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      Responses to crizotinib and disease monitoring with circulating tumor cells in lung adenocarcinoma patient with MET exon 14 skipping mutation : A case report

      case-report

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          Abstract

          Rationale:

          Mesenchymal-to-epithelial transition (MET) exon 14 skipping mutation was a targetable alteration in nonsmall-cell lung cancer (NSCLC), and the MET inhibitor of crizotinib had the most efficacy among all the targeted drugs. Most of the cancer-related deaths are associated with metastasis. Circulating tumor cells (CTCs) have been a valuable biomarker in assessing metastasis. Recent experiences suggested that CTCs detection may help improve diagnosis and predict prognosis for patients with NSCLC. However, few literatures have reported the CTCs detection based on the (MET) exon 14 skipping, which are positive in NSCLC patients.

          Patient concerns:

          The patient, a 69-year-old Chinese male, with a 50 years history of smoking. Because of the cough, the patient went to the hospital and found the upper right lung tumor and the right supraclavicular lymph node enlarged. He was worried that it was cancer.

          Diagnoses:

          The patient was performed biopsy of the right clavicle lymph node metastasis on October 12 and sent the tissue specimen for pathological evaluation. Finally, the patient was diagnosed to be with a pT3N3Mx stage IIIC lung adenocarcinoma.

          Interventions:

          The patient began to take orally crizotinib 250 mg twice a day for the medical therapy after lymph node biopsy. At the same time, the CTCs were detected to observe the prognosis of the patients.

          Outcomes:

          Compared with the first CTCs result, the second test revealed a decrease in the amount of CTCs, while the mesenchymal CTCs have increased, indicating the possibility of distal metastasis.

          Lessons:

          This is the first proof that CTCs can be quantitatively assayed by MET exon 14 skipping mutation, which demonstrates the clinical response to crizotinib. More cases should be reported and further evaluation for treatment options and prognosis evaluation is necessary.

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          Most cited references16

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          High frequency of PIK3R1 and PIK3R2 mutations in endometrial cancer elucidates a novel mechanism for regulation of PTEN protein stability.

          We demonstrate that phosphatidylinositol 3-kinase (PI3K) pathway aberrations occur in >80% of endometrioid endometrial cancers, with coordinate mutations of multiple PI3K pathway members being more common than predicted by chance. PIK3R1 (p85α) mutations occur at a higher rate in endometrial cancer than in any other tumor lineage, and PIK3R2 (p85β), not previously demonstrated to be a cancer gene, is also frequently mutated. The dominant activation event in the PI3K pathway appears to be PTEN protein loss. However, in tumors with retained PTEN protein, PI3K pathway mutations phenocopy PTEN loss, resulting in pathway activation. KRAS mutations are common in endometrioid tumors activating independent events from PI3K pathway aberrations. Multiple PIK3R1 and PIK3R2 mutations demonstrate gain of function, including disruption of a novel mechanism of pathway regulation wherein p85α dimers bind and stabilize PTEN. Taken together, the PI3K pathway represents a critical driver of endometrial cancer pathogenesis and a novel therapeutic target.
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            CSF concentration of the anaplastic lymphoma kinase inhibitor crizotinib.

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              Circulating tumor cells as a window on metastasis biology in lung cancer.

              Circulating tumor cell (CTC) number in metastatic cancer patients yields prognostic information consistent with enhanced cell migration and invasion via loss of adhesion, a feature of epithelial-to-mesenchymal transition (EMT). Tumor cells also invade via collective migration with maintained cell-cell contacts and consistent with this is the circulating tumor microemboli (CTM; contiguous groups of tumor cells) that are observed in metastatic cancer patients. Using a blood filtration approach, we examined markers of EMT (cytokeratins, E-cadherin, vimentin, neural cadherin) and prevalence of apoptosis in CTCs and CTM to explore likely mechanism(s) of invasion in lung cancer patients and address the hypothesis that cells within CTM have a survival advantage. Intra-patient and inter-patient heterogeneity was observed for EMT markers in CTCs and CTM. Vimentin was only expressed in some CTCs, but in the majority of cells within CTM; E-cadherin expression was lost, cytoplasmic or nuclear, and rarely expressed at the surface of the cells within CTM. A subpopulation of CTCs was apoptotic, but apoptosis was absent within CTM. This pilot study suggests that EMT is not prosecuted homogeneously in tumor cells within the circulation of lung cancer patients and that collective migration and enhanced survival of cells within CTM might contribute to lung cancer metastasis. Multiplex analysis and further detailed exploration of metastatic potential and EMT in CTCs/CTM is now warranted in a larger patient cohort. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                November 2017
                27 November 2017
                : 96
                : 47
                : e8744
                Affiliations
                Department of Cardiothoracic Surgery, First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China.
                Author notes
                []Correspondence: Mingwu Chen, Department of Cardiothoracic Surgery, First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, 0771, China (e-mail: chen535@ 123456126.com ).
                Article
                MD-D-17-03629 08744
                10.1097/MD.0000000000008744
                5708966
                29381967
                f468d4d6-7cc3-41a9-8c81-a4132883d30d
                Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the Creative Commons Attribution-NoDerivatives License 4.0, which allows for redistribution, commercial and non-commercial, as long as it is passed along unchanged and in whole, with credit to the author. http://creativecommons.org/licenses/by-nd/4.0

                History
                : 11 June 2017
                : 24 October 2017
                : 26 October 2017
                Categories
                5700
                Research Article
                Clinical Case Report
                Custom metadata
                TRUE

                exon 14 skipping,crizotinib,circulating tumor cells (ctcs),lung adenocarcinoma,met

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