Tumors of female reproductive systemTumors of female reproductive systemОпухоли женской репродуктивной системы1994-40981999-8627Publishing House ABV Press42410.17650/1994-4098-2015-1-69-75GYNECOLOGY. DIAGNOSISГИНЕКОЛОГИЯ. ДИАГНОСТИКАSCREENING FOR OVARIAN CANCER: REALITY AND PROSPECTS. REVIEW OF THE LITERATUREСКРИНИНГ РАКА ЯИЧНИКОВ: РЕАЛЬНОСТЬ И ПЕРСПЕКТИВЫ. ОБЗОР ЛИТЕРАТУРЫGerfanovaE. V.ГерфановаЕ. В.
Russian Federation
evgeniyagerf@gmail.comAshrafyanL. A.АшрафянЛ. А.
Russian Federation
AntonovaI. B.АнтоноваИ. Б.
Russian Federation
AleshikovaO. I.АлешиковаО. И.
Russian Federation
IvashinaS. V.ИвашинаС. В.
Russian Federation
Russian Roentgenology and Radiology Research Center, Ministry of Health of RussiaФГБУ РНЦРР Минздрава России86 Profsoyuznaya St., Moscow, 117997, RussiaРоссия, 117 997, Москва, ул. Профсоюзная, 862904201511169753004201530042015https://ojrs.abvpress.ru/ojrs/article/view/424

A review article presents the modern methods of screening and early diagnosis of primary ovarian cancer (OC). This issue is still relevant in view of the continuing upward trend in incidence rate ratios along with a slight decrease in mortality and 5-year survival rate, as well as the lack of clear definition of the concept of pathogenesis. The diagnostic value of tumor markers and their potential, advantages and disadvantages are discussed. In light of this the need becomes evident for combination of tumor markers with radiological method of imaging, such as transvaginal sonography as the most affordable, safe and multi-reproducible method enabling to most accurately determine the nature of the process, its nosology belonging, as well as to carry out the required dynamic monitoring within a short time. More advanced imaging techniques such as computer tomography or magnetic resonance imaging proved too expensive for widespread use in view of their limited sensitivity and specificity. Attempt to assess the performance of marker screening on the base of CA-125 in groups, divided by clinical and pathogenic way of OC development also proved to be ineffective. Currently, none of the presented algorithms can meet the criteria of economic efficiency, even in the most developed countries. In view of the above, possible options to enhance their performance by developing reliable multimarker panels, the use of ultrasound color power doppler mapping, and others are considered. In addition, the feasibility and application prospects of ultrasound elastometry, mass-spectrometry, IVDMIA tests, OVA dx-test as part of screening programs are discussed. The data of recent studies on the direct comparison of diagnostic tests is given. The importance of genetic counseling for persons at high risk of cancer development process is noted. In case of mutation detection in the BRCA1, BRCA2 genes, in some countries a wide range of preventive activities is recommended: from regular «targeted» preventive examinations to the prophylactic oophorectomy and mastectomy. Increased survival rate of patients with OC is the main aim of all scientific research.

В обзорной статье представлены данные о современных методах скрининга и ранней диагностики первичного рака яичников (РЯ).

Данный вопрос остается актуальным в связи с сохраняющейся тенденцией к росту показателей заболеваемости наряду с незначительным снижением смертности и 5-летней выживаемости, а также в связи с отсутствием четкой формулировки концепции патогенеза. Обсуждаются диагностическое значение опухолевых маркеров, их потенциал, преимущества и недостатки, в связи с которыми становится очевидной необходимость в их комбинации с лучевыми методами визуализации, в частности с трансвагинальной сонографией, как наиболее доступным, безопасным и многократно воспроизводимым методом, позволяющим наиболее точно определить характер процесса, его нозологическую принадлежность, а также провести необходимый динамический мониторинг в течение короткого времени. Более совершенные методы визуализации, такие как компьютерная или магнитно-резонансная томография, оказались слишком дорогими для широкого применения с учетом их ограниченной чувствительности и специфичности. Попытка рассмотреть производительность маркерного скрининга на основе СА-125 в группах, разделенных по патогенетическим и клиническим вариантам развития РЯ, также оказалась малоэффективной. В настоящее время ни один из представленных алгоритмов не может соответствовать критериям экономической эффективности даже в самых развитых странах. Ввиду вышеска- занного рассматриваются возможные варианты повышения их производительности путем разработки надежных мультимаркерных панелей, использования ультразвукового цветового энергетического доплеровского картирования и т. д. Кроме того, обсуждаются целесообразность и перспективы применения соноэластометрии, масс-спектрометрии, IVDMIА-тестов,  OVA dx-теста в рамках скрининговых программ. Приводятся данные последних исследований, посвященных непосредственному сравнению диагностических тестов. Отмечается важная роль генетического консультирования для лиц с высоким риском развития онкологического процесса. В случае выявления мутации генов BRCA1, BRCA2 в некоторых странах рекомендуется широкий спектр профилактических мероприятий: от регулярных «прицельных» профилактических осмотров до проведения профилактических овариоэктомий и мастэктомий. Увеличение выживаемости больных РЯ является главной целью всех научных изысканий.

ovarian cancera new concept of pathogenesistumor markersradiological techniquesultrasound elastometrygenetic counsel- ingmultimarker diagnostic testsultrasound transvaginal sonographyROMAOVA1OVA dx-testрак яичниковновая концепция патогенезаопухолевые маркерыметоды лучевой диагностикисоноэластомериягенетическое консультированиемультимаркерные диагностические тестытрансвагинальная ультразвуковая сонографияROMAOVA1OVA dx-тест1. Злокачественные новообразования в России в 2013 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М., 2015. С. 12, 16, 19, 136, 143. [Malignant neoplasms in Russia in 2013 (morbidity and mortality). Ed. by A.D. Caprin, V.V. Starinskiy, G.V. Petrova. Moscow, 2015. Pp. 12, 16, 19, 136, 143. (In Russ.)].Злокачественные новообразования в России в 2013 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М., 2015. С. 12, 16, 19, 136, 143. [Malignant neoplasms in Russia in 2013 (morbidity and mortality). Ed. by A.D. Caprin, V.V. Starinskiy, G.V. Petrova. Moscow, 2015. Pp. 12, 16, 19, 136, 143. (In Russ.)].2. Давыдов М.И., Аксель Е.М. Статистика злокачественных новообразований в Рос- сии и странах СНГ в 2012 г. М.: РОНЦ им. Н.Н. Блохина, 2014. С. 15, 158. [Davydov M.I., Aksel E.M. Statistics of malignancies in Russia and the CIS countries in 2012. Moscow: N.N. Blokhin RCRC, 2014. Pp. 15, 158. (In Russ.)].Давыдов М.И., Аксель Е.М. Статистика злокачественных новообразований в Рос- сии и странах СНГ в 2012 г. М.: РОНЦ им. Н.Н. Блохина, 2014. С. 15, 158. [Davydov M.I., Aksel E.M. Statistics of malignancies in Russia and the CIS countries in 2012. Moscow: N.N. Blokhin RCRC, 2014. Pp. 15, 158. (In Russ.)].3. http://globocan.iarc.fr, accessed on day/month/year.http://globocan.iarc.fr, accessed on day/month/year.4. Bray F., Ren J.S., Masuyer E., Ferlay J. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer 2013;132(5):1133–45.Bray F., Ren J.S., Masuyer E., Ferlay J. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer 2013;132(5):1133–45.5. Ferlay J., Soerjomataram I., Dikshit R. et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136(5):Е359–86.Ferlay J., Soerjomataram I., Dikshit R. et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136(5):Е359–86.6. Baker T.R., Piver M.S. Etiology, biology, and epidemiology of ovarian cancer. Semin Surg Oncol 1994;10(4):242–8.Baker T.R., Piver M.S. Etiology, biology, and epidemiology of ovarian cancer. Semin Surg Oncol 1994;10(4):242–8.7. Holschneider C.H., Berek J.S. Ovarian cancer: epidemiology, biology, and prognostic factors. Semin Surg Oncol 2000;19(1):3–10.Holschneider C.H., Berek J.S. Ovarian cancer: epidemiology, biology, and prognostic factors. Semin Surg Oncol 2000;19(1):3–10.8. Сухих Г.Т., Солодкий В.А., Ашрафян Л.А., Рожкова Н.И. Скрининг и ранняя диагно- стика гинекологического рака. М.: Молодая гвардия, 2011. С. 119–32. [Sukhikh G.T., Solodsky V.A., Ashrafyan L.A., Rozhkova N.I. Screening and early diagnosis of gynecologic cancer. Moscow: Molodaya Gvardiya, 2011. Pp. 119–32. (In Russ.)].Сухих Г.Т., Солодкий В.А., Ашрафян Л.А., Рожкова Н.И. Скрининг и ранняя диагно- стика гинекологического рака. М.: Молодая гвардия, 2011. С. 119–32. [Sukhikh G.T., Solodsky V.A., Ashrafyan L.A., Rozhkova N.I. Screening and early diagnosis of gynecologic cancer. Moscow: Molodaya Gvardiya, 2011. Pp. 119–32. (In Russ.)].9. Advances in diagnosis and management of ovarian cancer. S.A. Farghaly (ed.). N.Y., 2014. Рр. 33–58.Advances in diagnosis and management of ovarian cancer. S.A. Farghaly (ed.). N.Y., 2014. Рр. 33–58.10. Ашрафян Л.А. Спорадический рак яичников: вероятная модель патогенеза. Журнал акушерства и женских болезней 2012;61(4):3–11. [Ashrafyan L.A. Sporadic ovarian cancer: the probable modelof pathogenesis. Zhurnal akusherstva i zhenskikh bolezney = Journal of Obstetrics and Women's Diseases 2012;61(4):3–11. (In Russ.)].Ашрафян Л.А. Спорадический рак яичников: вероятная модель патогенеза. Журнал акушерства и женских болезней 2012;61(4):3–11. [Ashrafyan L.A. Sporadic ovarian cancer: the probable modelof pathogenesis. Zhurnal akusherstva i zhenskikh bolezney = Journal of Obstetrics and Women's Diseases 2012;61(4):3–11. (In Russ.)].11. Жорданиа К.И., Паяниди А.Г., Калиничева Е.В. Два пути развития сероз- ного рака яичников. Онкогинекология 2014;3:42–8. [Zhordania K.I., Payanidi A.G., Kalinicheva E.V. Two ways of development of serous ovarian cancer. Onkoginekologiya = Oncogynecology 2014;3:42–8. (In Russ.)].Жорданиа К.И., Паяниди А.Г., Калиничева Е.В. Два пути развития сероз- ного рака яичников. Онкогинекология 2014;3:42–8. [Zhordania K.I., Payanidi A.G., Kalinicheva E.V. Two ways of development of serous ovarian cancer. Onkoginekologiya = Oncogynecology 2014;3:42–8. (In Russ.)].12. Kinkel K., Hricak H., Lu Y. et al. US characterization of ovarian masses: a meta-analysis. Radiology 2000;217(3):803–11.Kinkel K., Hricak H., Lu Y. et al. US characterization of ovarian masses: a meta-analysis. Radiology 2000;217(3):803–11.13. Fishman D.A., Cohen L., Blank S.V. et al. The role of ultrasound evaluation in the detection of early-stage epithelial ovarian cancer. Am J Obstet Gynecol 2005;192(4): 1214–21.Fishman D.A., Cohen L., Blank S.V. et al. The role of ultrasound evaluation in the detection of early-stage epithelial ovarian cancer. Am J Obstet Gynecol 2005;192(4): 1214–21.14. Committee on Gynecologic Practice. The American College of Obstetricians and Gynecologists Women’s Health Care Physicians Committee Opinion № 477. March 2011 (Replaces No. 280, December 2002).Committee on Gynecologic Practice. The American College of Obstetricians and Gynecologists Women’s Health Care Physicians Committee Opinion № 477. March 2011 (Replaces No. 280, December 2002).15. https://www.sgo.org/wp-content/ uploads/2012/09/ACOG-SGO-Committee- Opinion-Role-of-OB-Gyn-2011.pdf.https://www.sgo.org/wp-content/ uploads/2012/09/ACOG-SGO-Committee- Opinion-Role-of-OB-Gyn-2011.pdf.16. Gold P., Freedman S.O. Demonstration of tumor- specific antigens in human colonic carcinomata by immunological tolerance and absorption techniques. J Exp Med 1965;121: 439–62.Gold P., Freedman S.O. Demonstration of tumor- specific antigens in human colonic carcinomata by immunological tolerance and absorption techniques. J Exp Med 1965;121: 439–62.17. Bast R.C. Jr., Feeney M., Lazarus H. et al. Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest 1981;68(5):1331–7.Bast R.C. Jr., Feeney M., Lazarus H. et al. Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest 1981;68(5):1331–7.18. Tseng P.C., Sprance H.E., Carcangiu M.L. et al. CA-125, NB/70K, and lipid-associated sialic acid in monitoring uterine papillary serous carcinoma. Obstet Gynecol 1989; 74(3 Pt 1):384–7.Tseng P.C., Sprance H.E., Carcangiu M.L. et al. CA-125, NB/70K, and lipid-associated sialic acid in monitoring uterine papillary serous carcinoma. Obstet Gynecol 1989; 74(3 Pt 1):384–7.19. Онкология: национальное руководство. Под ред. В.И. Чиссова, М.И. Давыдова. М.: ГЭОТАР-Медиа, 2008. 1072 с. [Oncology: national guidelines. Ed. by V.I. Chissov, M.I. Davydov. Moscow: GEOTAR-Media, 2008. p. 1072. (In Russ.)].Онкология: национальное руководство. Под ред. В.И. Чиссова, М.И. Давыдова. М.: ГЭОТАР-Медиа, 2008. 1072 с. [Oncology: national guidelines. Ed. by V.I. Chissov, M.I. Davydov. Moscow: GEOTAR-Media, 2008. p. 1072. (In Russ.)].20. Никогосян С.О., Кадагидзе З.Г., Шелепова В.М., Кузнецов В.В. Современ- ные методы иммунодиагностики злокаче- ственных новообразований яичников. Онко- гинекология 2014;3:49–54. [Nikoghosian S.O., Kadagidze Z.G., Shelepova V.M., Kuznetsov V.V. Modern methods of immunological diagnosis of malignant ovarian tumors. Onkoginekologiya = Oncogynecology 2014;3:49–54. (In Russ.)].Никогосян С.О., Кадагидзе З.Г., Шелепова В.М., Кузнецов В.В. Современ- ные методы иммунодиагностики злокаче- ственных новообразований яичников. Онко- гинекология 2014;3:49–54. [Nikoghosian S.O., Kadagidze Z.G., Shelepova V.M., Kuznetsov V.V. Modern methods of immunological diagnosis of malignant ovarian tumors. Onkoginekologiya = Oncogynecology 2014;3:49–54. (In Russ.)].21. Barbati A., Lauro V., Orlacchio A., Cosmi E.V. Immunoblotting characterization of CA 125 in biological fluids: difference between pregnancy and cancer CA 125 origin. Anticancer Res 1996;16(6В):3621–4.Barbati A., Lauro V., Orlacchio A., Cosmi E.V. Immunoblotting characterization of CA 125 in biological fluids: difference between pregnancy and cancer CA 125 origin. Anticancer Res 1996;16(6В):3621–4.22. Neesham D. Ovarian cancer screening. Aust Fam Physician 2007;36(3):126–8.Neesham D. Ovarian cancer screening. Aust Fam Physician 2007;36(3):126–8.23. Clarke-Pearson D.L. Clinical practice. Screening for ovarian cancer. N Engl J Med 2009;361(2):170–7.Clarke-Pearson D.L. Clinical practice. Screening for ovarian cancer. N Engl J Med 2009;361(2):170–7.24. Johnson C.C., Kessel B., Riley T.L. et al. The epidemiology of CA-125 in women without evidence of ovarian cancer in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial. Gynecol Oncol 2008;110(3):383–9.Johnson C.C., Kessel B., Riley T.L. et al. The epidemiology of CA-125 in women without evidence of ovarian cancer in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial. Gynecol Oncol 2008;110(3):383–9.25. Skates S.J., Menon U., MacDonald N. et al. Calculation of the risk of ovarian cancer from serial CA-125 values for preclinical detection in postmenopausal women. J Clin Oncol 2003;21(10 Suppl):206s–10s.Skates S.J., Menon U., MacDonald N. et al. Calculation of the risk of ovarian cancer from serial CA-125 values for preclinical detection in postmenopausal women. J Clin Oncol 2003;21(10 Suppl):206s–10s.26. Люстик А.В. Ультразвуковые и молекулярно-биологические критерии ранней диагностики рака яичников. Автореф. дис. … канд. мед. наук. М., 2012. [Lyustik A.V. Ultrasound and molecular-biological criteria of early diagnosis of ovarian cancer. Author's abstract of thesis ... of candidate of medical sciences. Moscow, 2012. (In Russ.)].Люстик А.В. Ультразвуковые и молекулярно-биологические критерии ранней диагностики рака яичников. Автореф. дис. … канд. мед. наук. М., 2012. [Lyustik A.V. Ultrasound and molecular-biological criteria of early diagnosis of ovarian cancer. Author's abstract of thesis ... of candidate of medical sciences. Moscow, 2012. (In Russ.)].27. Озерская Н.А., Агеева М.И. Ультразву- ковая диагностика опухолей яичников. Ультразвуковая и функциональная диагностика 2005;4:127. [Ozerskaya N.A., Ageeva M.I. Ultrasound diagnosis of ovarian tumors. Ul'trazvukovaya i funktsional'naya diagnostika = Ultrasound and functional diagnostics 2005;4:127. (In Russ.)].Озерская Н.А., Агеева М.И. Ультразву- ковая диагностика опухолей яичников. Ультразвуковая и функциональная диагностика 2005;4:127. [Ozerskaya N.A., Ageeva M.I. Ultrasound diagnosis of ovarian tumors. Ul'trazvukovaya i funktsional'naya diagnostika = Ultrasound and functional diagnostics 2005;4:127. (In Russ.)].28. Когай С.В. Возможности сонографии, позитронно-эмиссионной томографии и серологического метода исследования в диагностике рецидивов рака яичников. Дис. … канд. мед. наук. М.: 2013. С. 116–7. [Kogay S.V. Opportunities of sonography, positron-emissive tomography and serological method of studies in the diagnosis of ovarian cancer recurrence. Thesis ... of doctor of medical sciences. Moscow, 2013. Pp. 116–7. (In Russ.)].Когай С.В. Возможности сонографии, позитронно-эмиссионной томографии и серологического метода исследования в диагностике рецидивов рака яичников. Дис. … канд. мед. наук. М.: 2013. С. 116–7. [Kogay S.V. Opportunities of sonography, positron-emissive tomography and serological method of studies in the diagnosis of ovarian cancer recurrence. Thesis ... of doctor of medical sciences. Moscow, 2013. Pp. 116–7. (In Russ.)].29. Jacobs I., Oram D., Fairbanks J. et al. A risk of malignancy index incorporating CA-125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. Br J Obstet Gynаecol 1990;97(10):922–9.Jacobs I., Oram D., Fairbanks J. et al. A risk of malignancy index incorporating CA-125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. Br J Obstet Gynаecol 1990;97(10):922–9.30. Козаченко В.П. Клиническая онколо- гия. Руководство для врачей. М.: Медици- на, 2005. 376 с. [Kozachenko V.P. Clinical Oncology. Guidelines for doctors. Moscow: Meditsina, 2005. 376 p. (In Russ.)].Козаченко В.П. Клиническая онколо- гия. Руководство для врачей. М.: Медици- на, 2005. 376 с. [Kozachenko V.P. Clinical Oncology. Guidelines for doctors. Moscow: Meditsina, 2005. 376 p. (In Russ.)].31. http://gyn-endo.ru/wp-content/uploads/2012/08/info20.pdf.http://gyn-endo.ru/wp-content/uploads/2012/08/info20.pdf.32. Zhang B., Barekati Z., Kohler C. et al. Proteomics and biomarkers for ovarian cancer diagnosis. Ann Clin Lab Sci 2010;40(3): 218–25.Zhang B., Barekati Z., Kohler C. et al. Proteomics and biomarkers for ovarian cancer diagnosis. Ann Clin Lab Sci 2010;40(3): 218–25.33. Makridakis M., Vlahou A. Secretome proteomics for discovery of cancer biomarkers. J Proteomics 2010;73(12):2291–305.Makridakis M., Vlahou A. Secretome proteomics for discovery of cancer biomarkers. J Proteomics 2010;73(12):2291–305.34. Buys S.S., Partridge E., Black A. et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JАМА 2011;305(22): 2295–303.Buys S.S., Partridge E., Black A. et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JАМА 2011;305(22): 2295–303.35. Koprowski H., Herlyn M., Steplewski Z., Sears H.F. Specific antigen in serum of patients with colon carcinoma. Science 1981; 212(4490):53–5.Koprowski H., Herlyn M., Steplewski Z., Sears H.F. Specific antigen in serum of patients with colon carcinoma. Science 1981; 212(4490):53–5.36. Husseinzadeh N. Status of tumor markers in epithelial ovarian cancer has there been any progress? A review. Gynecol Oncol 2011;120(1):152–7.Husseinzadeh N. Status of tumor markers in epithelial ovarian cancer has there been any progress? A review. Gynecol Oncol 2011;120(1):152–7.37. http://www.aafp.org/afp/2005/0215/p759. html.http://www.aafp.org/afp/2005/0215/p759. html.38. ACOG committee opinion. Role of loop electrosurgical excision procedure in the evaluation of abnormal Pap test results. Number 195, November 1997. Committee on Gynecologic Practice. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 1998;61(2):203–4.ACOG committee opinion. Role of loop electrosurgical excision procedure in the evaluation of abnormal Pap test results. Number 195, November 1997. Committee on Gynecologic Practice. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 1998;61(2):203–4.39. Brown D.L., Andreotti R.F., Lee S.I. et al. ACR appropriateness criteria© ovarian cancer screening. Ultrasound Q 2010;26(4):219–23.Brown D.L., Andreotti R.F., Lee S.I. et al. ACR appropriateness criteria© ovarian cancer screening. Ultrasound Q 2010;26(4):219–23.40. Menon U., Gentry-Maharaj A., Hallett R. et al. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol 2009;10(4):327–40.Menon U., Gentry-Maharaj A., Hallett R. et al. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol 2009;10(4):327–40.41. Ашрафян Л.А., Ивашина С.И., Когай Н.В. и др. Возможности соноэластометрии для дифференциальной диагностики доброкачественных и злокачественных опухолей яичников. Опухоли женской репродуктивной системы 2012;2:55–8. [Ashrafyan L.A., Ivashina S.I., Kogay N.V. et al. Opportunities of ultrasound elastometry for the differential diagnosis of benign and malignant ovarian tumors. Opuholi zhenskoi reproduktivnoi sistemy = Tumors of the female reproductive system 2012;2:55–8. (In Russ.)].Ашрафян Л.А., Ивашина С.И., Когай Н.В. и др. Возможности соноэластометрии для дифференциальной диагностики доброкачественных и злокачественных опухолей яичников. Опухоли женской репродуктивной системы 2012;2:55–8. [Ashrafyan L.A., Ivashina S.I., Kogay N.V. et al. Opportunities of ultrasound elastometry for the differential diagnosis of benign and malignant ovarian tumors. Opuholi zhenskoi reproduktivnoi sistemy = Tumors of the female reproductive system 2012;2:55–8. (In Russ.)].42. Risum S., Høgdall C., Loft A. et al. The diagnostic value of PET/CT for primary ovarian cancer – a prospective study. Gynecol Oncol 2007;105(1):145–9.Risum S., Høgdall C., Loft A. et al. The diagnostic value of PET/CT for primary ovarian cancer – a prospective study. Gynecol Oncol 2007;105(1):145–9.43. Полев Д., Баранова А. Диагностические биомаркеры в онкогинекологии: критиче- ский взгляд. Онкогинекология 2012;4:4–12. [Polev D., Baranova A. Diagnostic biomarkers in gynecological oncology: a critical look. Onkoginekologiya = Oncogynecology 2012;4:4–12. (In Russ.)].Полев Д., Баранова А. Диагностические биомаркеры в онкогинекологии: критиче- ский взгляд. Онкогинекология 2012;4:4–12. [Polev D., Baranova A. Diagnostic biomarkers in gynecological oncology: a critical look. Onkoginekologiya = Oncogynecology 2012;4:4–12. (In Russ.)].44. http://www.fda.gov/NewsEvents/ Newsroom/PressAnnouncements/ucm182057. htm.http://www.fda.gov/NewsEvents/ Newsroom/PressAnnouncements/ucm182057. htm.45. Zhang Z., Chan D.W. The road from discovery to clinical diagnostics: lessons learned from the first FDA-cleared in vitro diagnostic multivariate index assay of proteomic biomarkers. Cancer Epidemiol Biomarkers Prev 2010;19(12):2995–9.Zhang Z., Chan D.W. The road from discovery to clinical diagnostics: lessons learned from the first FDA-cleared in vitro diagnostic multivariate index assay of proteomic biomarkers. Cancer Epidemiol Biomarkers Prev 2010;19(12):2995–9.46. Ware Miller R., Smith A., DeSimone C.P. et al. Performance of the American College of Obstetricians and Gynecologists’ ovarian tumor referral guidelines with a multivariate index assay. Obstet Gynecol 2011;117(6): 1298–306.Ware Miller R., Smith A., DeSimone C.P. et al. Performance of the American College of Obstetricians and Gynecologists’ ovarian tumor referral guidelines with a multivariate index assay. Obstet Gynecol 2011;117(6): 1298–306.47. Ueland F.R., Desimone C.P., Seamon L.G. et al. Effectiveness of a multivariate index assay in the preoperative assessment of ovarian tumors. Obstet Gynecol 2011;117(6):1289–97.Ueland F.R., Desimone C.P., Seamon L.G. et al. Effectiveness of a multivariate index assay in the preoperative assessment of ovarian tumors. Obstet Gynecol 2011;117(6):1289–97.48. Cramer D.W., Bast R.C. Jr., Berg C.D. et al. Ovarian cancer biomarker performance in prostate, lung, colorectal, and ovarian cancer screening trial specimens. Cancer Prev Res (Phila) 2011;4(3):365–74.Cramer D.W., Bast R.C. Jr., Berg C.D. et al. Ovarian cancer biomarker performance in prostate, lung, colorectal, and ovarian cancer screening trial specimens. Cancer Prev Res (Phila) 2011;4(3):365–74.49. Drapkin R., von Horsten H.H., Lin Y. et al. Human epididymis protein4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res 2005;65(6):2162–9.Drapkin R., von Horsten H.H., Lin Y. et al. Human epididymis protein4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res 2005;65(6):2162–9.50. Сергеева Н.С., Маршутина Н.В. Опухо- леассоциированные маркеры в скрининго- вых программах, направленных на активное выявление рака яичников: реальность, проблемы и перспективы. Практическая онкология 2010;11(2):110–9. [Sergeeva N.S., Marshutina N.V. Tumor associated markers in screening programs aimed at active detection of ovarian cancer: reality, problems and prospects. Prakticheskaya onkologiya = Practical Oncology 2010;11(2):110–9. (In Russ.)].Сергеева Н.С., Маршутина Н.В. Опухо- леассоциированные маркеры в скрининго- вых программах, направленных на активное выявление рака яичников: реальность, проблемы и перспективы. Практическая онкология 2010;11(2):110–9. [Sergeeva N.S., Marshutina N.V. Tumor associated markers in screening programs aimed at active detection of ovarian cancer: reality, problems and prospects. Prakticheskaya onkologiya = Practical Oncology 2010;11(2):110–9. (In Russ.)].51. Obiezu C.V., Scorilas A., Katsaros D. et al. Higher human kallikrein gene 4 (KLK4) expres- sion indicates poor prognosis of ovarian cancer patients. Clin Cancer Res 2001;7(8):2380–6.Obiezu C.V., Scorilas A., Katsaros D. et al. Higher human kallikrein gene 4 (KLK4) expres- sion indicates poor prognosis of ovarian cancer patients. Clin Cancer Res 2001;7(8):2380–6.52. Huhtinen K., Suvitie P., Hiissa J. et al. Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. Br J Cancer 2009;100(8):1315–9.Huhtinen K., Suvitie P., Hiissa J. et al. Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. Br J Cancer 2009;100(8):1315–9.53. Holcomb K., Vucetic Z., Miller M.C., Knapp R.C. Human epididymis protein 4 offers superior specifi city in the differentiation of benign and malignant adnexal masses in premenopausal women. Am J Obstet Gynecol 2011;205(4):358.e1–6.Holcomb K., Vucetic Z., Miller M.C., Knapp R.C. Human epididymis protein 4 offers superior specifi city in the differentiation of benign and malignant adnexal masses in premenopausal women. Am J Obstet Gynecol 2011;205(4):358.e1–6.54. Moore R.G., McMeekin D.S., Brown A.K. et al. A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecol Oncol 2009;112(1):40–6.Moore R.G., McMeekin D.S., Brown A.K. et al. A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecol Oncol 2009;112(1):40–6.55. http://www.arrayit.com/Microarray_ Diagnostics/OvaDx_Ovarian_Cancer_Test/ ovadx_ovarian_cancer_test.html.http://www.arrayit.com/Microarray_ Diagnostics/OvaDx_Ovarian_Cancer_Test/ ovadx_ovarian_cancer_test.html.