ПАТОГЕНЕЗ И МОЛЕКУЛЯРНО-ГЕНЕТИЧЕСКИЕ АСПЕКТЫ РАЗВИТИЯ ОПУХОЛЕЙ СЛЮННЫХ ЖЕЛЕЗ
Аннотация
В статье анализируются молекулярно-генетические механизмы развития опухолей слюнных желез. Рассматриваются ключевые генетические мутации (PLAG1, HMGA2, CTNNB1) и их влияние на опухолевый рост. Освещается роль дисрегуляции сигнальных путей (Wnt/β-катенин, PI3K/AKT/mTOR, NF-kB) в канцерогенезе. Особое внимание уделяется экспрессии молекулярных маркеров (CK7, p40, p63, SOX10, S-100) и их диагностическому значению. Обсуждается влияние хронического воспаления и провоспалительных цитокинов (IL-6, TNF-α) на прогрессию опухоли. Представленный обзор подчеркивает необходимость дальнейших исследований для разработки новых диагностических и терапевтических стратегий, направленных на выявление молекулярных мишеней и совершенствование подходов к лечению опухолей слюнных желез.
Об авторах
Список литературы
Santos D, Rodrigues-Fernandes ES, Speight CI, Khurram PM, Alsanie SA, Normando I, et al. Impact of tumor site on the prognosis of salivary gland neoplasms: A systematic review and meta-analysis. Critical reviews in oncology/hematology. 2021;162.
Egal ESA, Scarini JF, de Lima-Souza RA, Lavareze L, Fernandes PM, Emerick C, et al. Tumor microenvironment in salivary gland carcinomas: An orchestrated state of chaos. Oral Oncol [Internet]. 2022;127(105777):105777. Available from: http://dx.doi.org/10.1016/j.oraloncology.2022.105777
Skálová A, Hyrcza MD, Leivo I. Update from the 5th edition of the World Health Organization Classification of Head and neck tumors: Salivary glands. Head Neck Pathol [Internet]. 2022;16(1):40–53. Available from: http://dx.doi.org/10.1007/s12105-022-01420-1
Żurek M, Fus Ł, Niemczyk K, Rzepakowska A. Salivary gland pathologies: evolution in classification and association with unique genetic alterations. Eur Arch Otorhinolaryngol [Internet]. 2023;280(11):4739–50. Available from: http://dx.doi.org/10.1007/s00405-023-08110-w
Shi Z-D, Pang K, Wu Z-X, Dong Y, Hao L, Qin J-X, et al. Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies. Signal Transduct Target Ther [Internet]. 2023;8(1):113. Available from: http://dx.doi.org/10.1038/s41392-023-01383-x
Toper MH, Sarioglu S. Molecular pathology of salivary gland neoplasms: Diagnostic, prognostic, and predictive perspective: Diagnostic, prognostic, and predictive perspective. Adv Anat Pathol [Internet]. 2021;28(2):81–93. Available from: http://dx.doi.org/10.1097/PAP.0000000000000291
Naik U, Amin SE, Elsayad M, Saluja K. Pleomorphic Adenoma with a Novel Gene Rearrangement-LINC01606:: PLAG1. Head and Neck Pathology. 2024;18.
Owosho AA, Adesina OM, Odujoko O, Akinyemi H, Komolafe A, Tadros S, et al. HMGA2 Immunoexpression is frequent in salivary gland pleomorphic adenoma: immunohistochemical and molecular analyses of PLAG1 and HMGA2 in 25 cases. Int J Clin Exp Pathol. 2022;15(2):63–71.
Broseghini E, Carosi F, Berti M, Compagno S, Ghelardini A, Fermi M, et al. Salivary gland cancers in the era of molecular analysis: The role of tissue and liquid biomarkers. Cancers (Basel) [Internet]. 2025;17(4). Available from: http://dx.doi.org/10.3390/cancers17040660
Swid MA, Li L, Drahnak EM, Idom H, Quinones W. Updated salivary gland immunohistochemistry: A review. Arch Pathol Lab Med [Internet]. 2023;147(12):1383–9. Available from: http://dx.doi.org/10.5858/arpa.2022-0461-RA
Pikul J, Rzepakowska A. Molecular landscape of salivary gland malignancies. What is already known? Contemp Oncol (Pozn) [Internet]. 2024;28(3):201–16. Available from: http://dx.doi.org/10.5114/wo.2024.144288
Song P, Gao Z, Bao Y, Chen L, Huang Y, Liu Y, et al. Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy. J Hematol Oncol [Internet]. 2024;17(1):46. Available from: http://dx.doi.org/10.1186/s13045-024-01563-4
Stefani C, Miricescu D, Stanescu-Spinu I-I, Nica RI, Greabu M, Totan AR, et al. Growth factors, PI3K/AKT/mTOR and MAPK signaling pathways in colorectal cancer pathogenesis: Where are we now? Int J Mol Sci [Internet]. 2021;22(19):10260. Available from: http://dx.doi.org/10.3390/ijms221910260
Moneva-Sakelarieva M, Kobakova Y, Konstantinov S, Momekov G, Ivanova S, Atanasova V, et al. The role of the transcription factor NF-kB in the pathogenesis of inflammation and carcinogenesis. Modulation capabilities. Pharmacia. 2025;72:1–13.
He K, Gan WJ. Wnt/β-catenin signaling pathway in the development and progression of colorectal cancer. Cancer Management and Research. 2023;435–48.
Ouedraogo SY, Zoure AA, Zeye MMJ, Kiendrebeogo TI, Zhou X, Sawadogo AY, et al. BRCA1, BRCA2, TP53, PIK3CA, PTEN and AKT1 genes mutations in Burkina Faso breast cancer patients: prevalence, spectrum and novel variant. Mol Genet Genomics [Internet]. 2022;297(5):1257–68. Available from: http://dx.doi.org/10.1007/s00438-022-01914-1
Panwar V, Singh A, Bhatt M, Tonk RK, Azizov S, Raza AS, et al. Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease. Signal Transduct Target Ther [Internet]. 2023;8(1):375. Available from: http://dx.doi.org/10.1038/s41392-023-01608-z
De Mello Gomes ÁN, Oliveira KK, Marchi FA, Bettim BB, Germano JN, Gonçalves Filho J, et al. TGFβ signaling pathway in salivary gland tumors. Archives of Oral Biology. 2024;162.
Basset CA, Hajj Hussein I, Jurjus AR, Cappello F, Conway de Macario E, Macario AJL, et al. The chaperone Hsp90, a key player in salivary gland tumorigenesis. Applied Biosciences [Internet]. 2023;2(4):607–16. Available from: http://dx.doi.org/10.3390/applbiosci2040038
Nonaka T, Takei H. Immunohistochemical profile of polymorphous adenocarcinoma of minor salivary gland: A systematic review and meta-analysis. Head Neck Pathol [Internet]. 2022;16(4):980–90. Available from: http://dx.doi.org/10.1007/s12105-022-01453-6
Ruddle NH. Regulation, maintenance, and remodeling of high endothelial venules in homeostasis, inflammation, and cancer. Current Opinion in Physiology. 2023;36.
Sivakumar N, Narwal A, Pandiar D, Devi A, Anand R, Bansal D, et al. Diagnostic utility of p63/p40 in the histologic differentiation of salivary gland tumors: a systematic review. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology. 2022;133:189–98.
Steurer S, Riemann C, Büscheck F, Luebke AM, Kluth M, Hube-Magg C, et al. P63 expression in human tumors and normal tissues: A tissue microarray study on 10,200 tumors. Biomark Res [Internet]. 2021;9(1):7. Available from: http://dx.doi.org/10.1186/s40364-021-00260-5
Gonzalez MF, Husain BH. Solitary fibrous tumour of the submandibular gland: Novel insights from clinical practice on a close mimicker of pleomorphic adenoma and a diagnostic challenge for the cytopathologist. Cytopathology [Internet]. 2021;32(2):261–5. Available from: http://dx.doi.org/10.1111/cyt.1293
Naso JR, Roden AC. Recent developments in the pathology of primary pulmonary salivary gland-type tumours. Histopathology. 2024;84(1):102–23.
Thompson LD. Immunohistology of Head and Neck. Diagnostic Immunohistochemistry E-Book: Diagnostic Immunohistochemistry E-Book. 2021;254.
Ismerim AB, de Oliveira Araújo IB, de Aquino Xavier FC, Rocha CAG, Macedo CL, Cangussu MCT, et al. Mast cells and proteins related to myofibroblast differentiation (PAR-2, IL-6, and TGFβ1) in salivary cancers: A preliminary study: A preliminary study. Appl Immunohistochem Mol Morphol [Internet]. 2021;29(7):e57–67.
Available from: http://dx.doi.org/10.1097/PAI.0000000000000924
Barrera MJ. Tofacitinib counteracts IL-6 overexpression induced by deficient autophagy: implications in Sjögren’s syndrome //Rheumatology. - 2021. - Т. 60. :1951–62.
Brierly G, Celentano A, Breik O, Moslemivayeghan E, Patini R, McCullough M, et al. Tumour necrosis factor alpha (TNF-α) and oral squamous cell carcinoma. Cancers (Basel) [Internet]. 2023;15(6). Available from: http://dx.doi.org/10.3390/cancers15061841
Chadwick JW, Macdonald R, Ali AA, Glogauer M, Magalhaes MA. TNFα signaling is increased in progressing oral potentially malignant disorders and regulates malignant transformation in an oral carcinogenesis model. Front Oncol [Internet]. 2021;11:741013. Available from: http://dx.doi.org/10.3389/fonc.2021.741013
Как цитировать
Это произведение доступно по лицензии Creative Commons «Attribution-NonCommercial-NoDerivatives» («Атрибуция — Некоммерческое использование — Без производных произведений») 4.0 Всемирная.