Combination of peritumoral mast cells and T-regulatory cells predicts prognosis of hepatocellular carcinoma.
The peritumoral inflammatory environment is critical for the progression of intrahepatic recurrence of hepatocellular carcinoma (HCC) after curative resections. Here, we investigated the relevance of peritumoral mast cells (MCs) to HCC outcomes. Peritumoral tryptase(+) MCs in addition to Foxp3(+) T-regulatory cells (Tregs) were evaluated using immunohistochemistry enumeration in tissue microarrays containing 207 randomly selected HCC patients. Clinicopathological factors and postoperative outcomes were compared between high and low subgroups of MCs or Tregs. Compared to low denstiy, higher peritumoral MCs were associated with poorer clinical outcomes, and independently related to elevated 5-year recurrence incidence (54.1%vs 39.2%, P = 0.026). High-dense MCs were especially related to increased probability of early recurrence (within 2 years) (P = 0.004). We also found that peritumoral Tregs were positively correlated with MCs in density (r = 0.353, P < 0.001) and reversely related to HCC outcomes. Notably, MCs in combination with Tregs displayed better prognostic performances than MCs alone (area under curve [AUC](survival) = 0.629 vs 0.589, AUC(recurrence) = 0.632 vs 0.591). Moreover, MCs were positively correlated to alanine aminotransferase, a serum inflammatory marker (P = 0.014). Therefore, peritumoral MCs are promising prognostic parameters for HCC mainly through inflammation response-related mechanisms, and we propose that MCs and Tregs may cooperate with each other and result in poorer prognosis.
Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School of Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, Chinese Ministry of Education, Shanghai, China.
Min-Jie
MJ
Ju
Shuang-Jian
SJ
Qiu
Qiang
Q
Gao
Jia
J
Fan
Ming-Yan
MY
Cai
Yi-Wei
YW
Li
Zhao-You
ZY
Tang
D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000473:pathology*; D008297:Male; D008407:Mast Cells / Q000473:pathology*; D008875:Middle Aged; D011379:Prognosis; D050378:T-Lymphocytes, Regulatory / Q000473:pathology*