ HCC was almost identical to that of S-iCCA in the first 5 years (approximately 50% at 5 years), and significantly worse than that of K19- HCC (P = 0.040). Extrahepatic recurrence was more common in K19+ HCC (50%) and S-iCCA (35%) than in K19- HCC (15%) (P = 0.001).

CONCLUSIONS:

Although K19+ HCC and S-iCCA showed similar biological behaviours, they did not share any driver gene mutations, suggesting the possible involvement of epigenetic alterations in the iCCA-like features of K19+ HCC.

• Authors: Masayuki Akita, Tetsuo Ajiki, Takumi Fukumoto, Tomoo Itoh, Yoh Zen
• Journal: Histopathology (Histopathology) Vol. 75 Issue 3 Pg. 385-393 (Sep 2019) ISSN: 1365-2559 [Electronic] England
• PMID: 31017316 (Publication Type: Journal Article)
• Copyright: © 2019 John Wiley & Sons Ltd.

Chemical References

• KRT19 protein, human
• Keratin-19

Topics

• Adult
• Aged
• Aged, 80 and over
• Bile Duct Neoplasms (genetics, metabolism, pathology)
• Carcinoma, Hepatocellular (genetics, metabolism, pathology)
• Cholangiocarcinoma (genetics, metabolism, pathology)
• Female
• Humans
• Keratin-19 (biosynthesis)
• Liver Neoplasms (genetics, metabolism, pathology)
• Male
• Middle Aged
• Survival Analysis