Head and Neck TumorsHead and Neck TumorsОпухоли головы и шеи2222-14682411-4634Publishing House ABV Press102010.17650/2222-1468-2024-14-4-10-23DIAGNOSIS AND TREATMENT OF HEAD AND NECK TUMORSДИАГНОСТИКА И ЛЕЧЕНИЕ ОПУХОЛЕЙ ГОЛОВЫ И ШЕИMolecular profile of salivary gland tumors: discovering new targets for therapyМолекулярно-генетический портрет рака слюнных желез: поиск новых мишеней для таргетной терапииhttps://orcid.org/0000-0002-6796-0968IgnatovaA. V.ИгнатоваА. В.
Russian Federation

Anastasia Valeryevna Ignatova

24 Kashirskoe Shosse, Moscow 115522

6 Miklukho-Maklaya St., Moscow 117198

Анастасия Валерьевна Игнатова

115522 Москва, Каширское шоссе, 24

117198 Москва, ул. Миклухо-Маклая, 6

annasurge@gmail.comhttps://orcid.org/0000-0002-6851-9867AlymovYu.  V.АлымовЮ. В.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-5421-5985RomanovI.  S.РомановИ. С.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

1 Ostrovityanova St., Moscow 117513

115522 Москва, Каширское шоссе, 24

117513 Москва, ул. Островитянова, 1

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава РоссииPeoples’ Friendship University of RussiaФГАОУ ВО «Российский университет дружбы народов»N.I. Pirogov Russian National Research Medical University, Ministry of Health of RussiaФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России2712202414410231501202515012025Copyright ©; 2024, Ignatova A.V., Alymov Y.V., Romanov I.S.Copyright ©; 2024, Игнатова А.В., Алымов Ю.В., Романов И.С.2024Ignatova A.V., Alymov Y.V., Romanov I.S.Игнатова А.В., Алымов Ю.В., Романов И.С.https://creativecommons.org/licenses/by/4.0https://ogsh.abvpress.ru/jour/article/view/1020

Introduction. Due to variety of morphological subtypes and poor clinical response, comprehensive molecular profiling for salivary gland cancers become a part of treatment strategy for chemotherapy-resistant cases. Tumors of the salivary glands include more than 20 histological types distinguished by their biological characteristics, response to therapy, and prognosis. The search for specific therapeutically significant markers and mutations for various histological types of salivary gland tumors may allow the development of a diagnostic algorithm and improve patient treatment results.

Aim. To search for therapeutically significant molecular and genetic targets and immunohistochemical markers in various histological types of malignant salivary gland tumors.

Materials and methods. We analyzed data on 280 patients with unresectable recurrent and metastatic salivary gland cancer to identify the main characteristic therapeutically significant immunohistochemical (androgen receptor (AR), epidermal growth factor receptor type 2 (HER2neu), epidermal growth factor receptor (EgfR), programmed cell death receptor 1 (pD-L1) (CpS), сD117, estrogen receptor (ER), progesterone receptor (pR), pan-TRk) and molecular genetic targets (ALK, BRAF, ERBB2, KIT, MET, RET, ROS1, SMO, AR, HRAS, PIK3CA, PDGFRA, NTRK1-3) depending on the histological subtype of the tumor.

Results. Based on the results obtained, in comparison with previous studies, a greater diversity of therapeutically significant mutations, fusions and immunohistochemical markers was revealed for various histological types of tumors. Interestingly, increased expression of AR was detected not only in salivary duct carcinoma, but also in carcinoma ex pleomorphic adenoma, adenocarcinoma not otherwise specified, myoepithelial, mucoepidermoid, adenoid cystic, acinic cell, polymorphous adenocarcinomas. ETV6-NTRK3 gene fusions in addition to secretory carcinoma were detected in mucoepidermoid and salivary duct carcinomas. mutations and fusions in the RET gene have been identified in ductal and mucoepidermoid carcinomas, as well as adenocarcinoma not otherwise specified.

Conclusion. The results of the study allow to expand the group of patients for molecular genetic and IHC testing in order to individualize therapy.

Введение. с учетом разнообразия морфологических подтипов и слабого клинического эффекта стандартной терапии комплексное геномное профилирование рака слюнных желез становится частью стратегии лечения пациентов с резистентностью к химиотерапии. Опухоли слюнных желез насчитывают более 20 гистологических типов, различающихся биологическими характеристиками, ответом на терапию и прогнозом. поиск специфических терапевтически значимых маркеров и мутаций для различных гистологических типов опухолей слюнных желез позволит разработать диагностический алгоритм и улучшить результаты лечения.

Цель исследования – поиск терапевтически значимых молекулярно-генетических мишеней и иммуногистохимических маркеров при различных гистологических типах злокачественных новообразований слюнных желез.

Материалы и методы. В работе проанализированы данные 280 пациентов с нерезектабельным рецидивным и метастатическим раком слюнных желез с целью определения основных характерных терапевтически значимых  Игх-маркеров (экспрессия рецепторов андрогена (AR), эпидермального фактора роста 2-го типа (HER2), эпидермального фактора роста (EgfR), программируемой клеточной гибели 1 (pD-L1) (combined positive score (CpS) – отношение количества клеток с экспрессией pD-L1 в опухоли, лимфоцитах, макрофагах к общему количеству опухолевых клеток, умноженное на 100), сD117, эстрогена (ER), прогестерона (pR), pan-TRk) и молекулярно-генетических мишеней (альтерации генов ALK, BRAF, ERBB2, KIT, MET, RET, ROS1, SMO, AR, HRAS, PIK3CA, PDGFRA, NTRK1-3) в зависимости от гистологического типа опухоли.

Результаты. На основании полученных данных по сравнению с результатами предыдущих исследований выявлено большее разнообразие терапевтически значимых мутаций, слияний и иммуногистохимических маркеров при различных гистологических типах опухолей. повышенная экспрессия AR обнаружена не только при протоковой карциноме, но и при карциноме в плеоморфной аденоме, аденокарциноме без дополнительных уточнений, миоэпителиальной, мукоэпидермоидной, аденокистозной, ацинарноклеточной и полиморфной аденокарциномах. слияния генов ETV6-NTRK3 помимо секреторной карциномы выявлены при мукоэпидермоидной и протоковой карциномах. Мутации и слияния в гене RET обнаружены при протоковой и мукоэпидермоидной карциномах, а также при аденокарциноме без дополнительных уточнений.

Заключение. Результаты проведенного исследования позволяют расширить группу пациентов, которым показано молекулярно-генетическое и иммуногистохимическое тестирование с целью индивидуализации терапии.

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