Prevalence and Significance of “Subtypes with Stem-Cell Feature” in Combined Hepatocellular-Cholangiocarcinoma and Hepatocellular Carcinoma
Motoko Sasaki, Hirohide Sato, Yasunori Sato, Joon Hyuk Choi, Yasuni Nakanuma. Kanazawa University Graduate School of Medicine, Kanazawa, Japan; Yeungnam University College of Medicine, Daegu, Korea
Background: Combined hepatocellular-cholangiocarcinoma (cHC-CC), a malignant liver tumor with poor prognosis, is composed of hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and diverse components with intermediate features between HCC and CC. According to the WHO classification 2010, we surveyed the prevalence and clinicopathological significance of "subtypes with stem cell features (SC subtype)"; typical subtype (TS), intermediate cell subtype (Int) and cholangiolocellular type (CLC) in cHC-CC and HCC.
Design: Thirty-nine patients with cHC-CC (12 women and 27 men, age ranged 44-77 yrs) and 26 patients with HCC (all men, age ranged 52-86 yrs) were retrieved from our pathological files (1987-2012). The background diseases were hepatitis B (n=15 and 6), hepatitis C (12 and 11), chronic alcoholism (3 and 6) and cryptogenic (9 and 3) in cHC-CC and HCC, respectively. The prevalence of each component (HCC, TS, INT, CLC and CC) was histologically assessed with assistance of mucin staining and immunohistochemical staining for CK7, CK19, EMA, EpCAM, NCAM, AFP and HepPar1. Histological grading of HCC and the extent of stromal fibrosis and inflammation in tumor tissues were also evaluated.
Results: Mucin production was detected in 14 cHC-CCs. SC subtypes were observed in all cHC-CCs in various amount and combination. The prevalence of each SC subtype in cHC-CC was as follows; TS, 7 (17.9%); INT, 33 (84.6%); CLC, 22 (56.4%). The proportion of TS was significantly associated with lower histological grade of coexistent HCC (p<0.01). In contrast, the proportion of INT was associated with higher histological grade of coexistent HCC (p<0.01). The proportion of INT was correlated with tumor size (p<0.01), while the proportion of CLC was inversely correlated with tumor size (p<0.01). The proportion of CLC was associated with AFP expression and the extent of inflammation (p<0.01). The components of TS and CLC were also observed in 6 (23.1%) and 2 (7.7%; all coexist with TS) in HCC, respectively. The proportion of TS in HCC was significantly associated with the extent of stromal fibrosis and inflammation (p<0.01).
Conclusions: The TS was associated with lower histological grade of HCC in cHC-CC. In contrast, the INT was associated with higher histological grade of HCC and bigger tumor size in cHC-CC. The CLC was significantly associated with smaller size, AFP expression and the extent of inflammation. Each SC subtype may have different clinicopathological significances in cHC-CC.
Monday, March 4, 2013 2:45 PM
Proffered Papers: Section E, Monday Afternoon