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      Tumour-stroma ratio and prognosis in gastric adenocarcinoma

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          Abstract

          Background

          Tumour microenvironment, including tumour–stroma ratio (TSR), might help identifying high-risk cancer patients. However, the significance of TSR in gastric cancer is unclear, especially in the intestinal and diffuse subtypes. The aim of this study was to investigate the tumour–stroma ratio in gastric adenocarcinoma, and its intestinal and diffuse histological subtypes, in relation to prognosis.

          Methods

          Five hundred and eighty-three gastric adenocarcinoma patients who underwent surgery in Oulu University hospital during years 1983–2016 were included in this retrospective cohort study. TSR was analysed from the slides that were originally used for diagnostic purposes. Patients were divided into stroma-poor (≤50% stroma) and stroma-rich (>50% stroma) groups and TSR was analysed in relation to 5-year mortality and overall mortality.

          Results

          Patients with stroma-rich tumours had worse 5-year prognosis (HR 1.80, 95% CI 1.41–2.28) compared to stroma-poor tumours. Stratified analysis showed that stroma-rich tumours had worse 5-year prognosis in both intestinal (HR 1.68, 95% CI 1.24–2.27) and diffuse histological types (HR 2.09, 95% CI 1.35–3.23) compared to stroma-poor tumours, respectively.

          Conclusions

          High proportion of stroma is an independent prognostic factor in both intestinal and diffuse histological subtypes of gastric adenocarcinoma.

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          Most cited references12

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          Epidemiology of gastric cancer

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            Exclusion of Kaposi Sarcoma From Analysis of Cancer Burden—Reply

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              The carcinoma-associated fibroblast expressing fibroblast activation protein and escape from immune surveillance.

              The fibroblastic element of the tumor microenvironment has been of great interest to cancer biologists but less so to cancer immunologists. Yet, the sharing of a common mesenchymal cell type in the stroma of tumors and at sites of chronic inflammatory lesions, some of which have an autoimmune basis, has been a strong hint that this cellular component of the tumor microenvironment may have an immunologic function. Recent studies have confirmed this possibility. These fibroblast-like cells, which are termed carcinoma-associated fibroblasts (CAF), can be identified by their expression of the membrane protein, fibroblast activation protein-α (FAP). The conditional depletion of the FAP(+) CAF permits immune control not only of an artificial, transplanted tumor, but also of an autochthonous model of pancreatic ductal adenocarcinoma (PDA) that replicates the molecular, histologic, clinical, and immunologic characteristics of the human disease. Immune suppression by the FAP(+) CAF is mediated by CXCL12, the chemokine that binds to cancer cells and excludes T cells by a mechanism that depends on signaling by the CXCL12 receptor CXCR4. Inhibition of CXCR4 leads to the elimination of cancer cells by enabling the rapid, intratumoral accumulation of preexisting, PDA-specific CD8(+) T cells, and reveals the antitumor efficacy of the T-cell checkpoint antagonist anti-PD-L1. Recent studies have also shown that the FAP(+) CAF is related to FAP-expressing stromal cells of normal tissues, demonstrating that cancers recruit a member of an essential stromal cell lineage that is involved not only in wound repair but also in normal tissue homeostasis. These findings extend the concept introduced by cancer biologists that the fibroblastic component of tumors has a critical role in the adaptation of the cancer to the host. ©2014 AACR.
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                Author and article information

                Contributors
                niko.kemi@oulu.fi
                Journal
                Br J Cancer
                Br. J. Cancer
                British Journal of Cancer
                Nature Publishing Group UK (London )
                0007-0920
                1532-1827
                30 July 2018
                14 August 2018
                : 119
                : 4
                : 435-439
                Affiliations
                [1 ]ISNI 0000 0001 0941 4873, GRID grid.10858.34, Cancer and Translational Medicine Research Unit, Medical Research Center, , University of Oulu and Oulu University Hospital, ; Oulu, Finland
                [2 ]ISNI 0000 0000 9241 5705, GRID grid.24381.3c, Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, , Karolinska University Hospital, ; Stockholm, Sweden
                Author information
                http://orcid.org/0000-0001-6012-0010
                Article
                202
                10.1038/s41416-018-0202-y
                6133938
                30057407
                697bc48a-dc4e-4b52-ad88-80a54351c548
                © Cancer Research UK 2018

                Note: This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

                History
                : 12 May 2018
                : 4 July 2018
                : 6 July 2018
                Funding
                Funded by: Thelma Mäkikyrö foundation
                Funded by: Sigrid Jusélius Foundation, Orion Research Foundation, Thelma Mäkikyrö Foundation and Mary and Georg C. Ehrnroot Foundation
                Categories
                Article
                Custom metadata
                © Cancer Research UK 2018

                Oncology & Radiotherapy
                cancer microenvironment,gastric cancer
                Oncology & Radiotherapy
                cancer microenvironment, gastric cancer

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