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High Expression of Macrophage Colony-Stimulating Factor in Peritumoral Liver Tissue Is Associated With Poor Survival After Curative Resection of Hepatocellular Carcinoma

Xiao-Dong Zhu, Ju-Bo Zhang, Peng-Yuan Zhuang, Hong-Guang Zhu, Wei Zhang, Yu-Quan Xiong, Wei-Zhong Wu, Lu Wang, Zhao-You Tang, Hui-Chuan Sun

From the Liver Cancer Institute and Zhongshan Hospital, and Department of Pathology and Pathology Research Center, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China

Corresponding author: Hui-Chuan Sun, MD, PhD, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai 200032, China; e-mail: sun.huichuan{at}zs-hospital.sh.cn

Purpose: To investigate prognostic values of the intratumoral and peritumoral expression of macrophage colony-stimulating factors (M-CSF) in hepatocellular carcinoma (HCC) patients after curative resection.

Patients and Methods: Expression of M-CSF and density of macrophages (M) were assessed by immunohistochemistry in tissue microarrays containing paired tumor and peritumoral liver tissue from 105 patients who had undergone hepatectomy for histologically proven HCC. Prognostic value of these and other clinicopathologic factors was evaluated.

Results: Neither intratumoral M-CSF nor M density was associated with overall survival (OS) or disease-free survival (DFS). High peritumoral M-CSF and M density, which correlated with large tumor size, presence of intrahepatic metastasis, and high TNM stage, were independent prognostic factors for both OS (P = .001 and P < .001, respectively) and DFS (P = .001 and P = .003, respectively) and affected incidence of early recurrence. In a small HCC subset, peritumoral M-CSF was also correlated with both OS and DFS (P = .038 and P = .001, respectively). The combination of peritumoral M-CSF and M had a better power to predict the patients' death and disease recurrence (P < .001 for both).

Conclusion: High peritumoral M-CSF and M were associated with HCC progression, disease recurrence, and poor survival after hepatectomy, highlighting the importance of peritumoral tissue in the recurrence and metastasis of HCC. M-CSF and M may be targets of postoperative adjuvant therapy.

Supported by Grants No. 30672037 and 30300400 from the National Natural Science Foundation of China and the Foundation of China National "211" Project for Higher Education.

Both X.-D.Z. and J.-B.Z. contributed equally to this work.

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.