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- W2086941898 abstract "Introduction: Lung neuroendocrine tumors (NET) comprise typical (TC) and atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC). Phosphatase and tensin homolog (PTEN) protein is a known cytosolic tumor suppressor with recently described novel nuclear functions. We investigated this differential PTEN protein compartmentalization together with its genomic status in pulmonary NETs. Patients and Methods: A retrospective multicenter cohort of 192 patients with lung NET was investigated on a tissue microarray (TMA, surgical resections = 183/autopsies = 9) by immunohistochemistry (IHC, cytoplasm and nucleus) and fluorescence in-situ hybridization (FISH, nucleus). Results were correlated with markers of neuroendocrine differentiation (synaptophysin, chromogranin A), proliferation (mib-1), cell cycle (p27, cyclin D1) and survival data. Results: The histotypes represented were TC in 58 patients, AC in 42, LCNEC in 32 and SCLC in 60. All NETs showed higher PTEN immunoreactivity in the cytoplasm than in the nucleus, whereby the greatest nucleo-cytoplasmic difference was found for SCLC. In both compartments, immunoreactivity was higher in the carcinoids than in LCNEC and SCLC. Loss of cytosolic or nuclear PTEN protein was correlated with increased mitotic rate, with low synaptophysin or chromogranin A and with PTEN genomic deletion. Loss of nuclear PTEN protein correlated with high nuclear TTF1, whereas loss of cytosolic protein correlated with low p27 and low cyclin D1 (all p-values <0.05). Patients with PTEN genomic deletion or low PTEN immunoreactivity had poorer survivals. Conclusion: PTEN genomic deletion or PTEN protein loss is linked to dedifferentiation and poor prognosis of lung NET. Nucleo-cytoplasmic shuttling of PTEN protein could play a role in the different PTEN inactivation mechanisms.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4159. doi:1538-7445.AM2012-4159" @default.
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- W2086941898 date "2012-04-15" @default.
- W2086941898 modified "2023-09-25" @default.
- W2086941898 title "Abstract 4159: PTEN nucleo-cytoplasmic protein compartmentalization and gene status are correlated with aggressiveness of pulmonary neuroendocrine tumors" @default.
- W2086941898 doi "https://doi.org/10.1158/1538-7445.am2012-4159" @default.
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