Clinicopathological significance of 'subtypes with stem-cell feature' in combined hepatocellular-cholangiocarcinoma.
OBJECTIVE
Combined hepatocellular-cholangiocarcinoma (cHC-CC), a malignant liver tumour with poor prognosis, is composed of hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and diverse components with intermediate features between HCC and CC, which correspond to hepatic progenitor cells. According to the WHO classification 2010, we surveyed the prevalence and clinicopathological significance of each subtype with stem-cell features [SC subtype; typical subtype (TS), intermediate cell subtype (INT) and cholangiolocellular type (CLC)] in cHC-CC and HCC.


METHODS
Sixty-two patients with cHC-CC (19 women and 43 men) and 26 patients with HCC (all men) were examined. The prevalence of each component was histologically assessed with assistance of mucin and immunohistochemical stainings.


RESULTS
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, 10 (16.1%); INT, 53 (83.9%) and CLC, 44 (71.0%). The proportion of INT was significantly correlated with gender (female-dominant) (P < 0.05), tumour size (P < 0.05), histological grading of HCC (P < 0.01) and inversely correlated with the degree of stromal fibrosis (P < 0.05). The proportion of CLC was significantly correlated with the degree of fibrosis (P < 0.01) and inflammation (P < 0.01), and inversely correlated with tumour size (P < 0.01) and histological grading of HCC (P < 0.05). The proportion of TS was significantly inversely correlated with the degree of inflammation (P < 0.01). Histological diversity score was significantly correlated with vascular invasion and the positivity for α-foetoprotein.


CONCLUSIONS
The proportion of each SC subtype was significantly associated with certain clinicopathological factors, suggesting different properties of each SC subtypes.
Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
Motoko
M
Sasaki
Hirohide
H
Sato
Yuko
Y
Kakuda
Yasunori
Y
Sato
Joon Hyuk
JH
Choi
Yasuni
Y
Nakanuma
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000473:pathology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D018281:Cholangiocarcinoma / Q000473:pathology*; D005260:Female; D005355:Fibrosis; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D008099:Liver / Q000473:pathology*; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000473:pathology; D012189:Retrospective Studies
cholangiolocellular carcinoma; classical type; combined hepatocellular and cholangiocarcinoma; subtypes with stem-cell features