Co-expression of SALL4 with HDAC1 and/or HDAC2 is associated with underexpression of PTEN and poor prognosis in patients with hepatocellular carcinoma

Publication date: Available online 12 April 2017
Source:Human Pathology
Author(s): Huanlin Wang, Kenichi Kohashi, Tomoharu Yoshizumi, Yukihiko Okumura, Yuki Tanaka, Masahiro Shimokawa, Takeshi Iwasaki, Shinichi Aishima, Yoshihiko Maehara, Yoshinao Oda
Spalt-like transcriptional factor 4 (SALL4), a stem marker, is re-activated in several cancers. A previous study has demonstrated that SALL4 interacts with the nucleosome remodeling deacetylase complex (NuRD), which contains histone deacetylase 1 (HDAC1) and histone deacetylase 2 (HDAC2). In this study we investigated the expression status of SALL4, HDAC1 and HDAC2 and their relationship with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) by immunohistochemical analysis of the post-hepatectomy specimens of 135 patients with hepatocellular carcinoma (HCC) who were treated at our hospital. Ninety-two frozen samples were subjected to quantitative reverse transcription polymerase chain reaction analysis to detect the mRNA levels of PTEN. Seventy-six of 135 patients (56%) were positive for SALL4, and this group had a higher prevalence of HBs antigen, a higher value of AFP and PIVKAII and poor histological differentiation. The five-year survival rate was significantly lower in the SALL4-positive group. High HDAC1 expression (51%) was correlated with a poor histological differentiation and a poor prognosis. High HDAC2 expression (46%) was associated with a higher prevalence of HBs antigen positivity, a poor histological differentiation and higher prevalence of vascular invasion, and a lower 5-year-survival rate. Co-expression of SALL4 with HDAC1 and/or HDAC2 was correlated with underexpression of PTEN. Moreover, multivariable analysis revealed that co-expression of SALL4 with HDAC1 and/or HDAC2 was predictive of an unfavorable prognosis. Our data thus suggested that the combination of SALL4, HDAC1 and HDAC2 may provide a potential target for molecular therapy.



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