Ryo Nosaka1, Fumiyuki Yamasaki2, Taiichi Saito2, Takeshi Takayasu2, Manish Kolakshyapati2, Vishwa Jeet Amatya3, Yukio Takeshima3, Kazuhiko Sugiyama4, Kaoru Kurisu2. 1. Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. Electronic address: d113208@hiroshima-u.ac.jp. 2. Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. 3. Department of Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan. 4. Department of Clinical Oncology & Neuro-oncology Program, Hiroshima University Hospital, Hiroshima 734-8551, Japan.
Abstract
BACKGROUND: Earlier studies proposed phosphatase and tensin homolog (PTEN) acts as a 3'-specific phosphatidylinositol phosphatase and inhibits the PI3K pathway. Recent reports show that PTEN mRNA expression is significantly downregulated in brain metastases compared to primary breast cancer. We focused on the differential expression of nuclear and cytoplasmic PTEN between primary tumors and brain metastases. MATERIALS AND METHODS: We retrospectively studied 30 patients with histologically confirmed primary tumors and brain metastases. PTEN and PDK1 expression levels were examined by immunohistochemical staining and categorized as negative, positive, or strong positive expression. The difference in PTEN expression levels were compared, and the values with P<0.05 were considered statistically significant. RESULTS: Expression of cytoplasmic PTEN was 100% at primary site, and 70% at brain metastases. Expression of nuclear PTEN was 87% at primary site, and 20% at brain metastases. Study results demonstrated that PTEN expression levels in brain metastases are lower compared with that of primary tumors. Especially, nuclear PTEN expression was significantly downregulated in various brain metastases. Higher PDK1 expression at brain metastases also confirmed the down regulation of PTEN function. CONCLUSIONS: Our findings indicate that decreased PTEN function by loss of nuclear PTEN expression may be associated with brain metastases.
BACKGROUND: Earlier studies proposed phosphatase and tensin homolog (PTEN) acts as a 3'-specific phosphatidylinositol phosphatase and inhibits the PI3K pathway. Recent reports show that PTEN mRNA expression is significantly downregulated in brain metastases compared to primary breast cancer. We focused on the differential expression of nuclear and cytoplasmic PTEN between primary tumors and brain metastases. MATERIALS AND METHODS: We retrospectively studied 30 patients with histologically confirmed primary tumors and brain metastases. PTEN and PDK1 expression levels were examined by immunohistochemical staining and categorized as negative, positive, or strong positive expression. The difference in PTEN expression levels were compared, and the values with P<0.05 were considered statistically significant. RESULTS: Expression of cytoplasmic PTEN was 100% at primary site, and 70% at brain metastases. Expression of nuclear PTEN was 87% at primary site, and 20% at brain metastases. Study results demonstrated that PTEN expression levels in brain metastases are lower compared with that of primary tumors. Especially, nuclear PTEN expression was significantly downregulated in various brain metastases. Higher PDK1 expression at brain metastases also confirmed the down regulation of PTEN function. CONCLUSIONS: Our findings indicate that decreased PTEN function by loss of nuclear PTEN expression may be associated with brain metastases.
Authors: Zahra Rattray; Gang Deng; Shenqi Zhang; Anupama Shirali; Christopher K May; Xiaoyong Chen; Benedette J Cuffari; Jun Liu; Pan Zou; Nicholas Jw Rattray; Caroline H Johnson; Valentina Dubljevic; James A Campbell; Anita Huttner; Joachim M Baehring; Jiangbing Zhou; James E Hansen Journal: JCI Insight Date: 2021-07-22