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Despite the appealing role of necroptosis as an alternative cell death pathway in cancer pathogenesis, its relevance to pituitary adenoma pathogenesis has yet to be determined that is perused in the current study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The total number of 109 specimens including pituitary adenomas and cadaveric healthy pituitary tissues were enrolled in the current study. Tumor and healthy pituitary tissues were subjected to RNA extraction and gene analysis using Real-Time PCR. The expression levels of necroptosis markers (RIP1K, RIP3K and, MLKL) and their association with the patient\u2019s demographic features were evaluated, also the protein level of MLKL was assessed using immunohistochemistry in tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Based on our data, the remarkable reduction in RIP3K and MLKL expression were detected in nonfunctional and GH-secreting pituitary tumors compared to pituitary normal tissues. Invasive tumors revealed lower expression of RIP3K and MLKL compared to non-invasive tumors, also the attenuated level of MLKL was associated with the tumor size in invasive NFPA. The simultaneous down-regulation of MLKL protein in pituitary adenoma tissues was observed which was in line with its gene expression. While, RIP1K over-expressed significantly in both types of pituitary tumors which showed no significant correlation with patient\u2019s age, gender and tumor size in GHPPA and NFPA group. Notably, MLKL and RIP3K gene expression was significantly correlated in the GHPPA group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>According to our data, the reduced expression of necroptosis mediators (RIP3K, MLKL) in pituitary adenoma reinforces the hypothesis that the necroptosis pathway can be effective in regulating the proliferation and growth of pituitary tumor cells and tumor recurrence.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12902-021-00919-y","type":"journal-article","created":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T06:03:29Z","timestamp":1641276209000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Evaluation of the expression of necroptosis pathway mediators and its association with tumor characteristics in functional and non-functional pituitary adenomas"],"prefix":"10.1186","volume":"22","author":[{"given":"Mohammad E.","family":"Khamseh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alireza","family":"Sheikhi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zahra","family":"Shahsavari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Ghorbani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamideh","family":"Akbari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehrnaz","family":"Imani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahshid","family":"Panahi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alimohammad","family":"Alimohammadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryam","family":"Ameri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shima","family":"Nazem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vahid","family":"Salimi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4449-9248","authenticated-orcid":false,"given":"Masoumeh","family":"Tavakoli-Yaraki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,1,4]]},"reference":[{"issue":"3","key":"919_CR1","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1002\/cncr.20412","volume":"101","author":"S Ezzat","year":"2004","unstructured":"Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML, et al. 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All patients were informed before surgery and they were provided with written informed consent for participation. In the consent form, they were informed that their tumor tissues will be collected and used for this study. Following their agreement to participate in the study and signed consent form, they were included in the survey. For each patient the written informed consent is available. The healthy pituitary tissues were collected from the Legal Medicine Organization (LMO), Tehran, Iran following the required ethical approval which was needed for the organization. The first-degree relatives of deceased individuals were informed and provided with a written consent form, indicating a collection of normal pituitary autopsies and following their agreement and signed consent form, the normal pituitary tissues were collected. Also, all methods were carried out under relevant guidelines and regulations.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The consent for publication is not required since no personal or identifying information of participants are contained within the manuscript or supplementary materials.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that there is no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1"}}