High expression of macrophage colony-stimulating factor-1 receptor in peritumoral liver tissue is associated with poor outcome in hepatocellular carcinoma after curative resection.
BACKGROUND
Macrophage colony-stimulating factor 1 receptor (CSF-1R) expression in hepatocellular carcinoma (HCC) and its prognostic values are unclear. This study evaluated the prognostic values of the intratumoral and peritumoral expression of CSF-1R in HCC patients after curative resection.


METHODS
Tissue microarrays containing material from cohort 1 (105 patients) and cohort 2 (32 patients) were constructed. Immunohistochemistry was performed and prognostic values of these and other clinicopathological data were evaluated. The CSF-1R mRNA level was assessed by quantitative real-time polymerase chain reaction in cohort 3 (52 patients).


RESULTS
Both the CSF-1R density and its mRNA level were significantly higher in peritumoral liver tissue than in the corresponding tumor tissue. CSF-1R was distributed in a gradient in the long-distance peritumoral tissue microarray, with its density decreasing as the distance from the tumor margin increased. High peritumoral CSF-1R was significantly associated with more intrahepatic metastases and poorer survival. Peritumoral CSF-1R was an independent prognostic factor for both overall survival and time to recurrence and affected the incidence of early recurrence. However, intratumoral CSF-1R did not correlate with any clinicopathological feature. Peritumoral CSF-1R was also associated with both overall survival and time to recurrence in a subgroup with small HCCs (< or =5 cm).


CONCLUSIONS
Peritumoral CSF-1R is associated with intrahepatic metastasis, tumor recurrence, and patient survival after hepatectomy, highlighting the critical role of the peritumoral liver milieu in HCC progression. CSF-1R may become a potential therapeutic target for postoperative adjuvant treatment.
Jia
Jin-Bin
JB
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China.
Wang
Wen-Quan
WQ
Sun
Hui-Chuan
HC
Zhu
Xiao-Dong
XD
Liu
Liang
L
Zhuang
Peng-Yuan
PY
Zhang
Ju-Bo
JB
Zhang
Wei
W
Xu
Hua-Xiang
HX
Kong
Ling-Qun
LQ
Lu
Lu
L
Wu
Wei-Zhong
WZ
Wang
Lu
L
Tang
Zhao-You
ZY
D000293:Adolescent; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000601:surgery; D018450:Disease Progression; D005260:Female; D006498:Hepatectomy; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D040081:Protein Array Analysis; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D016019:Survival Analysis; D055815:Young Adult
D016186:Receptor, Macrophage Colony-Stimulating Factor