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      Stromal IL2 is related to the neutrophil/lymphocyte ratio in epithelial ovarian cancer

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          Summary

          Introduction

          There is a need for the development of new biomarkers for diagnosis and prognosis of ovarian cancer, which can ideally serve as targets for new therapeutic modalities and individualization of treatment. The objectives of this study were to determine the prognostic significance of the neutrophil/lymphocyte ratio in the peripheral blood of patients with ovarian cancer and tumor staging, and to associate this marker with the immune expression of a panel of cytokines.

          Methods

          The study included 24 patients with malignant ovarian neoplasia treated at the Pelvic Mass Outpatient Clinic of the Clinical Hospital of the Federal University of Triângulo Mineiro. The neutrophil/lymphocyte ratio was calculated as the absolute number of neutrophils divided by the absolute number of lymphocytes. Expression of the cytokines was evaluated by the immunohistochemistry method (IL2, IL5, IL6, IL8, IL10 and TNF-R1). Fisher’s statistical test was used for the comparisons of immunohistochemical expression with the neutrophil/lymphocyte ratio, and the unpaired T-Test was used in the analysis of the association of this ratio with tumor staging.

          Results

          A neutrophil/lymphocyte ratio > 2.6 was significantly higher in the more advanced stages (II-IV) of malignant ovarian neoplasia (p = 0.0098). In addition, this ratio > 2.6 was associated with IL2 stromal immunostaining (1-3) (p = 0.0472).

          Conclusion

          Stromal IL-2 is associated with higher a neutrophil/lymphocyte ratio, suggesting a worse prognosis in ovarian cancer and its role in tumor immunology; a neutrophil/lymphocyte ratio > 2.6 is associated with more advanced stages of malignant ovarian neoplasia.

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          Most cited references26

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          Cancer Statistics, 2017.

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics. In 2017, 1,688,780 new cancer cases and 600,920 cancer deaths are projected to occur in the United States. For all sites combined, the cancer incidence rate is 20% higher in men than in women, while the cancer death rate is 40% higher. However, sex disparities vary by cancer type. For example, thyroid cancer incidence rates are 3-fold higher in women than in men (21 vs 7 per 100,000 population), despite equivalent death rates (0.5 per 100,000 population), largely reflecting sex differences in the "epidemic of diagnosis." Over the past decade of available data, the overall cancer incidence rate (2004-2013) was stable in women and declined by approximately 2% annually in men, while the cancer death rate (2005-2014) declined by about 1.5% annually in both men and women. From 1991 to 2014, the overall cancer death rate dropped 25%, translating to approximately 2,143,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the cancer death rate was 15% higher in blacks than in whites in 2014, increasing access to care as a result of the Patient Protection and Affordable Care Act may expedite the narrowing racial gap; from 2010 to 2015, the proportion of blacks who were uninsured halved, from 21% to 11%, as it did for Hispanics (31% to 16%). Gains in coverage for traditionally underserved Americans will facilitate the broader application of existing cancer control knowledge across every segment of the population. CA Cancer J Clin 2017;67:7-30. © 2017 American Cancer Society.
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            Cancer-related inflammation.

            The mediators and cellular effectors of inflammation are important constituents of the local environment of tumours. In some types of cancer, inflammatory conditions are present before a malignant change occurs. Conversely, in other types of cancer, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumours. Regardless of its origin, 'smouldering' inflammation in the tumour microenvironment has many tumour-promoting effects. It aids in the proliferation and survival of malignant cells, promotes angiogenesis and metastasis, subverts adaptive immune responses, and alters responses to hormones and chemotherapeutic agents. The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.
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              Inflammation and cancer: back to Virchow?

              The response of the body to a cancer is not a unique mechanism but has many parallels with inflammation and wound healing. This article reviews the links between cancer and inflammation and discusses the implications of these links for cancer prevention and treatment. We suggest that the inflammatory cells and cytokines found in tumours are more likely to contribute to tumour growth, progression, and immunosuppression than they are to mount an effective host antitumour response. Moreover cancer susceptibility and severity may be associated with functional polymorphisms of inflammatory cytokine genes, and deletion or inhibition of inflammatory cytokines inhibits development of experimental cancer. If genetic damage is the "match that lights the fire" of cancer, some types of inflammation may provide the "fuel that feeds the flames". Over the past ten years information about the cytokine and chemokine network has led to development of a range of cytokine/chemokine antagonists targeted at inflammatory and allergic diseases. The first of these to enter the clinic, tumour necrosis factor antagonists, have shown encouraging efficacy. In this article we have provided a rationale for the use of cytokine and chemokine blockade, and further investigation of non-steroidal anti-inflammatory drugs, in the chemoprevention and treatment of malignant diseases.
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                Author and article information

                Journal
                Pathologica
                Pathologica
                PATHOL
                Pathologica
                Pacini Editore srl
                0031-2983
                1591-951X
                01 June 2019
                June 2019
                : 111
                : 2
                : 62-66
                Affiliations
                [1 ] Research Institute of Oncology (IPON)/Discipline of Gynecology and Obstetrics , Uberaba, MG, Brazil
                [2 ] Discipline of Special Pathology; Federal University of Triângulo Mineiro , Uberaba, MG, Brazil
                Author notes
                Correspondence: Rosekeila Simões Nomelini, Research Institute of Oncology (IPON)/Discipline of Gynecology and Obstetrics, UFTM, Av. Getúlio Guaritá, s/n, Bairro Abadia, 38025-440 Uberaba-MG, Brazil - E-mail: rosekeila@ 123456terra.com.br ; rosekeila.nomelini@ 123456pq.cnpq.br
                Article
                10.32074/1591-951X-62-18
                8186009
                31388197
                118e598e-9019-4569-bf0b-a379b0972d91
                © 2019 Copyright by Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) , which permits for noncommercial use, distribution, and reproduction in any digital medium, provided the original work is properly cited and is not altered in any way. For details, please refer to https://creativecommons.org/licenses/by-nc-nd/4.0/

                History
                : 13 September 2018
                : 16 June 2019
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 27, Pages: 5
                Categories
                Original Article

                neutrophil/lymphocyte ratio,staging,il-2,immunohistochemistry,ovarian cancer

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