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The study evaluates an association between the morphological appearance of endometrial hyperplasia and ECa, and the presence of PTEN variations, PTEN protein level and intracellular localization. A total of 67 archived formalin-fixed and paraffin-embedded human biopsy tissue specimens with normal proliferative and secretory endometrium, endometrial hyperplasia without atypia and endometrial atypical hyperplasia, endometrioid the grade G1 and G3 and serous subtype of ECa were evaluated by sequencing for the presence of mutations in coding regions of PTEN gene of endometrial epithelial cells. The PTEN gene expression and intercellular localization of PTEN protein were evaluated immunohistochemically by immunoreactive score (IRS). PTEN mutation spectrum in endometrial carcinoma was identified for Slovak population. Twenty-eight non-silent mutations were identified in PTEN, twelve of them being novel, not annotated in Catalogue of Somatic Mutations in Cancer. Higher frequency of PTEN mutations was observed in serous carcinoma compared to global average. No correlation was observed between samples IRS, PTEN cellular localization and identified mutations. PTEN sequencing can be beneficial for patients considering prognosis of disease and sensitivity to treatment.<\/jats:p>","DOI":"10.33549\/physiolres.935030","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T20:47:52Z","timestamp":1672433272000},"page":"S125-S135","source":"Crossref","is-referenced-by-count":7,"title":["PTEN mutations as predictive marker for the high-grade endometrial cancer development in slovak women"],"prefix":"10.33549","volume":"71","author":[{"given":"H","family":"Gbelcov\u00e1","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Gergely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"\u0160i\u0161ovsk\u00fd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u013d","family":"Straka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"B\u00f6hmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Pastor\u00e1kov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Su\u0161ienkov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Repisk\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Korbe\u013e","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u013d","family":"Danihel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Pri\u0161\u010d\u00e1kov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava, University Hospital Bratislava, Bratislava, Slovak Republic. petra.priscakova@fmed.uniba.sk"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"19169","reference":[{"key":"ref0","doi-asserted-by":"publisher","unstructured":"Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. 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Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 1983; 15:10-17. https:\/\/doi.org\/10.1016\/0090-8258(83)90111-7","DOI":"10.1016\/0090-8258(83)90111-7"},{"key":"ref7","unstructured":"Herrington CS, Board WC of TE. Female Genital Tumours. International Agency for Research on Cancer; 2020."},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Masood M, Singh N. Endometrial carcinoma: changes to classification (WHO 2020). Diagnostic Histopathol 2021. https:\/\/doi.org\/10.1016\/j.mpdhp.2021.09.003","DOI":"10.1016\/j.mpdhp.2021.09.003"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Stavropoulos A, Varras M, Vasilakaki T, Varra VK, Tsavari A, Varra FN, Nonni A, Kavantzas N, Lazaris AC. Expression of p53 and PTEN in human primary endometrial carcinomas: Clinicopathological and immunohistochemical analysis and study of their concomitant expression. 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Cancer Res 2008; 68:1723-1731. https:\/\/doi.org\/10.1158\/0008-5472.CAN-07-1963","DOI":"10.1158\/0008-5472.can-07-1963"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Gbelcov\u00e1 H, Bake\u0161 P, Pri\u0161\u010d\u00e1kov\u00e1 P, \u0160i\u0161ovsk\u00fd V, Hojs\u00edkov\u00e1 I, Straka L, Kone\u010dn\u00fd M, Markus J, D'Acunto CW, Ruml T, B\u00f6hmer D, Danihel L, et al. PTEN sequence analysis in endometrial hyperplasia and endometrial carcinoma in Slovak women. Anal Cell Pathol 2015; 2015:746856. https:\/\/doi.org\/10.1155\/2015\/746856","DOI":"10.1155\/2015\/746856"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Travaglino A, Raffone A, Saccone G, Insabato L, Mollo A, De Placido G, Zullo F. PTEN as a predictive marker of response to conservative treatment in endometrial hyperplasia and early endometrial cancer. A systematic review and meta-analysis. 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