{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T21:18:33Z","timestamp":1760908713298,"version":"3.40.4"},"reference-count":54,"publisher":"S. Karger AG","issue":"5","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathobiology"],"published-print":{"date-parts":[[2011]]},"abstract":"<i>Objective:<\/i> We aimed to evaluate the inactivation of <i>COX-2<\/i>, <i>HMLH1<\/i> and <i>CDKN2A<\/i> by promoter methylation and its relationship with the infection by different <i>Helicobacter pylori<\/i> strains in gastric cancer. <i>Methods:<\/i> DNA extracted from 76 <i>H. pylori<\/i>-positive gastric tumor samples was available for promoter methylation identification by methylation-specific PCR and <i>H. pylori<\/i> subtyping by PCR. Immunohistochemistry was used to determine COX-2, p16<sup>INK4A<\/sup> and HMLH1 expression. <i>Results:<\/i> A strong negative correlation was found between the expression of these markers and the presence of promoter methylation in their genes. Among cardia tumors, negativity of p16<sup>INK4A<\/sup> was a significant finding. On the other hand, in noncardia tumors, the histological subtypes had different gene expression patterns. In the intestinal subtype, a significant finding was <i>HMLH1<\/i> inactivation by methylation, while in the diffuse subtype, <i>CDKN2A<\/i> inactivation by methylation was the significant finding. Tumors with methylated <i>COX-2<\/i> and <i>HMLH1<\/i> genes were associated with <i>H. pylori vac<\/i>A s1 (p = 0.025 and 0.047, respectively), and the nonmethylated tumors were associated with the presence of the gene <i>fla<\/i>A. <i>Conclusions:<\/i> These data suggest that the inactivation of these genes by methylation occurs by distinct pathways according to the histological subtype and tumor location and depends on the <i>H. pylori<\/i> genotype.<\/jats:p>","DOI":"10.1159\/000329475","type":"journal-article","created":{"date-parts":[[2011,8,17]],"date-time":"2011-08-17T06:19:16Z","timestamp":1313561956000},"page":"266-276","source":"Crossref","is-referenced-by-count":31,"title":["Inactivation of <i>COX-2<\/i>, <i>HMLH1<\/i> and <i>CDKN2A<\/i> Gene by Promoter Methylation in Gastric Cancer: Relationship with Histological Subtype, Tumor Location and <i>Helicobacter pylori<\/i> Genotype"],"prefix":"10.1159","volume":"78","author":[{"given":"Mark\u00eania K\u00e9lia Santos","family":"Alves","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana Camargo","family":"Ferrasi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeska Portela","family":"Lima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e1rcia Val\u00e9ria Pitombeira","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria In\u00eas","family":"de Moura Campos Pardini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia Helena 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