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BACKGROUND Inactivation of the tumor suppressor gene PTEN/MMAC1/TEP1, located on chromosome 10q23, is a common event in advanced stages of diverse human malignancies. However, the prognostic role of PTEN expression in patients with hepatocellular carcinoma (HCC) has not been characterized. METHODS One hundred five resected specimens were collected from patients with HCC. Expression levels of PTEN and p53 in clinical samples were analyzed by immunohistochemistry. RESULTS Immunohistochemical analysis of 105 HCC tissue specimens revealed that decreased or absence of PTEN immunostaining was found in 43 specimens (40.9%). Reduced PTEN expression levels were correlated with increased tumor grade (P = 0.017), advanced disease stage (P = 0.016), and elevated serum α‐fetoprotein (αFP) levels (P = 0.001). Kaplan–Meier analysis indicated that patients with reduced PTEN levels had shorter overall survival (P = 0.001) and higher recurrence rates (P = 0.0007) compared with patients who had intact PTEN expression. Examining p53 expression unveiled an inverse correlation between p53 overexpression and reduced PTEN expression in patients with HCC (P = 0.004). In addition, patients with p53 overexpression had shorter overall survival compared with patients who were without p53 overexpression (P = 0.0014). Univariate and multivariate analyses revealed that reduced PTEN expression was an independent prognostic factor for survival in patients with HCC. CONCLUSIONS The current study demonstrated that reduced PTEN expression levels are involved in the pathogenesis of HCC. Moreover, decreased PTEN expression was correlated with tumor progression, high αFP levels, p53 overexpression, and poor prognosis in patients with HCC. Cancer 2003;97:1929–40. © 2003 American Cancer Society. DOI 10.1002/cncr.11266

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Hepatoma-derived growth factor (HDGF) participates in tumourigenesis but its role in breast cancer is unclear. We set out to elucidate the expression profile and function of HDGF during breast carcinogenesis. Immunoblot and immunohistochemical studies revealed elevated HDGF expression in human breast cancer cell lines and tissues. Nuclear HDGF labelling index was positively correlated with tumour grade, stage and proliferation index, but negatively correlated with survival rate in breast cancer patients. HDGF over-expression was associated with lymph node metastasis and represented an independent prognostic factor for tumour recurrence. Gene transfer studies were performed to elucidate the influence of cellular HDGF level on the malignant behaviour and epithelial-mesenchymal transition (EMT) of breast cancer cells. Adenovirus-mediated HDGF over-expression stimulated the invasiveness and colony formation of MCF-7 cells. Moreover, HDGF over-expression promoted breast cancer cell EMT by E-cadherin down-regulation and vimentin up-regulation. Conversely, HDGF knockdown by RNA interference in MDA-MB-231 cells attenuated the malignant behaviour and elicited EMT reversal by enhancing E-cadherin expression while depleting vimentin expression. Because HDGF is a secreted protein, we evaluated the cellular function of recombinant HDGF and found that exogenously supplied HDGF enhanced the invasiveness of breast cancer cells by down-regulating E-cadherin and up-regulating vimentin at transcriptional and translational levels. In contrast, blockade of HDGF secretion with an HDGF antibody inhibited the malignant behaviours and EMT. Finally, exogenous HDGF partially reversed benzyl isothiocyanate (BITC)-induced EMT suppression. HDGF over-expression may exert a prognostic role for tumour metastasis and recurrence in breast cancer by modulating EMT. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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