Published in:
01-02-2012 | Hepatobiliary Tumors
Infiltrating Memory/Senescent T Cell Ratio Predicts Extrahepatic Metastasis of Hepatocellular Carcinoma
Authors:
Qiang Gao, MD, PhD, Jian Zhou, MD, PhD, Xiao-Ying Wang, MD, PhD, Shuang-Jian Qiu, MD, PhD, Kang Song, MD, PhD, Xiao-Wu Huang, MD, PhD, Jian Sun, MD, PhD, Ying-Hong Shi, MD, PhD, Bai-Zhou Li, MD, PhD, Yong-Sheng Xiao, MD, PhD, Jia Fan, MD, PhD
Published in:
Annals of Surgical Oncology
|
Issue 2/2012
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Abstract
Background
The density of tumor-infiltrating immunocytes (TICs) has been proposed as an independent predictor of intrahepatic recurrence in patients with hepatocellular carcinoma (HCC). However, the relative roles of TIC density in predicting tumor extrahepatic metastasis remain to be elucidated.
Methods
The densities of CD3+, CD8+, granzyme B+, FoxP3+, CD45RO+, CD20+, CD1a+, CD83+, CD57+, and CD68+ TICs were assessed by immunohistochemistry in tissue microarrays containing paired intratumoral (IT) and peritumoral (PT) tissues from 206 consecutive HCC patients who underwent liver transplantation. Occurrence of extrahepatic metastasis, recurrence-free survival (RFS), and cancer-specific survival (CSS) were assessed retrospectively in relation to TIC densities.
Results
CD45RO+ memory T cell density was lower in tumor tissue compared with peritumor, whereas CD57+ senescent T cell density was higher. Univariate analysis revealed that increased CD45RO
IT
+
and decreased CD57
PT
+
densities were statistically significantly associated with favorable RFS and CSS, while other types of TICs, intratumorally or peritumorally, showed no prognostic values. Further, the CD45RO
IT
+
/CD57
PT
+
ratio could stratify patients more accurately in terms of RFS and CSS than either marker used alone. Finally, multivariate analysis indicated that a high CD45RO
IT
+
/CD57
PT
+
ratio was independently associated with better RFS (hazard ratio [HR] = 0.64; 95% confidence interval [CI], 0.42 to 0.98; P = 0.040) and CSS (HR = 0.51; 95% CI, 0.31 to 0.83; P = 0.007), but not CD45RO
IT
+
or CD57
PT
+
individually.
Conclusions
These results suggest that the CD45RO
IT
+
/CD57
PT
+
(memory/senescent T cell) ratio is of vital importance in preventing HCC extrahepatic metastasis and in particular demonstrates its independent prognostic value in liver transplant recipients.