Head and Neck TumorsHead and Neck TumorsОпухоли головы и шеи2222-14682411-4634Publishing House ABV Press20010.17650/2222-1468-2016-6-1-55-67ORIGINAL REPORTОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕResults of investigating the characteristics of bone marrow in patients with squamous cell carcinoma of the head and neck, their clinical valueРезультаты исследования характеристик костного мозга больных плоскоклеточным раком головы и шеи, их клиническое значениеTimoninaE. G.ТимонинаЕ. Г.
Russian Federation
helentim@mail.ruTupitsynN. N.ТупицынН. Н.
Russian Federation
PodvyaznikovS. O.ПодвязниковС. О.
Russian Federation
SpiridonovaV. A.СпиридоноваВ. А.
Russian Federation
Frenkel’M. A.ФренкельМ. А.
Russian Federation
KolbatskayaO. P.КолбацкаяО. П.
Russian Federation
ChegrinetsO. A.ЧегринецО. А.
Russian Federation
N.N. Blokhin Russian Cancer Research Center at the Ministry of Health of RussiaФГБУ «РОНЦ им. Н.Н. Блохина» Минздрава России23 Kashirskoe Shosse, Moscow, 115478, RussiaРоссия, 115478, Москва, Каширское шоссе, 23Russian Medical Academy of Postgraduate Education at the Ministry of Health of RussiaГБОУ ДПО «РМАПО» Минздрава России2/1 Barrikadnaya St., Moscow, 125993, RussiaРоссия, 125993, Москва, ул. Баррикадная, 2/1A.N. Belozerskiy Research Institute of Physicochemical Biology, M.V. Lomonosov Moscow State UniversityНаучно-исследовательский институт физико-химической биологии им. А.Н. Белозерского Московского государственного университета им. М.В. ЛомоносоваBuild. 40, 1 Leninskie Gory, 119992, Moscow, RussiaРоссия, 119992, Москва, Ленинские горы, 1, стр. 40300320166155673003201630032016Copyright ©; 2016, Timonina E.G., Tupitsyn N.N., Podvyaznikov S.O., Spiridonova V.A., Frenkel’ M.A., Kolbatskaya O.P., Chegrinets O.A.Copyright ©; 2016, Тимонина Е.Г., Тупицын Н.Н., Подвязников С.О., Спиридонова В.А., Френкель М.А., Колбацкая О.П., Чегринец О.А.2016Timonina E.G., Tupitsyn N.N., Podvyaznikov S.O., Spiridonova V.A., Frenkel’ M.A., Kolbatskaya O.P., Chegrinets O.A.Тимонина Е.Г., Тупицын Н.Н., Подвязников С.О., Спиридонова В.А., Френкель М.А., Колбацкая О.П., Чегринец О.А.https://creativecommons.org/licenses/by/4.0https://ogsh.abvpress.ru/jour/article/view/200

To reveal the specific features of hematopoiesis in patients with head and neck squamous cell carcinoma (HNSCC), the authors analyzed the indicators of 41 bone marrow aspirates in relation to the clinical and morphological characteristics of the tumor and micrometastases detected in bone marrow. Puncture samples were morphologically and molecularly examined at the Laboratory of Hematopoiesis Immunology, N.N. Blokhin Russian Cancer Research Center. The found changes in the bone marrow cell composition in HNSCC patients showed themselves as an increase in the relative count of segmented neutrophils and a decrease in the level of immature granulocytes with no alternations in the neutrophil maturation index and in the percentage of granulocyte lineage cells. Bone marrow hypocellularity is a characteristic feature of high-grade HNSCC. The significantly enhanced leuko-erythroblastic ratio was due to a reduction in red blood cells: the erythroid cell maturation index rose, by increasing the percentage of bone marrow oxyphilic normoblasts in patients with locally advanced HNSCC. A highly sensitive method for detecting mRNA of the specific squamous cell carcinoma protein E48 was perfected using reverse-transcription polymerase chain reaction and Southern blotting, followed by an enzyme immunoassay that could recognize bone marrow micrometastases in 35 % of the patients with HNSCC. The patients with found bone marrow micrometastases showed a significant decrease in the proportion of polychromatophilic normoblasts and a significant increase in granulocytes in the presence of normal values of lymphocytes and other cellular elements of myelograms. It was established that in the presence of regional lymph node involvement, bone marrow micrometastases were significantly more frequently in the patients with HNSCC and tumor progression over a period of up to 9 months. 

bone marrowmicrometastaseshead and neck squamous cell carcinomahematopoiesisreverse-transcriptase polymerase chain reactionamplified complementary DNA E48костный мозгмикрометастазыплоскоклеточный рак головы и шеигемопоэзполимеразная цепная реакция с обратной транскрипциейамплифицированная комплементарная ДНК Е481. Статистика злокачественных новообразований в России и странах СНГ в 2013 году. Под ред.: М.И. Давыдова, Е.М. Аксель. М., 2015. [Statistics of malignant neoplasms in Russia and CIS countries in 2013. By eds.: М.I. Davydov, Е.М. Аksel’. Мoscow, 2015. (In Russ.)].Статистика злокачественных новообразований в России и странах СНГ в 2013 году. Под ред.: М.И. Давыдова, Е.М. Аксель. М., 2015. [Statistics of malignant neoplasms in Russia and CIS countries in 2013. By eds.: М.I. Davydov, Е.М. Аksel’. Мoscow, 2015. (In Russ.)].2. Пачес А.И. Опухоли головы и шеи. М.: Медицина, 2000. С. 126–42; 320–40. [Paches А.I. Head and neck tumors. Мoscow: Меditsina, 2000. Pp. 126–42; 320–40. (In Russ.)].Пачес А.И. Опухоли головы и шеи. М.: Медицина, 2000. С. 126–42; 320–40. [Paches А.I. Head and neck tumors. Мoscow: Меditsina, 2000. Pp. 126–42; 320–40. (In Russ.)].3. Матякин Е.Г. Клинические аспекты регионарного метастазирования рака языка и гортани. Автореф. дис. ... д-ра мед. наук. М., 1988. [Маtyakin Е.G. Clinical aspects of the regional tongue and pharynx metastases. Author’s abstract of thesis ... of doctor of medicine. Мoscow, 1988. (In Russ.)].Матякин Е.Г. Клинические аспекты регионарного метастазирования рака языка и гортани. Автореф. дис. ... д-ра мед. наук. М., 1988. [Маtyakin Е.G. Clinical aspects of the regional tongue and pharynx metastases. Author’s abstract of thesis ... of doctor of medicine. Мoscow, 1988. (In Russ.)].4. Нуммаев Г.М. Рак гортаноглотки (современные методы диагностики, лечения и прогноза). Автореф. дис. ... д-ра мед. наук. М., 1988. [Nummaev G.М. Hypopharynx cancer (modern diagnostics, treatment and forecast method). Author’s abstract of thesis ... of doctor of medicine. Мoscow, 1988. (In Russ.)].Нуммаев Г.М. Рак гортаноглотки (современные методы диагностики, лечения и прогноза). Автореф. дис. ... д-ра мед. наук. М., 1988. [Nummaev G.М. Hypopharynx cancer (modern diagnostics, treatment and forecast method). Author’s abstract of thesis ... of doctor of medicine. Мoscow, 1988. (In Russ.)].5. Kademani D., Bell R.B., Bagheri S. et al. Prognostic factors in intraoral squamous cell carcinoma: the influence of histologic grade. J Oral Maxillofac Surg 2005;63(11): 1599–605.Kademani D., Bell R.B., Bagheri S. et al. Prognostic factors in intraoral squamous cell carcinoma: the influence of histologic grade. J Oral Maxillofac Surg 2005;63(11): 1599–605.6. Aхундов А.А. Клиническое значение диплоидности ДНК при плоскоклеточном раке слизистой оболочки полости рта. Автореф. дис. ... канд. мед. наук. М., 2000. [Akhundov А.А. Clinical value of the DNA diploidy at the epidermoid cancer of the oral mucosa. Author’s abstract of thesis ... of candidate of medicine. Мoscow, 2000. (In Russ.)].Aхундов А.А. Клиническое значение диплоидности ДНК при плоскоклеточном раке слизистой оболочки полости рта. Автореф. дис. ... канд. мед. наук. М., 2000. [Akhundov А.А. Clinical value of the DNA diploidy at the epidermoid cancer of the oral mucosa. Author’s abstract of thesis ... of candidate of medicine. Мoscow, 2000. (In Russ.)].7. Уваров А.А. Органосохраняющие методы лечения местно-распространенного рака орофарингеальной области. Дис. ... д-ра мед. наук. М., 1997. [Uvarov А.А. Оrgan-preserving methods of treatment of the local cancer of the oropharyngeal area. Thesis ... of doctor of medicine. Мoscow, 1997. (In Russ.)].Уваров А.А. Органосохраняющие методы лечения местно-распространенного рака орофарингеальной области. Дис. ... д-ра мед. наук. М., 1997. [Uvarov А.А. Оrgan-preserving methods of treatment of the local cancer of the oropharyngeal area. Thesis ... of doctor of medicine. Мoscow, 1997. (In Russ.)].8. Худират С.А. Анализ ДНК-цитометрических данных и их использование для прогнозирования течения опухолевого процесса при злокачественных опухолях слизистой оболочки полости рта и гортани. Автореф. дис. ... канд. биол. наук. М., 1998. [Khudirat S.А. Аnalysis of DNAcytometric data and its use for the forecasting of the tumor process course at malignant neoplasms of the mouth cavity and pharynx. Author’s abstract of thesis ... of candidate of biology. Мoscow, 1998. (In Russ.)].Худират С.А. Анализ ДНК-цитометрических данных и их использование для прогнозирования течения опухолевого процесса при злокачественных опухолях слизистой оболочки полости рта и гортани. Автореф. дис. ... канд. биол. наук. М., 1998. [Khudirat S.А. Аnalysis of DNAcytometric data and its use for the forecasting of the tumor process course at malignant neoplasms of the mouth cavity and pharynx. Author’s abstract of thesis ... of candidate of biology. Мoscow, 1998. (In Russ.)].9. Colnot D.R., Nieuwenhuis E.J., Kuik D.J. et al. Clinical significance of micrometastatic cells detected by E48 (Ly-6D) reverse transcription-polymerase chain reaction in bone marrow of head and neck cancer patients. Clin Cancer Res 2004;10(23): 7827–33.Colnot D.R., Nieuwenhuis E.J., Kuik D.J. et al. Clinical significance of micrometastatic cells detected by E48 (Ly-6D) reverse transcription-polymerase chain reaction in bone marrow of head and neck cancer patients. Clin Cancer Res 2004;10(23): 7827–33.10. Partridge M., Brakenhoff R., Phillips E. et al. Detection of rare disseminated tumor cells identifies head and neck cancer patients at risk of treatment failure. Clin Cancer Res 2003;9(14):5287–94.Partridge M., Brakenhoff R., Phillips E. et al. Detection of rare disseminated tumor cells identifies head and neck cancer patients at risk of treatment failure. Clin Cancer Res 2003;9(14):5287–94.11. Крохина О.В. Микрометастазы рака молочной железы в костный мозг. Иммуноморфологическая диагностика. Дис. ... канд. мед. наук. М., 2003. [Krokhina О.V. Мicrometastases of the mammary gland cancer to the bone marrow. Immunomorphologic diagnostics. Thesis ... of candidate of medicine. Мoscow, 2003. (In Russ.)].Крохина О.В. Микрометастазы рака молочной железы в костный мозг. Иммуноморфологическая диагностика. Дис. ... канд. мед. наук. М., 2003. [Krokhina О.V. Мicrometastases of the mammary gland cancer to the bone marrow. Immunomorphologic diagnostics. Thesis ... of candidate of medicine. Мoscow, 2003. (In Russ.)].12. Mansi J.L., Easton D., Berger U. et al. Bone marrow micrometastases in primary breast cancer: prognostic significance after 6 years’ follow-up. Eur J Cancer 1991;27(12):1552–5.Mansi J.L., Easton D., Berger U. et al. Bone marrow micrometastases in primary breast cancer: prognostic significance after 6 years’ follow-up. Eur J Cancer 1991;27(12):1552–5.13. Harbeck N., Untch M., Pache L., Eiermann W. Tumour cell detection in the bone marrow of breast cancer patients at primary therapy: results of a 3-year median follow-up. Br J Cancer 1994;69(3):566–71.Harbeck N., Untch M., Pache L., Eiermann W. Tumour cell detection in the bone marrow of breast cancer patients at primary therapy: results of a 3-year median follow-up. Br J Cancer 1994;69(3):566–71.14. Wiedswang G., Borgen E., Karesen R. et al. Detection of isolated tumor cells in bone marrow is an independent prognostic factor in breast cancer. J Clin Oncol 2003;21(18):3469–78.Wiedswang G., Borgen E., Karesen R. et al. Detection of isolated tumor cells in bone marrow is an independent prognostic factor in breast cancer. J Clin Oncol 2003;21(18):3469–78.15. Кузнецов Ю.В., Ковригина Е.С., Байдун Л.В. и др. Использование эритроцитарных индексов и показателей обмена железа в дифференциальной диагностике микроцитарных анемий. Гематология и трансфузиология 2000;45(6):46–8. [Kuznetsov Yu.V., Kovriginа E.S., Baydun L.V. et al. Using of erythrocyte indices and of iron exchange indices in the differential diagnostics of microcytic anemias. Gematologiya i transfuziologiya = Hematology and Transfusiology 2000;45(6):46–8. (In Russ.)].Кузнецов Ю.В., Ковригина Е.С., Байдун Л.В. и др. Использование эритроцитарных индексов и показателей обмена железа в дифференциальной диагностике микроцитарных анемий. Гематология и трансфузиология 2000;45(6):46–8. [Kuznetsov Yu.V., Kovriginа E.S., Baydun L.V. et al. Using of erythrocyte indices and of iron exchange indices in the differential diagnostics of microcytic anemias. Gematologiya i transfuziologiya = Hematology and Transfusiology 2000;45(6):46–8. (In Russ.)].16. Hofmann T., Buchner A., Hofstetter A. et al. Prognostic relevance of disseminated tumour cells in bone marrow of patients with transitional cell carcinoma. Eur J Cancer 2007;43(18):2678–84.Hofmann T., Buchner A., Hofstetter A. et al. Prognostic relevance of disseminated tumour cells in bone marrow of patients with transitional cell carcinoma. Eur J Cancer 2007;43(18):2678–84.17. Pantel K., Aignherr C., Kollerman J. et al. Immunocytochemical detection of isolated cells in bone marrow of patients with untreated stage C prostatic cancer. Eur J Cancer 1995;31A(10):1627–32.Pantel K., Aignherr C., Kollerman J. et al. Immunocytochemical detection of isolated cells in bone marrow of patients with untreated stage C prostatic cancer. Eur J Cancer 1995;31A(10):1627–32.18. Pantel K., Izbicki J., Passlick B. et al. Frequency and prognostic significance of isolated tumour cells in bone marrow of patients with non-small-cell lung cancer without overt metastases. Lancet 1996;347(9002):649–53.Pantel K., Izbicki J., Passlick B. et al. Frequency and prognostic significance of isolated tumour cells in bone marrow of patients with non-small-cell lung cancer without overt metastases. Lancet 1996;347(9002):649–53.19. Soeth E., Röder C., Juhl H. et al. The detection of disseminated tumor cells in bone marrow from colorectal-cancer patients by a cytokeratin-20-specific nested reverse-transcriptase-polymerase-chain reaction is related to the stage of disease. Int J Cancer 1996;69(4):278–82.Soeth E., Röder C., Juhl H. et al. The detection of disseminated tumor cells in bone marrow from colorectal-cancer patients by a cytokeratin-20-specific nested reverse-transcriptase-polymerase-chain reaction is related to the stage of disease. Int J Cancer 1996;69(4):278–82.20. Weitz J., Kienle P., Magener A. et al. Detection of disseminated colorectal cancer cells in lymph nodes, blood and bone marrow. Clin Cancer Res 1999;5(7):1830–6.Weitz J., Kienle P., Magener A. et al. Detection of disseminated colorectal cancer cells in lymph nodes, blood and bone marrow. Clin Cancer Res 1999;5(7):1830–6.21. Brakenhoff R.H., Stroomer J.G., ten Brink C. et al. Sensitive detection of squamous cells in bone marrow and blood of head and neck cancer patients by E48 reverse transcriptase-polymerase chain reaction. Clin Cancer Res 1999;5(4):725–32.Brakenhoff R.H., Stroomer J.G., ten Brink C. et al. Sensitive detection of squamous cells in bone marrow and blood of head and neck cancer patients by E48 reverse transcriptase-polymerase chain reaction. Clin Cancer Res 1999;5(4):725–32.22. Соколов В.В., Грибова И.А. Гематологические показатели здорового человека. М.: Медицина, 1972. [Sokolov V.V., Gribova I.А. Hematologic indices of healthy humans. Мoscow: Meditsina, 1972. (In Russ.)].Соколов В.В., Грибова И.А. Гематологические показатели здорового человека. М.: Медицина, 1972. [Sokolov V.V., Gribova I.А. Hematologic indices of healthy humans. Мoscow: Meditsina, 1972. (In Russ.)].23. Наследов А.Д. SPSS. Компьютерный анализ данных в психологии и социальных науках. СПб.: Питер, 2005. [Nasledov А.D. SPSS. Computer analysis of data in psychology and social sciences. Saint Petersburg: Piter, 2005. (In Russ.)]Наследов А.Д. SPSS. Компьютерный анализ данных в психологии и социальных науках. СПб.: Питер, 2005. [Nasledov А.D. SPSS. Computer analysis of data in psychology and social sciences. Saint Petersburg: Piter, 2005. (In Russ.)]24. Реброва О.Ю. Статистический анализ медицинских данных. Применение пакета прикладных программ STATISTICA. М., 2006. [Rebrovа О.Yu. Statistic analysis of medical data. Application of the applied programs’ package STATISTICA. Мoscow, 2006. (In Russ.)].Реброва О.Ю. Статистический анализ медицинских данных. Применение пакета прикладных программ STATISTICA. М., 2006. [Rebrovа О.Yu. Statistic analysis of medical data. Application of the applied programs’ package STATISTICA. Мoscow, 2006. (In Russ.)].25. Dakhama A., Hegele R.G. A nonradioactive method for rapid and sensitive detection of polymerase chain reaction products by use of bromo-desoxyuridine. Mod Pathol 1996;9(8):849–53.Dakhama A., Hegele R.G. A nonradioactive method for rapid and sensitive detection of polymerase chain reaction products by use of bromo-desoxyuridine. Mod Pathol 1996;9(8):849–53.