{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T04:05:46Z","timestamp":1779768346168,"version":"3.53.1"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2021\/13861\u20100"],"award-info":[{"award-number":["2021\/13861\u20100"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["APMIS"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Tumor budding (TB) and poorly differentiated clusters (PDCs) are histopathological indicators of invasive potential in colorectal cancer (CRC). Concurrently,\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Fusobacterium nucleatum<\/jats:italic>\n                    <\/jats:styled-content>\n                    (\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    ) has emerged as a modulator of CRC progression. The relationship between intratumoral\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    and aggressive tumor architecture remains unknown. We evaluated 257 stage II primary CRCs. TB and PDC were assessed at the invasive front. Intratumoral\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    DNA was quantified from FFPE samples using droplet digital PCR. Associations between\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    load and molecular and clinicopathological features were analyzed.\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    was detected in 44.4% of tumors, with 19.8% classified as high bacterial load. Tumors with high\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    had a significantly higher frequency of intermediate\u2010 and high\u2010grade PDCs (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.047), with a specific enrichment for high\u2010grade PDCs (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.019). High\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    load was also associated with microsatellite instability (MSI\u2010H). No significant associations were observed between\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    presence or load and 10\u2010year overall, disease\u2010free, and cancer\u2010specific survival. A high\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    intratumoral burden was associated with aggressive tumor architecture characterized by PDC in stage II CRC. Nevertheless, no impact on long\u2010term clinical outcomes was observed, indicating that\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    had limited prognostic value.\n                  <\/jats:p>","DOI":"10.1111\/apm.70225","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T08:55:44Z","timestamp":1779353744000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor\u2010Associated\n                    <scp>\n                      <i>Fusobacterium nucleatum<\/i>\n                    <\/scp>\n                    and Aggressive Architectural Features in Stage\n                    <scp>II<\/scp>\n                    Colorectal Cancer"],"prefix":"10.1111","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5809-4471","authenticated-orcid":false,"given":"Mariana Bisarro","family":"dos Reis","sequence":"first","affiliation":[{"name":"Molecular Oncology Research Center Barretos Cancer Hospital  Barretos Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monise Tadin","family":"Reis","sequence":"additional","affiliation":[{"name":"Molecular Oncology Research Center Barretos Cancer Hospital  Barretos Brazil"},{"name":"Department of Pathology Barretos Cancer Hospital  Barretos Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Department of Pathology Barretos Cancer Hospital  Barretos Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo Noriz","family":"Berardinelli","sequence":"additional","affiliation":[{"name":"Molecular Diagnostic Laboratory Barretos Cancer Hospital  Barretos Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana Camacho","family":"Cheregatto","sequence":"additional","affiliation":[{"name":"Molecular Oncology Research Center Barretos Cancer Hospital  Barretos Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Welinton","family":"Hirai","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics Barretos Cancer Hospital  Barretos Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valiana","family":"Teodoro","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics Barretos Cancer Hospital  Barretos Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise Peixoto","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Molecular Oncology Research Center Barretos Cancer Hospital  Barretos Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9639-7940","authenticated-orcid":false,"given":"Rui Manuel","family":"Reis","sequence":"additional","affiliation":[{"name":"Molecular Oncology Research Center Barretos Cancer Hospital  Barretos Brazil"},{"name":"Molecular Diagnostic Laboratory Barretos Cancer Hospital  Barretos Brazil"},{"name":"Life and Health Sciences Research Institute (ICVS), Medical School University of Minho  Braga Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/EDBK_438466"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fsurg.2021.666400"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-021-01441-4"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.612826"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-72687-3"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2016.274"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-00866-x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2017.46"},{"issue":"1","key":"e_1_2_11_11_1","first-page":"346","article-title":"Tissue\u2010Resident Microbiota Impacts Colorectal Cancer Progression and Prognosis","volume":"17","author":"Shi Z.","year":"2025","journal-title":"NatureCommunications"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0209-8"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2023.03.205"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000512175"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2022.08.010"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics12010114"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00813"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.15361"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-018-0230-7"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2018.1"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.00264"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2025.08.005"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.11.041"},{"issue":"9","key":"e_1_2_11_24_1","article-title":"Cellular and Molecular Mechanisms of the Tumor Stroma in Colorectal Cancer: Insights Into Disease Progression and Therapeutic Targets","volume":"11","author":"Shakhpazyan N.","year":"2023","journal-title":"Biomedicine"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s42047-025-00196-2"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00145"},{"key":"e_1_2_11_27_1","first-page":"635","volume-title":"WHO Classification of Tumours. Digestive System Tumours Lyon, 2019","author":"WHO Classification of Tumours Editorial Board","year":"2019"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics12010114"},{"issue":"3","key":"e_1_2_11_29_1","first-page":"402","article-title":"Tumor Budding and Poorly\u2010Differentiated Cluster in Prognostication in Stage II Colon Cancer","volume":"214","author":"Lee V. W. K.","year":"2018","journal-title":"Pathology"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.15215"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.4251\/wjgo.v11.i10.898"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5998"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05435-0"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15233"},{"issue":"1","key":"e_1_2_11_35_1","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1186\/s13046-023-02817-8","article-title":"Fusobacterium nucleatum\n                  \u2010triggered neutrophil extracellular traps facilitate colorectal carcinoma progression","volume":"42","author":"Kong X.","year":"2023","journal-title":"Journal of Experimental & Clinical Cancer Research: CR"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0155-3"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2017.32.10.1595"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-018-6681-5"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-310101"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastha.2025.100644"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-017-1382-6"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.07.008"}],"container-title":["APMIS"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apm.70225","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/apm.70225","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apm.70225","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T03:53:04Z","timestamp":1779767584000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apm.70225"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":41,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1111\/apm.70225"],"URL":"https:\/\/doi.org\/10.1111\/apm.70225","archive":["Portico"],"relation":{},"ISSN":["0903-4641","1600-0463"],"issn-type":[{"value":"0903-4641","type":"print"},{"value":"1600-0463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2026-02-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70225"}}