mvjrМедицинский вестник Юга РоссииMedical Herald of the South of Russia2219-80752618-7876The Rostov State Medical University10.21886/2219-8075-2018-9-3-50-57mvjr-715Research ArticleОБЗОРЫREVIEWМолекулярно-генетический профиль плоскоклеточного рака головы и шеиMolecular and genetic profile of head and neck squamous cell carcinomaСтуканьА. И.StukanA. I.

Анастасия Игоревна Стукань, аспирант кафедры онкологии, ГБУЗ «Клинический онкологический диспансер № 1» Минздрава Краснодарского края, Россия, 350040 Краснодар, ул. Димитрова, 146; кафедра онкологии с курсом торакальной хирургии факультета повышения квалификации и рофессиональной переподготовки специалистов ГБОУ ВПО «Кубанский государственный медицинский университет» Минздрава России, Россия, 350029 Краснодар, ул. Российская, 140.

Anastasiya I. Stukan, Department of Oncology with Course of Thoracic Surgery of Kuban State Medical University Ministry of Healthcare of Russia Ministry of Healthcare of Russia, 140, Rossiyskaya str., Krasnodar, 350029, Russia; SBEH «Clinical Dispensary of Oncology of Ministry of health care of Krasnodar region, 146, Dimitrova str., Krasnodar, 312510, Russia.

jolie86@bk.ruПорхановВ. А.PorhanovV. A.

Владимир Алексеевич Порханов, заведующий кафедрой онкологии с курсом торакальной хирургии факультета повышения квалификации и профессиональной переподготовки специалистов ГБОУ ВПО «Кубанский государственный медицинский университет» Минздрава России; Россия, 350029 Краснодар, ул. Российская, 140.

Vladimir A. Porhanov, Department of Oncology with Course of Thoracic Surgery of Kuban State Medical University Ministry of Healthcare of Russia Ministry of Healthcare of Russia,140, Rossiyskaya str., Krasnodar, 350029, Russia; SBEH «Scientific Investigational Institute State Clinical Hospital #1 named by professor S.V. Ochapovsky» Ministry of Healthcare of Russia, 167, 1 May str., Krasnodar,350086, Russia.

vadimbodnya@rambler.ruБодняВ. Н.BodnyaV. N.

Вадим Николаевич Бодня, доцент кафедры онкологии с курсом торакальной хирургии факультета повышения квалификации и профессиональной переподготовки специалистов ГБОУ ВПО «Кубанский государственный медицинский университет» Минздрава России; Россия, 350029 Краснодар, ул. Российская, 140; ГБУЗ «Научно-исследовательский институт – Краевая клиническая боль-ница №1 им. профессора С.В. Очаповского» Минздрава Краснодарского края; Россия, 350086, Краснодар, ул. 1 Мая, д. 167.

Vadim N. Bodnya, Department of Oncology with Course of Thoracic Surgery of Kuban State Medical University Ministry of Healthcare of Russia Ministry of Healthcare of Russia, 140, Rossiyskaya str., Krasnodar, 350029, Russia; SBEH «Scientific Investigational Institute State Clinical Hospital #1 named by professor S.V. Ochapovsky» Ministry of Healthcare of Russia, 167, 1 May str., Krasnodar,350086, Russia.

vadimbodnya@rambler.ruЧухрайО. Ю.ChuhrajO. Yu.

Ольга Юрьевна Чухрай, ГБУЗ «Клинический онкологический диспансер № 1» Минздрава Краснодарского края; Россия, 350040 Краснодар, ул. Димитрова, 146.

Olga Yu. Chuhraj, SBEH «Clinical Dispensary of Oncology of Ministry of health care of Krasnodar region, 146, Dimitrova str., Krasnodar, 312510, Russia.

lecabel@rambler.ruМакароваЮ. М.MakarovaY. M.

Юлия Михайловна Макарова, ГБУЗ «Клинический онкологический диспансер № 1» Минздрава Краснодарского края; Россия, 350040 Краснодар, ул. Димитрова, 146.

Yuliya M. Makarova, SBEH «Clinical Dispensary of Oncology of Ministry of health care of Krasnodar region, 146, Dimitrova str., Krasnodar, 312510, Russia.

bestmakarova@mail.ruЭлизбарянИ. С.ElizbaryanI. S.

Игорь Семенович Элизбарян, ГБОУ ВПО «Кубанский государственный медицинский университет» Минздрава России; Россия, 350029 Краснодар, ул. Российская, 140.

Igor S. Ehlizbaryan, FGBEU of HE Kuban State Medical University Ministry of Healthcare of Russia, 4, Sedina str., Krasnodar, 350063, Russia.

ise95@mail.ruКлинический онкологический диспансер № 1, Краснодар; Кубанский государственный медицинский университет, КраснодарРоссияClinical Dispensary of Oncology of Ministry of health care of Krasnodar region, Krasnodar; Kuban State Medical University, KrasnodarRussian FederationКубанский государственный медицинский университет, Краснодар; Научно-исследовательский институт – Краевая клиническая больница № 1 им. профессора С.В. Очаповского», КраснодарРоссияKuban State Medical University, Krasnodar; Scientific Investigational Institute State Clinical Hospital №1 n.a. prof. S.V. Ochapovsky, KrasnodarRussian FederationКлинический онкологический диспансер № 1, КраснодарРоссияClinical Dispensary of Oncology of Ministry of health care of Krasnodar region, KrasnodarRussian FederationКубанский государственный медицинский университет, КраснодарРоссияKuban State Medical University, KrasnodarRussian Federation201801102018935057Copyright © Стукань А.И., Порханов В.А., Бодня В.Н., Чухрай О.Ю., Макарова Ю.М., Элизбарян И.С., 20182018Стукань А.И., Порханов В.А., Бодня В.Н., Чухрай О.Ю., Макарова Ю.М., Элизбарян И.С.Stukan A.I., Porhanov V.A., Bodnya V.N., Chuhraj O.Y., Makarova Y.M., Elizbaryan I.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medicalherald.ru/jour/article/view/715

Все больше исследований проводится с целью выявления молекулярных путей канцерогенеза при плоскоклеточном раке головы и шеи (ПРГШ). Обсуждаются новые модели терапии ПРГШ с учетом генетических и биохимических особенностей и акцентом на значимые научные разработки. Разделение ПРГШ на две большие группы в зависимости от ассоциации с вирусом папилломы человека (ВПЧ) с различными показателями выживаемости является значимым достижением последних десятилетий в исследовании канцерогенеза и лечении рака головы и шеи. Известно, что ВПЧ-негативные опухоли возникают при воздействии химических канцерогенов. Патогенез ВПЧ-позитивного ПРГШ связан с воздействием вирусных белков ВПЧ E6 и E7. Серьёзный интерес вызывают результаты полноэкзомного секвенирования этих опухолей. Паттерн экспрессии молекулярного профиля, характеризующего пути Rb-E2F/p53 различались при ВПЧ-позитивных и ВПЧ-негативных опухолях. При анализе уровня фосфорилированных белков pRb и p16 образцов ПРГШ ВПЧ-позитивные опухоли имели меньшие уровни протеина pRb и высокий уровень p16, в отличие от ВПЧ-негативных образцов ввиду возможности белка ВПЧ E7 вызывать повреждение Rb. Экспрессия р16 была выше в ВПЧ-позитивных опухолях, что является подтверждение ВПЧ-позитивного статуса опухоли при иммуно-гистохимическом анализе. Также установлен уровень экспрессии белка p53 с целью уточнения механизма деградации в ВПЧ-позитивных опухолях. В связи с тем, что ВПЧ проявляет канцерогенные свойства путем инактивации регуляторов клеточного цикла р53 и pRb, используя экспрессию онкопротеинов E6 и E7, мутации р53 не должны играть ведущую роль в ВПЧ-индуцированном туморогенезе. Тем не менее, в отношении ВПЧ-позитивных опухолей ПРГШ имеются противоречивые данные, указывающие на наличие интегрированной ДНК онкогенного штамма, и часть этих опухолей имеет мутации р53.Также экспрессия р53 в ВПЧ-позитивных образцах соответствовала среднему значению экспрессии в ВПЧ-негативных опухолях.

To determine the molecular pathways of head and neck squamous cell carcinoma (HNSCC) tumorogenesis there are held a great amount of investigations. New therapeutic models for HNSCC are discussed considering genetic and biochemical specifications and taking in account significant scientific strategies. Dividing HNSCC into 2 large groups in accordance to human papilloma virus (HPV) association with different survival rates is a great achievement of the last decades in carcinogenesis researching and treatment of HNSCC. It is well known that chemical carcinogens are the main cause of HPV-negative tumors development. HPV-positive HNSCC is associated with E6 and E7 HPV proteins. The results of whole exome sequencing of HNSCC are of the great interest. Molecular expression profile of Rb-E2F/p53 were diff erent in HPV-positive and HPV-negative tumors. The phosphorylated pRb and p16 proteins analysis showed low pRb and high p16 levels in HPV-positive tumors in contrast to HPV-negative samples due to the HPV E7 ability to degrade Rb. P16 expression was higher in HPV-positive tumors, so it is immunohystochemical marker of HPV-positive status. The p53 expression pattern is determined also to identify its mechanism of degradation in HPV-positive tumors. Due to carcinogenic HPV ability by inactivation of cell cycle regulators р53 and pRb with the help of E6 and E7 oncoproteins, mutations of TP 53 shouldn’t play leading role in HPV-induced tomorogenity. Nevertheless, there are controversial data concerning HPV-positive tumors that part of them gain p53-mutations at the same time having integrated HPV-genome. The p53 expression in HPV-positive samples was the same as if in the absence of HPV.

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The authors declare that there are no conflicts of interest present.