ORIGINAL ARTICLE

Altered p-STAT3 (tyr705) expression is associated with histological grading and intratumour microvessel density in hepatocellular carcinoma

Sheau-Fang Yang^1,*, Shen-Nien Wang^2,3,*, Chih-Fung Wu⁴, Yao-Tsung Yeh³, Chee-Yin Chai¹, Shih-Chang Chunag², Maw-Chang Sheen⁴, King-Teh Lee²

¹ Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
² Division of Hepatobiliary Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
³ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
⁴ Division of Surgical Oncology, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Correspondence to:
Dr King-Teh Lee
Chairman and Professor, Department of Surgery, Kaohsiung Medical University Chung-Ho Memorial Hospital, No 100, Tzyou 1st Road, Kaohsiung 807, Taiwan; ktlee{at}cc.kmu.edu.tw

Background: Constitutive activation of signal transducer and activator of transcription 3 at tyrosine residue 705 (p-STAT3 (tyr705)) has been associated with many types of human cancers. However, its potential roles and biological effects in hepatocellular carcinoma (HCC) are not well established.

Aim: To explore whether an altered p-STAT3 (tyr705) expression is associated with angiogenesis or proliferation and thereby plays a part in HCC development.

Methods: Paraffin-wax-embedded sections from 69 patients with HCC were collected in this study. Using a semiquantitative immunohistochemical staining method, the expression patterns of p-STAT3 (tyr705) in both HCC lesions and the adjacent non-tumorous liver parenchyma were analysed. The results obtained were further correlated with intratumour microvessel density (MVD), Ki-67 expression, clinicopathological parameters and overall survival.

Results: A strong p-STAT3 (tyr705) nuclear staining was observed in 49.3% of HCC lesions, but was reported only in 5.8% of the adjacent non-tumorous liver parenchyma (p<0.001). The expression of p-STAT3 (tyr705) in HCC lesions was significantly and positively correlated with the intratumour MVD (p = 0.002), but not with Ki-67 expression. No significant correlation of p-STAT3 (tyr705) was found in addition to histological grading (p = 0.019). Multivariate Cox regression analysis showed that p-STAT3 (tyr705) expression was a significant predictor of overall survival for HCC (p = 0.036), although the Kaplan–Meier survival curves showed no significant difference between the high and low p-STAT3 (tyr705) expression subgroups.

Conclusions: The results showed that p-STAT3 (tyr705) expression was closely correlated with histological grading and intratumour MVD in HCC. Thus, the potential role of p-STAT3 (tyr705) in HCC development may be through these correlations.

Abbreviations: HBV, hepatitis B virus; HCV, hepatitis C virus; HCC, hepatocellular carcinoma; MVD, microvessel density; p-STAT3 (tyr705), phosphorylated signal transducer and activator of transcription protein 3 at tyrosine residue 705; VEGF, vascular endothelial growth factor

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