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We tried to confirm the role of <jats:italic>EPM2 AIP1<\/jats:italic> immunohistochemistry as a surrogate of <jats:italic>MLH1<\/jats:italic> promoter methylation in EC. Case series from two different institutions were analyzed by comparable methods using immunohistochemistry for MMR proteins and <jats:italic>EPM2 AIP1,<\/jats:italic> and pyrosequencing for <jats:italic>MLH1<\/jats:italic> methylation. In the first series of 70 cases, concordance was 100%, after reassessing three cases with methylation scores close to cut-off, by tumor cell enrichment. In the second series of 29 <jats:italic>MLH1<\/jats:italic>-deficient ECs, concordance was 96.5%, while in the control group of 30 MMR-proficient EC, one <jats:italic>MLH1<\/jats:italic>-positive case was <jats:italic>EPM2 AIP1<\/jats:italic>-negative. <jats:italic>EPM2 AIP1<\/jats:italic> immunoreactivity was qualitatively superior in curettages and biopsies compared to hysterectomy. We conclude that <jats:italic>EPM2 AIP1<\/jats:italic> immunohistochemistry is a good surrogate for <jats:italic>MLH1<\/jats:italic> promoter methylation analysis, cost-effective with short turnaround time, but needs attention regarding preanalytical handling, normal tissue contamination, or low tumor percentage.<\/jats:p>","DOI":"10.1007\/s00428-025-04132-3","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T22:04:40Z","timestamp":1749074680000},"page":"511-522","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["EPM2 AIP1 immunohistochemistry as a surrogate of promoter methylation analysis in endometrial carcinoma"],"prefix":"10.1007","volume":"487","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1636-6010","authenticated-orcid":false,"given":"Sonia","family":"Gatius","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Vaquero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Scheiber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Velasco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolors","family":"Cuevas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Kashofer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Santacana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00faria","family":"Eritja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigurd","family":"Lax","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Matias-Guiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"key":"4132_CR1","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1111\/his.12053","volume":"62","author":"X Matias-Guiu","year":"2013","unstructured":"Matias-Guiu X, Prat J (2013) Molecular pathology of endometrial carcinoma. 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