Russian Journal of OncologyRussian Journal of OncologyРоссийский онкологический журнал1028-99842412-9119Eco-Vector4036610.18821/1028-9984-2017-22-4-188-193ArticlesСтатьиResearch ArticleMOLECULAR TYPES IN THE PROGNOSIS OF PAPILLARY THYROID CANCER BASED ON THE ANALYSIS OF THE STATUS OF BRAF V600E, INDEX AND KI-67 EXPRESSIONМОЛЕКУЛЯРНЫЕ ТИПЫ В ПРОГНОЗЕ ПАПИЛЛЯРНОГО РАКА ЩИТОВИДНОЙ ЖЕЛЕЗЫ НА ОСНОВЕ АНАЛИЗА СТАТУСА BRAF V600E И ИНДЕКСА ЭКСПРЕССИИ KI-67IvanovAnatoly A.ИвановАнатолий Акимович

MD, Researcher of the Laboratory of Investigations of Molecular Genetic Characteristics of Tumors of the Altai Branch of the N.N. Blokhin Russian Cancer Research Center; Barnaul, 656049, Russian Federation

науч. сотр. лаборатории исследований молекулярно-генетических характеристик опухолей; 656049, г. Барнаул, ул. Никитина, д. 77

Anatolij0199@yandex.ruAvdalyanA. MАвдалянА. МGerval'dV. JГервальдВ. ЯLushnikovaE. LЛушниковаЕ. ЛZorkinaYu. NЗоркинаЮ. НKruglovaN. MКругловаН. МLazarevA. FЛазаревА. ФAltai Branch of the N.N. Blokhin Russian Cancer Research CenterАлтайский филиал ФГБУ «Российский онкологический научный центр имени Н.Н. Блохина» Минздрава РоссииInstitute of Molecular Pathology and PathomorphologyФГБНУ «Институт молекулярной патологии и патоморфологии»Altai Krai Oncology CentreКГБУЗ «Алтайский краевой онкологический диспансер»15082017224VOL 22, NO4 (2017)ТОМ 22, №4 (2017)18819322072020Copyright ©; 2017, Eco-VectorCopyright ©; 2017, ООО "Эко-Вектор"2017Eco-VectorООО "Эко-Вектор"https://rjonco.com/1028-9984/article/view/40366

The aim of our research was to determine the possibilities to stratify patients with papillary thyroid cancer (PTC) on the group’s forecast, depending on the status of the mutation BRAF v600e and Ki-67 expression. The study included 89 PTC patients with the known prognosis for the period of 2005-2015. They were treated in the Altai regional oncology center and underwent surgery for PTC over the period of 2005-2013. Mutation p. Val600Glu (V600E) BRAF gene was determined with the use of allele-specific real-time PCR kit «Real-time-PCR-BRAF-V600E («BioLink»)». Immunohistochemical examination was performed with antibodies Ki-67 (clone MIB1, «DAKO») on stainer «Ventana XT» according to standard protocols. We revealed BRAF V600E not to be an independent predictor. Different variants of PTC, depending on the level of expression of Ki-67 in combination with a mutation of BRAF V600E was allowed to identify 3 groups of molecular types of PTC: a lack of mutation and a low Ki-67 (type I), with mutation and a low Ki-67 (type II) and with the presence and/or absence of a mutation and high level Ki-67 (type III). I molecular type PTC is the most favorable from the point of view of survival: 100% of patients live 10 years. Molecular type II is characterized by an intermediate prognosis: 76% of patients lived out up to 10 years. Molecular type III is characterized by the poor prognosis: only 36.8 percent of cases lived up to 10 years. In multivariate analysis of survival in PTC patients the independent prognostic factor happened to be the molecular type of tumor. In this case χ2 = 35 at p ≤ 0.000005.

Цель нашей работы - определение возможности стратификации пациентов с папиллярным раком щитовидной железы (ПРЩЖ) на группы прогноза в зависимости от статуса мутации BRAF V600E и индекса Ki-67. В исследование вошли 89 пациентов с ПРЩЖ, прогноз которых известен за период 2005-2015 гг., пролеченных в Алтайском краевом онкологическом диспансере и перенёсших операцию по поводу ПРЩЖ за период 2005-2013 гг. Мутация p. Val600Glu (V600E) гена BRAF определялась с помощью аллель-специфичной ПЦР в реальном времени набором Real-time-PCR-BRAF-V600E («Биолинк»). Иммуногистохимическое исследование проводили с антителами Ki-67 (клон MIB1, DAKO) на стейнере Ventana XT по стандартным протоколам. Мы выявили, что BRAF V600E не является независимым прогностическим критерием. Различные варианты ПРЩЖ в зависимости от уровня экспрессии Ki-67 в сочетании с мутацией BRAF V600E позволили выделить 3 группы молекулярных типов ПРЩЖ: с отсутствием мутации и низким индексом Ki-67 (I тип), с мутацией и низким индексом Ki-67 (II тип) и с наличием и/или отсутствием мутации и высоким уровнем Ki-67 (III тип). I молекулярный тип ПРЩЖ - самый благоприятный с точки зрения выживаемости: 10 лет проживает 100% больных. Молекулярный тип II характеризуется промежуточным прогнозом - 76% пациентов. Молекулярный тип III - самым неблагоприятным прогнозом - всего 36,8%. При многофакторном анализе выживаемости больных ПРЩЖ независимым фактором прогноза стал молекулярный тип опухоли. В этом случае χ2 = 35 при p ≤ 0,000005.

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