{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T04:06:58Z","timestamp":1768795618457,"version":"3.49.0"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>TFF1 expression is markedly reduced in human GCs, suggesting that TFF1 is a tumor suppressor for human gastric cancer. The present study evaluated the expression and distribution pattern of TFF1 in paraffin-embedded canine gastric tissue samples, including normal mucosa (n = 3), polyps (n = 8), carcinomas (n = 31) and their adjacent non-neoplastic mucosa (n = 30), neoplastic emboli (n = 14), and metastatic lesions (n = 9), by immunohistochemistry (IHC). All normal gastric tissues expressed TFF1 in the superficial foveolar epithelium and mucopeptic cells of the neck region. Most gastric polyps (GPs) displayed immunoreactivity for TFF1 in &gt;75% of the epithelial component. In GCs, the expression of TFF1 was found reduced in 74.2% of the cases. The level of TFF1 expression had a decreased tendency from normal gastric mucosa to GPs and GCs (p &lt; 0.05). No significant differences in the expression of TFF1 were found in GCs, according to age, sex, histological type based on World Health Organization (WHO) and Lauren classification, tumor location, depth of tumor invasion, presence of neoplastic emboli or metastatic lesions. The median survival time of GC patients with preserved and reduced TFF1 immunoexpression were 30 and 12 days, respectively. Kaplan\u2013Meier analysis revealed no significant survival differences between the two groups (p &gt; 0.05). These findings suggest that TFF1 protein may play a role in canine gastric carcinogenesis, and further studies are necessary to define its usefulness as a prognostic indicator in canine gastric carcinoma.<\/jats:p>","DOI":"10.3390\/ani11102855","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T00:03:42Z","timestamp":1632960222000},"page":"2855","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Immunoexpression of Trefoil Factor 1 in Non-Neoplastic and Neoplastic Canine Gastric Tissues"],"prefix":"10.3390","volume":"11","author":[{"given":"Ana R.","family":"Flores","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Immunology of the Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"},{"name":"Institute of Pathology and Molecular Immunology of the University of Porto (IPATIMUP), 4200-465 Porto, Portugal"},{"name":"Animal and Veterinary Research Center (CECAV), Associate Laboratory AL4AnimalS, University of Tr\u00e1s-os-Montes e Alto Douro (UTAD), 5001-801 Vila Real, Portugal"}]},{"given":"Marisa","family":"Castro","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Immunology of the Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Alexandra","family":"R\u00eama","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Immunology of the Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8769-8103","authenticated-orcid":false,"given":"Jo\u00e3o R.","family":"Mesquita","sequence":"additional","affiliation":[{"name":"Epidemiology Research Unit (EPIUnit), Instituto de Sa\u00fade P\u00fablica da Universidade do Porto (ISPUP), 4050-600 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8987-6038","authenticated-orcid":false,"given":"Marian","family":"Taulescu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania"},{"name":"Synevovet Laboratory, 81 Pache Protopopescu, 021408 Bucharest, Romania"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5302-0086","authenticated-orcid":false,"given":"F\u00e1tima","family":"G\u00e4rtner","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Immunology of the Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"},{"name":"Institute of Pathology and Molecular Immunology of the University of Porto (IPATIMUP), 4200-465 Porto, Portugal"},{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1912-1457","authenticated-orcid":false,"given":"Fernanda","family":"Seixas","sequence":"additional","affiliation":[{"name":"Animal and Veterinary Research Center (CECAV), Associate Laboratory AL4AnimalS, University of Tr\u00e1s-os-Montes e Alto Douro (UTAD), 5001-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2305-1631","authenticated-orcid":false,"given":"Irina","family":"Amorim","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Immunology of the Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"},{"name":"Institute of Pathology and Molecular Immunology of the University of Porto (IPATIMUP), 4200-465 Porto, Portugal"},{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jcpa.2015.10.181","article-title":"Canine Gastric Pathology: A Review","volume":"154","author":"Amorim","year":"2016","journal-title":"J. Comp. Pathol."},{"key":"ref_2","first-page":"269","article-title":"Intestinal Metaplasia and Over-Expression of c-erb2 and p53 in Tissue Adjacent to Dog Gastric Carcinoma","volume":"37","author":"Gualtieri","year":"2017","journal-title":"Pak. Vet. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1111\/vsu.13239","article-title":"Perioperative complications and outcome after surgery for treatment of gastric carcinoma in dogs: A Veterinary Society of Surgical Oncology retrospective study of 40 cases (2004\u20132018)","volume":"48","author":"Abrams","year":"2019","journal-title":"Vet. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Head, K.W., Cullen, J.M., Dubielzig, R.R., Else, R.W., Misdorp, W., Patnaik, A.K., Tateyama, S., and van der Gaag, I. (2003). Histological Classification of Tumors of the Alimentary System of Domestic Animals, Armed Forces Institute of Pathology.","DOI":"10.1002\/9780470376928.ch8"},{"key":"ref_5","first-page":"396","article-title":"Risk and characteristics of gastric carcinoma in the chow chow dog","volume":"61","author":"Koterbay","year":"2020","journal-title":"Can. Vet. J."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Watanabe, H., Jass, J., Sobin, L., Ota, K., and Jass, J. (1990). Histological typing of oesophageal and gastric tumours. WHO International Histological Classification of Tumours, Springer. [2nd ed.].","DOI":"10.1007\/978-3-642-83920-7"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1177\/030098587801500503","article-title":"Canine gastric adenocarcinoma","volume":"15","author":"Patnaik","year":"1978","journal-title":"Vet. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1111\/j.1748-5827.1989.tb01579.x","article-title":"Gastric carcinoma in the dog: A clinicopathological study of 11 cases","volume":"30","author":"Fonda","year":"1989","journal-title":"J. Small Anim. Pract."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1177\/0300985810363700","article-title":"The novel carbohydrate tumor antigen C2-O-sLe x is upregulated in canine gastric carcinomas","volume":"47","author":"Janke","year":"2010","journal-title":"Vet. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1111\/vco.12586","article-title":"Tn and Sialyl-Tn antigens in canine gastric tissues","volume":"18","author":"Flores","year":"2020","journal-title":"Veter-Comp. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/1097-0142(19930715)72:2<323::AID-CNCR2820720204>3.0.CO;2-G","article-title":"Hyperplastic polyposis and diffuse carcinoma of the stomach. A study of a family","volume":"72","author":"Carneiro","year":"1993","journal-title":"Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1097\/00008469-199606000-00005","article-title":"Pattern of pS2 protein expression in premalignant and malignant lesions of gastric mucosa","volume":"5","author":"Machado","year":"1996","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1111\/j.1748-5827.2012.01291.x","article-title":"Gastric carcinoma associated with Menetrier\u2019s-like disease in a West Highland white terrier","volume":"53","author":"Lecoindre","year":"2012","journal-title":"J. Small Anim. Pract."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.jcpa.2008.07.001","article-title":"Gastric neuroendocrine carcinoma associated with atrophic gastritis in the norwegian lundehund","volume":"139","author":"Qvigstad","year":"2008","journal-title":"J. Comp. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1177\/0300985812439076","article-title":"M\u00e9n\u00e9trier disease and gastric adenocarcinoma in 3 Cairn terrier littermates","volume":"49","author":"Munday","year":"2012","journal-title":"Vet. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1186\/s13000-014-0166-z","article-title":"An immunohistochemical study of canine spontaneous gastric polyps","volume":"9","author":"Amorim","year":"2014","journal-title":"Diagn. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1146\/annurev-physiol-021115-105447","article-title":"Trefoil Factor Peptides and Gastrointestinal Function","volume":"79","author":"Aihara","year":"2017","journal-title":"Annu. Rev. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1515\/bmc-2015-0020","article-title":"Trefoil factor family peptides\u2014Friends or foes?","volume":"6","author":"Busch","year":"2015","journal-title":"Biomol. Concepts"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7895","DOI":"10.1093\/nar\/10.24.7895","article-title":"Cloning of cDNA sequences of hormone-regulated genes from the MCF-7 human breast cancer cell line","volume":"10","author":"Masiakowski","year":"1982","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1007\/s000180050108","article-title":"Trefoil peptides: From structure to function","volume":"53","author":"Thim","year":"1997","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1126\/science.3041593","article-title":"Breast cancer-associated pS2 protein: Synthesis and secretion by normal stomach mucosa","volume":"241","author":"Rio","year":"1988","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1083\/jcb.122.1.191","article-title":"The mouse one P-domain (pS2) and two P-domain (mSP) genes exhibit distinct patterns of expression","volume":"122","author":"Lefebvre","year":"1993","journal-title":"J. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/(SICI)1096-9896(199709)183:1<4::AID-PATH1099>3.0.CO;2-5","article-title":"Trefoil proteins: Their role in normal and malignant cells","volume":"183","author":"May","year":"1997","journal-title":"J. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1126\/science.274.5285.259","article-title":"Gastric mucosa abnormalities and tumorigenesis in mice lacking the pS2 trefoil protein","volume":"274","author":"Lefebvre","year":"1996","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1016\/0959-8049(96)00116-5","article-title":"pS2 protein expression in gastric carcinoma. An immunohistochemical and immunoradiometric study","volume":"32","author":"Machado","year":"1996","journal-title":"Eur. J. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1002\/path.1711710406","article-title":"pS2 protein in gastric carcinoma and normal gastric mucosa: Association with clincopathological parameters and patient survival","volume":"171","author":"Borchard","year":"1993","journal-title":"J. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1002\/ijc.2910440510","article-title":"Expression of the pS2 gene in normal, benign and neoplastic human stomach","volume":"44","author":"Luqmani","year":"1989","journal-title":"Int. J. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.3892\/or.2012.1939","article-title":"Role of trefoil factor 1 in gastric cancer and relationship between trefoil factor 1 and gastrokine 1","volume":"28","author":"Mao","year":"2012","journal-title":"Oncol. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.rvsc.2007.08.008","article-title":"Canine and feline trefoil factor family peptides: Highly conserved molecules with some unique characteristics","volume":"85","author":"Campbell","year":"2008","journal-title":"Res. Vet. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.vetimm.2012.10.009","article-title":"Expression of trefoil factor genes in the duodenum and colon of dogs with inflammatory bowel disease and healthy dogs","volume":"151","author":"Schmitz","year":"2013","journal-title":"Veter-Immunol. Immunopathol."},{"key":"ref_31","unstructured":"Bosman, F.T., Carneiro, F., Hruban, R.H., and Theise, N.D. (2010). WHO Classification of Tumors of the Digestive System, IARC Press."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/apm.1965.64.1.31","article-title":"The Two Histological Main Types of Gastric Carcinom: Diffuse and So-Called Intestinal-Type Carcinoma. An Attempt at a Histo-Clinical Classification","volume":"64","author":"Lauren","year":"1965","journal-title":"Acta Pathol. Microbiol. Scand."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"139","DOI":"10.4142\/jvs.2007.8.2.139","article-title":"Diagnosis of Helicobacter spp. infection in canine stomach","volume":"8","author":"Prachasilpchai","year":"2007","journal-title":"J. Veter-Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1002\/(SICI)1096-9896(199904)187:5<541::AID-PATH283>3.0.CO;2-9","article-title":"Patterns of expression of trefoil peptides and mucins in gastric polyps with and without malignant transformation","volume":"187","author":"Nogueira","year":"1999","journal-title":"J. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Terragni, R., Casadei Gardini, A., Sabattini, S., Bettini, G., Amadori, D., Talamonti, C., Vignoli, M., Capelli, L., Saunders, J.H., and Ricci, M. (2014). EGFR, HER-2 and KRAS in canine gastric epithelial tumors: A potential human model?. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085388"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1177\/0300985810375050","article-title":"Canine gastric carcinoma: Immunohistochemical expression of cell cycle proteins (p53, p21, and p16) and heat shock proteins (Hsp27 and Hsp70)","volume":"48","author":"Carrasco","year":"2011","journal-title":"Vet. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"157","DOI":"10.5326\/0380157","article-title":"Canine gastric adenocarcinoma and leiomyosarcoma: A retrospective study of 21 cases (1986\u20131999) and literature review","volume":"38","author":"Swann","year":"2002","journal-title":"J. Am. Anim. Hosp. Assoc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1136\/gut.2003.031963","article-title":"Trefoil factor 1 is required for the commitment programme of mouse oxyntic epithelial progenitors","volume":"53","author":"Karam","year":"2004","journal-title":"Gut"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7361","DOI":"10.3748\/wjg.v12.i45.7361","article-title":"Molecular forms of trefoil factor 1 in normal gastric mucosa and its expression in normal and abnormal gastric tissues","volume":"12","author":"Ren","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4161","DOI":"10.1158\/1078-0432.CCR-07-4381","article-title":"Decreased expression of gastrokine 1 and the trefoil factor interacting protein TFIZ1\/GKN2 in gastric cancer: Influence of tumor histology and relationship to prognosis","volume":"14","author":"Moss","year":"2008","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/j.1349-7006.1998.tb00559.x","article-title":"Loss of pS2 protein expression is an early event of intestinal-type gastric cancer","volume":"89","author":"Wu","year":"1998","journal-title":"Jpn. J. Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"133","DOI":"10.7150\/ijms.5500","article-title":"Reduced expression of TFF1 and increased expression of TFF3 in gastric cancer: Correlation with clinicopathological parameters and prognosis","volume":"10","author":"Im","year":"2013","journal-title":"Int. J. Med. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"894","DOI":"10.3892\/ijo.2013.1759","article-title":"Loss of trefoil factor 1 is regulated by DNA methylation and is an independent predictive factor for poor survival in advanced gastric cancer","volume":"42","author":"Tanaka","year":"2013","journal-title":"Int. J. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.pan.2017.07.188","article-title":"Trefoil factor family 1 expression in the invasion front is a poor prognostic factor associated with lymph node metastasis in pancreatic cancer","volume":"17","author":"Sunagawa","year":"2017","journal-title":"Pancreatology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"32","DOI":"10.20517\/2394-4722.2017.78","article-title":"Circulating tumor cells in gastric cancer","volume":"4","author":"Nakamura","year":"2018","journal-title":"J. Cancer Metastasis Treat."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3892\/mmr.2013.1772","article-title":"DNA methylation of trefoil factor 1 (TFF1) is associated with the tumorigenesis of gastric carcinoma","volume":"9","author":"Feng","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3119","DOI":"10.3748\/wjg.v12.i19.3119","article-title":"Expression of trefoil factors 1 and 2 in precancerous condition and gastric cancer","volume":"12","author":"Shi","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1177\/172460080101600105","article-title":"Prognostic significance of cytosolic pS2 protein content in gastric cancer","volume":"16","author":"Vizoso","year":"2001","journal-title":"Int. J. Biol. Markers"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jcpa.2010.11.007","article-title":"CDX-2 and HER-3 expression in canine gastric and colorectal adenocarcinomas","volume":"145","author":"Doster","year":"2011","journal-title":"J. Comp. Pathol."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/11\/10\/2855\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:07:34Z","timestamp":1760166454000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/11\/10\/2855"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,29]]},"references-count":49,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["ani11102855"],"URL":"https:\/\/doi.org\/10.3390\/ani11102855","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,29]]}}}