{"paper_id":"6296d8cf-1d0a-44f6-a121-e7aded9a14ae","body_text":"97\nCopyright by authors. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), \nwhich permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.\nFolia Medica 66(1):97-103\nDOI: 10.3897/folmed.66.e112757\nOriginal Article\nExpression of HIF-1α, Ki67, SMA  \nand E-Cadherin in Endometriosis, Endometrial \nand Ovarian Carcinoma\nDaniel Markov1, Elena Poryazova1, Ralitsa Raycheva2, Galabin Markov3 \n1 Department of General and Clinical Pathology, Faculty of Medicine, Medical University of Plovdiv, Plovdiv, Bulgaria \n2 Department of Social Medicine and Public Health, Faculty of Public Health, Medical University of Plovdiv, Plovdiv, Bulgaria\n3 Faculty of Medicine, Medical University of Plovdiv, Plovdiv, Bulgaria\nCorresponding author: Daniel Markov, Department of General and Clinical Pathology, Faculty of Medicine, Medical University of Plovdiv, 15A Vassil \nAprilov Blvd., 4002 Plovdiv, Bulgaria; Email: daniel_mark@abv.bg\nReceived: 14 Sep 2023 ♦ Accepted: 10 Nov 2023 ♦ Published: 29 Feb 2024\nCitation: Markov D, Poryazova E, Raycheva R, Markov G. Expression of HIF-1α, Ki67, SMA and E-cadherin in endometriosis, endo-\nmetrial and ovarian carcinoma. Folia Med (Plovdiv) 2024;66(1):97-103. doi: 10.3897/folmed.66.e112757.\nAbstract\nIntroduction: Endometriosis is a benign gynecological condition that shares many characteristics with cancer cells, including immune \nevasion, survival, adhesion, invasion, and angiogenesis. The simultaneous investigation of tissue hypoxia, EMT, and proliferative index \nin endometriosis, endometrial, and ovarian carcinomas may provide new insight into the evolution and progression of gynecological \nneoplasms.\nAim: The aim of our study was to follow the immunohistochemical expression in endometriosis, endometrial and ovarian carcinoma in \nrelation to tissue hypoxia and necrosis, EMT, proliferative index, and fibrosis.\nMaterials and methods:  The present study used biopsy samples from 50 patients with endometriosis, endometrial carcinoma, and \novarian carcinoma in search for a correlation between HIF-1α, Ki67, SMA, and E-cadherin expression and various clinicopathological \nfeatures.\nResults: We observed heterogeneity and different intensity of immunohistochemical expression in different groups of patients. Immu-\nnohistochemical expression was compared with the degree of tumor cell differentiation. Cells of poorly differentiated adenocarcinomas \nshowed a higher proliferative index with Ki67, presence of epithelial-mesenchymal transition with reduced expression of E-cadherin \nwith stronger expression of HIF-1α. Regarding SMA in pelvic and ovarian endometriosis foci, we reported strong diffuse expression in \nstromal cells with marked fibrosis.\nConclusion: Understanding the mechanisms of carcinogenesis and progression of gynecological tumors and endometriosis is impor -\ntant for prognosis, response to therapy, and possibly better treatment of patients.\nKeywords\nendometriosis, endometrial carcinoma, hypoxia, immunohistochemistry, ovarian carcinoma\nINTRODUCTION \nOf women of reproductive age, 5% to 15% have endometri-\nosis, which is defined as the presence of endometrial glands \nand stroma outside the uterus. [1] Ovarian cancer has been \nshown to develop in 0.5%–1% of cases of ovarian endome-\ntriosis.[2] Clear cell carcinoma (CCC) is most commonly \nassociated with ovarian endometriosis. \n\n98\nD. Markov et al.\nFolia Medica I 2024 I Vol. 66 I No. 1\nEndometrial carcinoma is the most common gyneco -\nlogical malignancy. Pathologically, it is classified into two \ngroups, type I (endometrioid endometrial carcinoma) \nwhich accounts for 70%-80% of cases, and type II (non-en-\ndometrioid), including serous ones, and clear cell carcino -\nma.[3] Understanding the molecular alterations underlying \nthe endometrial carcinogenesis and progression may be \nhelpful in identifying new molecular therapeutic targets. \nThe current study sought to investigate the relationship \nbetween immunohistochemical expression of HIF-1α,  \nepithelial, mesenchymal, and proliferative markers and \nclinicopathological parameters in endometriosis, endome -\ntrial, and ovarian carcinomas. \nHypoxia-inducible factor-1 (HIF-1) expression can be a \nmarker of tissue hypoxia in solid tumors and can be used \nfor therapeutic purposes due to its role in the progression of \ngynecological neoplasms.[4] In the literature, the results for \nHIF-1α in gynecological cancers are not always consistent. \nHIF-1α is the master regulator of cellular adaptation to \nhypoxia. It is a heterodimeric transcription factor composed \nof the HIF-1α and HIF-1β subunits.[5] Elevated levels of HIF-\n1α are observed in a number of human malignancies and are \nassociated with metastatic potential and poor prognosis. \nDecreased expression of E-cadherin is associated with \npositive EMT in tumor tissue and with proliferation, pro -\ngression and metastasis, respectively, and a worse progno -\nsis. In such cases, the tumors usually also have a high pro -\nliferative index. \nAIM \nThe present study was conducted to investigate the correla-\ntion between HIF-1α expression in endometriosis and en -\ndometrial carcinomas by immunohistochemical technique. \nThe expression of HIF-1α, Ki67, SMA and E-cadherin was \nstudied and a comparative analysis of their expression was \nmade in the three studied groups. \nMATERIALS AND METHODS \nFifty patients were included in the current study and were \nevaluated both prospectively and retrospectively. All of \nthem are from the biopsy array of the Department of Clin-\nical Pathology of Pulmed University Hospital in Plovdiv \nfor a period of five years (2019-2023). DAKO antibodies \nwere used. \nAll patients were operated on and diagnosed in the Clin-\nic of Obstetrics and Gynecology of Pulmed University Hos-\npital of Plovdiv. The biopsy materials were reviewed by two \nindependent pathologists to diagnose, the morphological \ntype and stage the tumor according to FIGO. The histolog-\nical and immunohistochemical investigation of the biopsy \nmaterials was performed in the laboratory of the Morpho -\nlogical Center of the Department of General and Clinical \nPathology of the Medical University of Plovdiv. \nImmunohistochemical analysis \nThe tissue was treated with standard histopathological \ntechnique according to standard protocols, and semi-quan-\ntitative analysis of the results was performed. 4-μm thick \nparaffin sections were dewaxed and rehydrated through \ndescending alcohols. Hematoxylin-eosin staining was per -\nformed according to standard methods. The immunohis -\ntochemical study was performed according to standard \nprotocols. Immunohistochemistry was performed for the \nprotein markers HIF-1α, Ki67, SMA and E-cadherin. \nAn automatic immunostainer (Bond, DAKO) was used \nfollowing the manufacturer’s protocols. \nAntibodies produced by Dako, Denmark and Abcam, \nUSA were used: \n– rabbit monoclonal antibody against human HIF-1α, \n1:100 dilution  \nWe reported nuclear staining. \n– mouse monoclonal antibody against human E-cadherin \nWe reported cytoplasmic and membranous staining. \n– mouse monoclonal antibody against human Ki67 \nWe reported nuclear staining. \n– mouse monoclonal antibody against human SMA \nCytoplasmic and membranous staining were described. \nDAB was used as the chromogen. An automated coloring \nplatform was used. \nExpression estimation system \nA semi-quantitative method was used to assess the im -\nmunohistochemical expression: 1%–10%=1; 10%–50%=2; \n>50%=3. \nIntensity of immunohistochemical expression: 0=miss -\ning; 1(+)=weak; 2(+)=moderate; 3(+)=strong. \nWe reported diffuse, focal, and heterogeneous expres -\nsion patterns. \nStatistical analysis \nDescriptive and inferential statistics were performed. The \nnon-normally distributed data were expressed as median and \npercentiles (25th; 75th). Comparisons between more than two \nindependent groups were carried out using the nonparamet-\nric Kruskal-Wallis test (H). Multiple-comparison post hoc \ntest was used if significant differences were found. Categori-\ncal variables were presented as absolute/relative frequencies \n(counts/%) and z-test was applied to test for difference of rel-\native parts/shares between the groups. Statistical analysis of \nthe data was performed using SPSS v. 26 for Windows (IBM \nCorp. Released 2019. Armonk, NY: IBM Corp). For all tests, \np-value ˂0.05 indicated statistical significance. \nRESULTS \nA retrospective analysis was conducted on a total of 296 \ncases from 2019 to 2023. Among these cases, a subset of 50 \n\nExpression of HIF-1α, Ki67, SMA, and E-Cadherin\n99\nFolia Medica I 2024 I Vol. 66 I No. 1\nwas chosen for immunohistochemistry testing. The present \nstudy examined a cohort of women, whose median age was \n64.5 years (54; 71 years), who were categorized into three \ndistinct groups: 16 individuals (32.0%) diagnosed with en-\ndometriosis, 17 individuals (34.0%) diagnosed with endo -\nmetrial carcinoma, and 17 individuals (34.0%) diagnosed \nwith ovarian carcinoma. A distribution was generated to \nrepresent the number and proportion of patients in the three \ngroups within the designated time frame. A statistically sig-\nnificant difference was seen in the age distribution of the pa-\ntients under examination across different groups (H=16.44, \np=0.000). Following a post hoc analysis, it was seen that \npatients diagnosed with endometriosis with a median age \nof 51 years exhibited a statistically significant difference in \nage when compared to patients diagnosed with endometrial \ncancer, who had a median age of 68 years ( p=0.002). Fur-\nthermore, patients with endometriosis were also shown to be \nstatistically substantially younger than those diagnosed with \novarian carcinoma, with a median age of 71 years (p=0.001). \nThere was no difference between the median ages of individ-\nuals diagnosed with endometrial and ovarian carcinomas. \nThe proportion of the heterogeneous E-cadherin stain -\ning pattern in ovarian cancer (52.9%) was statistically sig -\nnificantly higher compared to the other two groups, name-\nly endometriosis focus (6.3%) and endometrial carcinoma \n(11.8%) (z-test, p<0.05). Additionally, the prevalence of \ndiffuse staining E-cadherin pattern was found to be sub -\nstantially greater in cases of endometriosis (93.8%) and \nendometrial carcinoma (88.2%) as compared to ovarian \ncarcinoma (47.1%) (z-test, p<0.05). \nThe results are shown in Table 1 and Fig. 1A. \nIn cases with reduced expression of E-cadherin, we re -\nported a positive EMT status, in case of preserved expres -\nTable 1. Relative proportions of E-cadherin expression categories by staining pattern by group \nN Endometriosis Endometrial cancer Ovarian cancer\nHeterogeneous pattern 1 (6.3%) 2 (11.8%) 9 (52.9%)\nDiffuse pattern 15 (93.8%) 15 (88.2%) 8 (47.1%)\nTotal 16 (100%) 17 (100%) 17 (100%)\nsion – a negative EMT status. \nThe proportion of negative epithelial-mesenchymal \ntransition (EMT) in endometriosis (87.5%) was shown to \nstatistically significantly higher compared to ovarian can -\ncer (23.5%) (z-test, p<0.05). Furthermore, the statistical \nanalysis revealed a statistically significantly higher occur -\nrence of positive epithelial-mesenchymal transition (EMT) \nin ovarian cancer (76.5%) compared to endometriosis \n(12.5%) (z-test, p<0.05) (Table 2). \nHIF-1α, which serves as the principal functional pro -\ntein within the HIF-1 complex, had a high level of HIF-1α \nexpression in instances of endometrial carcinoma cases, at \nthe invasive tumor front, and in proximity to areas exhibit-\ning necrotic tissue. \nIn cases involving endometriosis, there was a notable \nincrease in HIF-1α expression within adenomyosis and en-\ndometriosis foci as compared to the expression detected in \nnormal endometrium, as shown in Fig. 1B. \nWe observed increased expression at the tumor-invasive \nfront. HIF-1α expression was found to be associated with \ntumor grade, indicating a progressive increase in strength. \nA statistically significantly higher proportion of HIF-\n1α positive cells between 25% and 50% was found in en -\ndometrial carcinoma (58.8%) compared to ovarian carci -\nnoma (11.8%) (z-test, p<0.05) (Fig 1C, D). In cases with \nhigh HIF-1α expression (more than 75%) is observed sta -\ntistically significant difference between ovarian carcino -\nma (41.2%) compared to endometrial carcinoma (5.9%) \n(z-test, p<0.05). \nThe relative share of the diffuse pattern of staining for \nHIF-1α in endometriotic focus (62.5%) compared to en -\ndometrial carcinoma was statistically significantly higher \n(11.8%) (z-test, p<0.05) (Table 3). \nTable 2. Relative proportions of the categories of E-cadherin expression along the epithelial-mesenchymal transition in the three \nstudied groups \nN Endometriosis Endometrial cancer Ovarian cancer\nNegative EMT status (preserved expression of E-cadherin) 14 (87.5%) 10 (58.8%) 4 (23.5%)\nPositive EMT status (reduced to missing E-cadherin expression) 2 (12.5%) 7 (41.2%) 13 (76.5%)\nTotal 16 (100%) 17 (100%) 17 (100%)\nTable 3. Relative proportions of anti HIF-1α expression categories according to the staining pattern by group \nN Endometriosis Endometrial cancer Ovarian cancer\nPerinecrotic 0 (0.0%) 4 (23.5%) 4 (23.5%)\nDiffuse 10 (62.5%) 2 (11.8%) 6 (35.3%)\nMixed 3 (18.8%) 2 (11.8%) 4 (23.5%)\nHeterogeneous 3 (18.8%) 9 (52.9%) 3 (17.6%)\nTotal 16 (100%) 17 (100%) 17 (100%)\n\n100\nD. Markov et al.\nFolia Medica I 2024 I Vol. 66 I No. 1\nThere is a statistically significant difference in the pro -\nportion of positive Ki67 cells, ranging from 1% to 10%, in \nendometriosis focus (87.5%) compared to the two other \ngroups, endometrial carcinoma (29.4%) and ovarian can -\ncer (11.8%) (z-test, p<0.05). Moreover, there was a statis -\ntically significant increase in the proportion of Ki67-pos -\nitive cells ranging from 10% to 50% in endometrial \ncancer (58.8%) compared to endometriosis (12.5%) (z-test, \np<0.05) (Fig. 1E). In ovarian cancer, the maximum relative \npercentage of Ki67 positive cells exceeds 50% (41.2%). In \nthe other two groups, namely endometrial carcinoma and \nendometriotic focus, the relative proportions of Ki67 pos -\nitive cells are observed to be 11.8% and 0%, respectively. \nNo statistically significant difference was observed be -\ntween the relative proportions of the SMA expression cate-\ngories in the three groups (z-test, p≥0.05). A moderate type \nof expression predominated in all three groups, as did a \ndiffuse staining pattern (Fig. 1F). \nFigure 1. A. E-cadherin, IHC, diffuse expression pattern, low grade endometrial carcinoma, ×100; B. Nuclear and cytoplasmic expres-\nsion of HIF-1α in an endometriosis focus, ×100; C. Strong nuclear expression of HIF-1α in high grade endometrioid carcinoma, com-\nbined with endometriosis, strong perinecrotic expression in the tumor and weak diffuse expression in the endometriosis focus, ×40; D. \nHeterogeneous expression pattern of HIF-1α in clear cell variant ovarian carcinoma in the nucleus and cytoplasm of tumor cells, ×100; \nE. IHC expression of Ki67 - 75% proliferative index in moderately differentiated endometrial carcinoma, ×100; F. Cytoplasmic and \nmembrane expression of SMA in endometrioid variant ovarian carcinoma, ×100. \n\nExpression of HIF-1α, Ki67, SMA, and E-Cadherin\n101\nFolia Medica I 2024 I Vol. 66 I No. 1\nDISCUSSION \nHypoxia is a common change in the tumor microenviron-\nment of solid malignancies due to an imbalance between \nthe rapid growth of tumors and their blood supply. In addi-\ntion, hypoxia has been shown to induce resistance to che -\nmotherapy and radiotherapy. We show that diffuse expres-\nsion of HIF-1α predominates in cases with endometriosis \nand endometrial carcinoma, and a heterogeneous expres -\nsion pattern is also observed in ovarian carcinomas. In type \n1 endometrial carcinoma, HIF-1α expression correlates \nwith tumor grading and FIGO stage, which has also been \nreported by other authors.[6] \nIn type 2 endometrial carcinoma, stronger and diffuse \nexpression, including perinecrotic expression of HIF-1α \nwas observed in all examined patients, regardless of the \ndepth of myometrial invasion, vascular invasion, and TNM \nstage of the tumor. This dependence is well expressed in \nhigh-grade carcinomas. \nImmunohistochemical expression of HIF-1α was great -\ner in high-grade endometrial carcinomas compared with \nlow-grade carcinomas, but this difference was not statis -\ntically significant. We hypothesize that the lack of statisti -\ncal significance is due to the small number of cases in the \nsample. It is interesting that around areas with necrosis, we \nsimultaneously observed positive EMT and perinecrotic \nstrong expression of HIF-1α. Hypoxia is likely to underlie \nthe mechanisms in both processes. \nThe association between endometriosis and endometri-\noid and clear cell carcinoma of the ovary is well known. [7] \nA threefold higher risk of developing endometriosis-asso -\nciated ovarian carcinoma has been found in the presence \nof ovarian endometriosis.[8] However, the relationship be-\ntween endometriosis and endometrial carcinoma has not \nbeen well studied.[9] \nEndometriosis and endometrial carcinoma share com -\nmon etiologic factors, including estrogen stimulation and \nchronic inflammation. Atypical endometriosis is a pre -\ncursor lesion associated with malignant transformation \nand with increased the risk of endometrial carcinoma. [10] \nEndometriosis was found in 30% of cases of synchronous \nendometrioid carcinomas of the endometrium and the \novary. [11] In our study, in 11 cases of combination between \nendometriosis and endometrial carcinoma, we reported \na more advanced FIGO stage. We hypothesize that endo -\nmetriosis paves the way for tumor cells among the uterine \nmyometrium in adenomyosis. \nEndometrioid ovarian carcinoma histologically resem -\nbles the endometrium, and recent studies have shown an \nassociation of endometriosis with endometrioid, clear cell, \nand low-grade serous ovarian carcinoma[12], as well as in the \ncases described by us. Adenomyosis is a condition in which \nendometrial glands and stroma are present in the myometri-\num of the uterus.[13] In cases with endometrioid carcinoma \nand adenomyosis, we observed deep myometrial invasion. \nLoss of E-cadherin activates the Wnt-signaling path -\nway and leads to EMT. [14] E-cadherin-mediated cell ad -\nhesion is inactivated by different mechanisms in cancers. \nSuppression of the E-cadherin/β-catenin complex as well \nas upregulation of SMA are known to be key processes in \nEMT. An important aspect of EMT is the aberrant localiza-\ntion of  β-catenin expression. [15] Tumor hypoxia decreases \nE-cadherin expression, leads to EMT, and helps tumor cells \nto avoid programmed cell death and adapt to unfavorable \nconditions.[16]  \nStudies on the immunohistochemistry expression of \nE-cadherin in relation to endometriosis have yielded in -\nconsistent findings. In our study, E-cadherin expression \nin peritoneal and ovarian endometriosis cases was weaker \ncompared to the adenomyosis expression. Around areas of \nnecrosis, we observed reduced expression of E-cadherin in \ntumor cells in ovarian and endometrial cancers. \nKi67 protein is a cell proliferation marker. The number \nof Ki67-positive tumor cells often correlates with the clin -\nical course.[17] The Ki67 index is higher in advanced stage \ntumors; a higher Ki67 index indicates more aggressive tu -\nmor behavior and worse clinical outcomes. [18] The same \ntrend is observed with the proliferative index in low- and \nhigh-grade endometrial carcinomas. In Ki67 positive cases, \npositive EMT status predominated by frequency. \nAlthough we did not find a statistical relationship be -\ntween EMT status and proliferative index in each of the \nstudied groups of working material, we performed a com -\nparative analysis of the same tumor areas in cases with \nEMT positive status with a heterogeneous pattern and high \nKi67 expression (50-100%). In areas of reduced E-cadherin \nexpression, we observed increased expression with Ki67. \nAnd the inverse was valid. \nEndometriosis is not a neoplastic disease, but it involves \ncertain processes showing hallmarks of malignancy and \ncarcinogenesis.[19] There is increasing interest in the role of \nthe Ki67 monoclonal antibody in the development of en -\ndometriosis. Ki67 is a nuclear protein associated with cell \nproliferation.[20] Although little is known about the specific \nroles of Ki67, it is present in all active phases of the cell \ncycle but is absent in resting (G0) cells.[20]  \nEndometrial cell proliferation in patients with endome-\ntriosis was higher than that in patients without endome -\ntriosis, as determined by the proliferation index Ki67. [21] \nA higher level of Ki67 is associated with malignant tumors \nand metastasis.[22] Whether Ki67 is associated with endo -\nmetriosis recurrence is not yet known. HIF-1α and Ki67 \nmay be useful in identifying endometriosis patients who \nare at risk and need more specialized care.\nAn important histological feature of endometriosis \nis the presence of dense fibrous tissue in and around the  \nlesions[23], especially in deep infiltrating endometriosis \n(DIE)[24]. Fibrosis can lead to subsequent adhesions, an -\natomic deformity, and pelvic pain, and because fibrosis \nin many organs is generally difficult to treat, much less \ncure[25], fibrosis in endometriotic lesions is very likely to be \nresponsible for resistance to therapy, especially in DIE[25]. \nAnother feature of endometriosis is the universal pres -\nence of smooth muscle in or around endometriotic lesions, \n\n102\nD. Markov et al.\nFolia Medica I 2024 I Vol. 66 I No. 1\noften referred to as smooth muscle metaplasia (SMM). \nSMM is common in peritoneal [26], deep [27], ovarian [28]  \nendometriosis, as well as in adenomyosis [29]. The most \npronounced fibrosis was observed in cases with peritoneal  \nendometriosis. The possibility of stromal cells differenti -\nated into smooth muscle cells (SMCs) undergoing phys -\niological SMM in the uterine connective tissue is not yet \nsufficiently evidenced.[30]  \nSome authors associate the expression of SMA in endo-\nmetriosis and endometrial carcinomas with EMT, other au-\nthors suggest that the strong expression of SMA in the stro-\nma of endometrial lesions is the result of smooth muscle \nmetaplasia of the stromal cells in the endometriotic focus. \nThe observed strong diffuse expression of SMA in endome-\ntriosis lesions support the second hypothesis. \nCONCLUSIONS \nThe immunohistochemical profile of the different mor -\nphologic lesions of the endometrium and ovaries can be \nused to analyze the progression of endometriosis in tumor \ntissue, as well as to assess the progression of ovarian and \nendometrial carcinomas. Selected immunohistochemi -\ncal markers are relevant in the assessment of proliferative \nactivity, invasion and tumor progression and may serve as \nprognostic factors and for future therapy. \nEndometriosis should be considered as a disease with \nthe potential for malignancy. Morphological and immu -\nnohistochemical evaluation of endometriotic tissue can \nincrease the clinicians’ awareness of the potential of an en-\ndometriotic lesion. Decreased expression of E-cadherin in \nendometriosis and a proliferative index greater than 10% \nare grounds for a follow-up and more of an increased dis -\nease recurrence. \nMorphologic features such as intratumoral hypoxia and \nareas of necrosis in ovarian and endometrial carcinomas are \npoor prognostic markers, as is a high proliferative index. \nAcknowledgements \nThe present study is funded by the Medical University of \nPlovdiv through doctoral project DPDP No. 04/2022. \nREFERENCES \n1. 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J Clin Med 2022; 11(2):467.\nЭкспрессия HIF-1α, Ki67, SMA и E-кадгерина  \nпри эндометриозе, раке эндометрия и яичников\nДаниел Марков 1, Елена Порязова 1, Ралица Райчева 2, Г алабин Марков 3 \n1 Кафедра общей и клинической патологии, Факультет медицины, Медицинский университет – Пловдив, Пловдив, Болгария\n2 Кафедра „Социальная медицина и общественное здравохранение“, Факультет общественного здравоохранения, Медицинский университет – \nПловдив, Пловдив, Болгария \n3 Факультет медицины, Медицинский университет – Пловдив, Пловдив, Болгария \nАдрес для корреспонденции: Даниел Марков, Кафедра общей и клинической патологии, Факультет медицины, Медицинский университет \n– Пловдив, бул. „Васил Априлов“ № 15А, 4002 Пловдив, Болгария; E-mail: daniel_mark@abv.bg\nДата получения: 14 сентября 2023  ♦ Дата приемки: 10 ноября 2023 ♦ Дата публикации: 29 февраля 2024\nОбразец цитирования:  Markov D, Poryazova E, Raycheva R, Markov G. Expression of HIF-1α, Ki67, SMA and E-cadherin in \nendometriosis, endometrial and ovarian carcinoma. Folia Med (Plovdiv) 2024;66(1):97-103. doi: 10.3897/folmed.66.e112757.\nРезюме\nВведение: Эндометриоз – доброкачественное гинекологическое заболевание, которое имеет много общих характеристик  \nс раковыми клетками, включая уклонение от иммунитета, выживаемость, адгезию, инвазию и ангиогенез. Одновременное \nисследование тканевой гипоксии, ЭМП и пролиферативного индекса при эндометриозе, карциномах эндометрия и яичников \nможет дать новое представление об эволюции и прогрессировании гинекологических новообразований.\nЦель: Целью нашего исследования было проследить иммуногистохимическую экспрессию при эндометриозе, карциноме эн -\nдометрия и яичников в связи с тканевой гипоксией и некрозом, ЭМП, пролиферативным индексом и фиброзом.\nМатериалы и методы: В настоящем исследовании использовались образцы биопсии 50 пациенток с эндометриозом, карци -\nномой эндометрия и карциномой яичников с целью поиска корреляции между экспрессией HIF-1α, Ki67, SMA и E-кадгерина \nи различными клинико-патологическими особенностями.\nРезультаты: Мы наблюдали гетерогенность и различную интенсивность иммуногистохимической экспрессии у разных групп \nпациентов. Иммуногистохимическую экспрессию сравнивали со степенью дифференцировки опухолевых клеток. Клетки \nнизкодифференцированных аденокарцином показали более высокий пролиферативный индекс Ki67, наличие эпителиаль -\nно-мезенхимального перехода со сниженной экспрессией Е-кадгерина при более сильной экспрессии HIF-1α. Что касается \nSMA(гладкомышечный актин) в очагах эндометриоза органов малого таза и яичников, мы сообщили о сильной диффузной \nэкспрессии в стромальных клетках с выраженным фиброзом.\nЗаключение: Понимание механизмов канцерогенеза и прогрессирования гинекологических опухолей и эндометриоза важно \nдля прогноза, ответа на терапию и, возможно, лучшего лечения пациенток.\nКлючевые слова \nэндометриоз, карцинома эндометрия, гипоксия, иммуногистохимия, рак яичников","source_license":"CC0","license_restricted":false}