{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:00:13Z","timestamp":1790398813741,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The Stroma AReactive Invasion Front Areas (SARIFA) is a novel histological phenomenon characterized by direct tumour cell\u2010adipocyte interaction without intervening stroma or inflammatory cells and easily identifiable in routine haematoxylin\u2013eosin\u2010stained sections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study evaluated the prognostic significance of SARIFA in a cohort consisting of 333 gastric cancer patients, including 171 intestinal and 162 non\u2010intestinal adenocarcinoma cases. Associations between SARIFA and various well\u2010known histopathological tumour parameters, including lymphovascular invasion, perineural invasion, tumour budding and poorly differentiated clusters (PDCs), were investigated and the prognostic value of these features for survival was determined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SARIFA was more frequently observed in non\u2010intestinal carcinomas but was significantly associated with lymphovascular and perineural invasion in both gastric cancer subtypes. Number of SARIFA foci showed a weak positive correlation with the number of tumour buds and PDCs. SARIFA was identified as an independent negative prognostic factor for overall survival in non\u2010intestinal gastric cancers. According to time\u2010dependent ROC curve analysis, quantification of SARIFA foci did not increase the prognostic accuracy beyond detecting their absence or presence in both gastric cancer subtypes. In addition, the lymph node ratio in both subcohorts and perineural invasion in intestinal adenocarcinomas were also found to be independent prognostic factors for overall survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SARIFA is a robust, easily assessable histological marker with independent prognostic value in non\u2010intestinal gastric adenocarcinomas. Reliable histopathological markers for this group of tumours, characterized by their distinctive morphology and infiltration pattern, remain limited. Integration of SARIFA into routine diagnostics may enhance risk stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/his.70289","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:32:32Z","timestamp":1790397152000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Stroma\n                    <scp>AReactive<\/scp>\n                    Invasion Front Areas (SARIFA) is a negative prognostic factor for overall survival in non\u2010intestinal gastric adenocarcinomas"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4825-9057","authenticated-orcid":false,"given":"\u00c1kos","family":"Jakab","sequence":"first","affiliation":[{"name":"Department of Pathology, Forensic and Insurance Medicine Semmelweis University  Budapest Hungary"},{"name":"Department of Pathology and Experimental Cancer Research Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9784-2439","authenticated-orcid":false,"given":"Luca","family":"Szalai","sequence":"additional","affiliation":[{"name":"Department of Pathology, Forensic and Insurance Medicine Semmelweis University  Budapest Hungary"},{"name":"Department of Surgical and Molecular Pathology, Centre of Tumour Pathology National Institute of Oncology  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Zeng\u0151","sequence":"additional","affiliation":[{"name":"Department of Pathology, Forensic and Insurance Medicine Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8031-2463","authenticated-orcid":false,"given":"Ildik\u00f3","family":"Kocsm\u00e1r","sequence":"additional","affiliation":[{"name":"Department of Pathology, Forensic and Insurance Medicine Semmelweis University  Budapest Hungary"},{"name":"Department of Urology Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8126-3982","authenticated-orcid":false,"given":"Tibor","family":"V\u00e1rkonyi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Forensic and Insurance Medicine Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6963-8489","authenticated-orcid":false,"given":"Istv\u00e1n","family":"Kenessey","sequence":"additional","affiliation":[{"name":"Department of Pathology, Forensic and Insurance Medicine Semmelweis University  Budapest Hungary"},{"name":"National Cancer Registry National Institute of Oncology  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3768-4912","authenticated-orcid":false,"given":"Attila","family":"Szij\u00e1rt\u00f3","sequence":"additional","affiliation":[{"name":"Department of Surgery, Transplantation and Gastroenterology Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7453-3163","authenticated-orcid":false,"given":"Andr\u00e1s","family":"Kiss","sequence":"additional","affiliation":[{"name":"Department of Pathology, Forensic and Insurance Medicine Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9078-5558","authenticated-orcid":false,"given":"Tam\u00e1s","family":"Vass","sequence":"additional","affiliation":[{"name":"Department of Surgery, Transplantation and Gastroenterology Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6921-8978","authenticated-orcid":false,"given":"G\u00e1bor","family":"Lotz","sequence":"additional","affiliation":[{"name":"Department of Pathology, Forensic and Insurance Medicine Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3061-1323","authenticated-orcid":false,"given":"\u00c9va","family":"Kocsm\u00e1r","sequence":"additional","affiliation":[{"name":"Department of Pathology, Forensic and Insurance Medicine Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"e_1_2_12_2_1","first-page":"394","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray F","year":"2018","journal-title":"CA Cancer J. 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Lab Med."},{"key":"e_1_2_12_9_1","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1158\/1055-9965.EPI-09-0250","article-title":"Stomach carcinoma incidence patterns in the United States by histologic type and anatomic site","volume":"18","author":"Wu H","year":"2009","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"e_1_2_12_10_1","doi-asserted-by":"crossref","first-page":"290","DOI":"10.5858\/2005-129-290-DTITIA","article-title":"Differential trends in the intestinal and diffuse types of gastric carcinoma","volume":"129","author":"Sidoni A","year":"2005","journal-title":"Arch. Pathol. Lab Med."},{"key":"e_1_2_12_11_1","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.3389\/fonc.2020.01212","article-title":"Analysis of the incidence and survival of gastric cancer based on the Lauren classification: A large population\u2010based study using SEER","volume":"10","author":"Tang C\u2010T","year":"2020","journal-title":"Front. Oncol."},{"key":"e_1_2_12_12_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1097\/PAS.0000000000001181","article-title":"Tumor budding and prognosis in gastric adenocarcinoma","volume":"43","author":"Kemi N","year":"2019","journal-title":"Am. J. Surg. Pathol."},{"key":"e_1_2_12_13_1","doi-asserted-by":"crossref","first-page":"4731","DOI":"10.3390\/cancers14194731","article-title":"Prognostic ability of tumor budding outperforms poorly differentiated clusters in gastric cancer","volume":"14","author":"Szalai L","year":"2022","journal-title":"Cancers (Basel)"},{"key":"e_1_2_12_14_1","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1177\/10668969221105617","article-title":"Prognostic significance of tumour budding and desmoplastic reaction in intestinal\u2010type gastric adenocarcinoma","volume":"31","author":"Pun C","year":"2023","journal-title":"Int. J. Surg. Pathol."},{"key":"e_1_2_12_15_1","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1038\/modpathol.2017.46","article-title":"Recommendations for reporting tumor budding in colorectal cancer based on the international tumor budding consensus conference (ITBCC) 2016","volume":"30","author":"Lugli A","year":"2017","journal-title":"Mod. Pathol."},{"key":"e_1_2_12_16_1","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1093\/annonc\/mdt593","article-title":"The relationship between tumour stroma percentage, the tumour microenvironment and survival in patients with primary operable colorectal cancer","volume":"25","author":"Park JH","year":"2014","journal-title":"Ann. Oncol."},{"key":"e_1_2_12_17_1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1093\/annonc\/mds246","article-title":"The proportion of tumor\u2010stroma as a strong prognosticator for stage II and III colon cancer patients: Validation in the VICTOR trial","volume":"24","author":"Huijbers A","year":"2013","journal-title":"Ann. 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Cancer"},{"key":"e_1_2_12_25_1","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s00428-024-03826-4","article-title":"Stroma AReactive invasion front areas (SARIFA) predict poor survival in adenocarcinomas of the stomach and gastrooesophageal junction: A validation study","volume":"485","author":"Ulase D","year":"2024","journal-title":"Virchows Arch."},{"key":"e_1_2_12_26_1","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/s41416-023-02515-4","article-title":"Stroma AReactive invasion front areas (SARIFA) improves prognostic risk stratification of perioperative chemotherapy treated oesophagogastric cancer patients from the MAGIC and the ST03 trial","volume":"130","author":"Grosser B","year":"2024","journal-title":"Br. J. 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Res."},{"key":"e_1_2_12_28_1","doi-asserted-by":"crossref","first-page":"731","DOI":"10.5009\/gnl220254","article-title":"The Clinicopathological features of mixed carcinoma in 7,215 patients with gastric cancer in a tertiary Hospital in South Korea","volume":"17","author":"Jo HH","year":"2023","journal-title":"Gut Liver"},{"key":"e_1_2_12_29_1","volume-title":"TNM classification of malignant Tumours","author":"Brierley J","year":"2025"},{"key":"e_1_2_12_30_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1097\/SLA.0000000000002040","article-title":"Lauren histologic type is the Most important factor associated with pattern of recurrence following resection of gastric adenocarcinoma","volume":"267","author":"Lee JH","year":"2018","journal-title":"Ann. 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