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      The combination of strong expression of ZNF143 and high MIB-1 labelling index independently predicts shorter disease-specific survival in lung adenocarcinoma

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          Abstract

          Background:

          The transcription factor, zinc finger protein 143 (ZNF143), positively regulates many cell-cycle-related genes. The ZNF143 would show high expression of multiple solid tumours related closely to cancer cell growth, similar to the widely accepted Ki67 (MIB-1) protein, but the underlying mechanisms for ZNF143 remain unclear. We investigated the association of ZNF143 expression with clinicopathological features and prognoses of patients with lung adenocarcinoma.

          Methods:

          Expressions of ZNF143 and MIB-1 were immunohistochemically analysed in 183 paraffin-embedded tumour samples of patients with lung adenocarcinoma. The ZNF143 expression was considered to be strong when >30% of the cancer cells demonstrated positive staining.

          Results:

          Strong ZNF143+ expression showed a significantly close relationship to pathologically moderate to poor differentiation and highly invasive characteristics. The ZNF143 positivity potentially induced cell growth of lung adenocarcinoma, correlated significantly with high MIB-1 labelling index (⩾10%). Univariate and multivariate analyses demonstrated that both strong ZNF143+ and the high MIB-1 index group have only and significantly worse survival rates.

          Conclusions:

          The combination of strong ZNF143 expression and high MIB-1 index potentially predicts high proliferating activity and poor prognosis in patients with lung adenocarcinoma, and may offer a therapeutic target against ZNF143.

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          Most cited references 31

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          A Japanese Lung Cancer Registry study: prognosis of 13,010 resected lung cancers.

          The validation of tumor, node, metastasis staging system in terms of prognosis is an indispensable part of establishing a better staging system in lung cancer. In 2005, 387 Japanese institutions submitted information regarding the prognosis and clinicopathologic profiles of patients who underwent pulmonary resections for primary lung neoplasms in 1999 to the Japanese Joint Committee of Lung Cancer Registry. The data of 13,010 patients with only lung carcinoma histology (97.6%) were analyzed in terms of prognosis and clinicopathologic characteristics. The 5-year survival rate of the entire group was 61.4%. For the small cell histology (n = 390), the 5-year survival rates according to clinical (c) and pathologic (p) stages were as follows: 58.8% (n = 161) and 58.3% (n = 127) for IA, 58.0% (n = 77) and 60.2% (n = 79) for IB, 47.1% (n = 17) and 40.6% (n = 29) for IIA, 25.3% (n = 38) and 41.1% (n = 29) for IIB, 29.0% (n = 61) and 28.3% (n = 60) for IIIA, 36.3% (n = 19) and 34.6% (n = 40) for IIIB, and 27.8% (n = 12) and 30.8% for IV (n = 13). For the non-small cell histology (n = 12,620), the 5-year survival rates according to c-stage and p-stage were as follows: 77.3% (n = 5642) and 83.9% (n = 4772) for IA, 59.8% (n = 3081) and 66.3% (n = 2629) for IB, 54.1% (n = 205) and 61.0% (n = 361) for IIA, 43.9% (n = 1227) and 47.4% (n = 1330) for IIB, 38.3% (n = 1628) and 32.8% (n = 1862) for IIIA, 32.6% (n = 526) and 29.6% (n = 1108) for IIIB, and 26.5% (n = 198) and 23.1% (n = 375) for IV. Adenocarcinoma, female gender, and age less than 50 years were significant favorable prognostic factors. This large registry study provides benchmark prognostic statistics for lung cancer. The prognostic difference between stages IB and IIA was small despite different stages. Otherwise, the present tumor, node, metastasis staging system well characterizes the stage-specific prognoses.
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            One hundred years of lung cancer.

            A hundred years ago, lung cancer was a reportable disease, and it is now the commonest cause of death from cancer in both men and women in the developed world, and before long, will reach that level in the developing world as well. The disease has no particular symptoms or signs for its detection at an early stage. Most patients therefore present with advanced stage IIIB or IV disease. Screening tests began in the 1950s with annual chest x-ray films and sputum cytology but they resulted in no improvement in overall mortality compared with control subjects. The same question is now being asked of spiral low-dose computed tomographic scanning. There have been big refinements in the staging classification of lung cancer and advances in stage identification using minimally invasive technology. Postsurgical mortality has declined from the early days of the 1950s but 5-year cure rates have only barely improved. The addition of chemotherapy to radical radiotherapy, together with novel radiotherapy techniques, is gradually improving the outcome for locally advanced, inoperable non-small cell lung cancer. Chemotherapy offers modest survival improvement for patients with non-small cell lung cancer, the modern agents being better tolerated resulting in an improved quality of life. The management of small cell lung cancer, which appeared so promising at the beginning of the 1970s, has hit a plateau with very little advance in outcome over the last 15 years. The most important and cost-effective management for lung cancer is smoking cessation, but for those with the disease, novel agents and treatment approaches are urgently needed.
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              The IASLC Lung Cancer Staging Project: proposals regarding the relevance of TNM in the pathologic staging of small cell lung cancer in the forthcoming (seventh) edition of the TNM classification for lung cancer.

              For more than 50 years, small cell lung cancer (SCLC) has been staged mainly as either limited or extensive stage disease. Small published series of resected SCLC have suggested that the tumor, node, metastases (TNM) pathologic staging correlates with the survival of resected patients. Recent analysis of the 8088 cases of SCLC in the International Association for the Study of Lung Cancer (IASLC) database demonstrated the usefulness of clinical TNM staging in this malignancy. The IASLC data bank contains an unprecedented number of resected SCLC cases with pathologic staging information. This analysis was undertaken to examine the impact of the TNM system on the pathologic staging of SCLC and to assess the new IASLC proposals in this subtype of lung cancer. Using the IASLC database, survival analyses were performed for resected patients with SCLC. Prognostic groups were compared, and the new IASLC TNM proposals were applied to this population and to the Surveillance, Epidemiology, and End Results (SEER) database. The IASLC database contained 349 cases of resected SCLC where pathologic TNM staging was available. Survival after resection correlated with both T and N category with nodal status having a stronger influence on survival. Stage groupings using the 6th edition of TNM clearly identify patient subgroups with different prognoses. The IASLC proposals for the 7th edition of TNM classification also apply to this population and to the SEER database. This analysis further strengthens our previous recommendation to use TNM staging for all SCLC cases.
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                Author and article information

                Journal
                Br J Cancer
                Br. J. Cancer
                British Journal of Cancer
                Nature Publishing Group
                0007-0920
                1532-1827
                13 May 2014
                15 April 2014
                : 110
                : 10
                : 2583-2592
                Affiliations
                [1 ]Department of Health Policy and Management, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health , Kitakyushu 807-8555, Japan
                [2 ]Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health , Kitakyushu 807-8555, Japan
                [3 ]Department of Urology, School of Medicine, University of Occupational and Environmental Health , Kitakyushu 807-8555, Japan
                [4 ]Department of Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health , Kitakyushu 807-8555, Japan
                [5 ]Department of Medical Oncology, The First Hospital of China Medical University , Shenyang 110001, People's Republic of China
                [6 ]Laboratory of Pathology, Fukuoka Wajiro Hospital , Fukuoka 811-0213, Japan
                [7 ]Department of Occupational Pneumology, School of Medicine, University of Occupational and Environmental Health , Kitakyushu 807-8555, Japan
                [8 ]The President Laboratory, School of Medicine, University of Occupational and Environmental Health , Kitakyushu 807-8555, Japan
                Author notes
                [9]

                These authors contributed equally to this work.

                Article
                bjc2014202
                10.1038/bjc.2014.202
                4021533
                24736586
                5cf17325-2341-46b2-8404-2e82d37a3ab1
                Copyright © 2014 Cancer Research UK

                From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

                Categories
                Molecular Diagnostics

                Oncology & Radiotherapy

                lung adenocarcinoma, znf143, cell growth, mib-1, prognosis

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