Russian Journal of BiotherapyRussian Journal of BiotherapyРоссийский биотерапевтический журнал1726-97841726-9792Publishing House ABV Press138610.17650/1726-9784-2023-22-2-20-26REVIEWSОБЗОРЫ ЛИТЕРАТУРЫClinical significance of detection of micrometastases in lymph nodes in ovarian cancerКлиническая значимость обнаружения микрометастазов в лимфатических узлах при раке яичниковhttps://orcid.org/0000-0002-9486-2028AldushkinaYu. V.АлдушкинаЮ. В.
Russian Federation

Yulia Vladimirovna Aldushkina

Bld. 1, 51 3rd Parkovaya St., Moscow 105425

Юлия Владимировна Алдушкина

105425 Москва, 3‑я Парковая ул., 51, стр. 1

juliaald@mail.ruhttps://orcid.org/0000-0002-4370-6578AnisimovaN. Yu.АнисимоваН. Ю.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522;

4 Leninskiy Ave., 119049 Moscow

115522 Москва, Каширское шоссе, 24;

119049 Москва, Ленинский пр-кт, 4

https://orcid.org/0000-0001-5235-6509GritsaiA. N.ГрицайА. Н.
Russian Federation

Bld. 1, 51 3rd Parkovaya St., Moscow 105425

105425 Москва, 3‑я Парковая ул., 51, стр. 1

https://orcid.org/0000-0002-0773-255XNovruzovK. M.НоврузовК. М.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

https://orcid.org/0000-0003-2138-7323DolzhikovaYu. I.ДолжиковаЮ. И.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

https://orcid.org/0000-0001-5418-7403OdaryukO. A.ОдарюкО. А.
Russian Federation

16 Michurinskiy Prospect, 119602

119602 Москва, Мичуринский пр-кт, 16

https://orcid.org/0000-0002-9943-3054FilonenkoD. V.ФилоненкоД. В.
Russian Federation

Bld. 6, 86 Shosse Entuziastov, 111123 Moscow

111123 Москва, шоссе Энтузиастов, 86, стр. 6

N. A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – branch of the National Medical Research Radiological Centre, Ministry of Health of RussiaНаучно-исследовательский институт урологии и интервенционной радиологии им. Н. А. Лопаткина – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава РоссииN. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н. Н. Блохина» Минздрава РоссииNational University of Science and Technology «MISIS»ФГАОУ ВО «Национальный исследовательский технологический университет «МИСиС»City Polyclinic № 8, Moscow Healthcare DepartmentГБУЗ «Городская поликлиника № 8 Департамента здравоохранения города Москвы»A. S. Loginov Moscow Clinical Scientific Center, Moscow Healthcare DepartmentГБУЗ «Московский клинический научный центр им. А. С. Логинова Департамента здравоохранения города Москвы»1507202322220261407202314072023https://bioterapevt.abvpress.ru/jour/article/view/1386

Ovarian cancer of epithelial origin is the most common type of oncological process in this organ and is characterized by a high probability of fatal outcome. It is believed that this is due to insufficiently effective diagnosis of the prevalence and severity of this disease. This review presents data on the development of disease recurrence in a significant number of patients after cytoreductive surgery. According to some authors, the reason for the high risk of recurrence is the insufficient information content of the method of studying histological preparations of regional lymph nodes after staining with hematoxylin and eosin to detect small-sized metastases, including isolated tumor cells and micrometastases. To improve the accuracy of such diagnostics, it is recommended to supplement the study of multilevel sections of lymph nodes using routine staining with the use of immunohistochemistry and other methods using various antibodies to cytokeratins, along with other epithelial markers. The review provides an analysis of the opinions of various researchers on the prognostic significance of the detection of micrometastases in the lymph nodes, which can increase the effectiveness of therapy due to a more accurate assessment of the prevalence of the disease and correction of the tactics of treating patients with various oncological diseases.

Рак яичников является самой частой разновидностью онкологического процесса в этом органе и характеризуется высокой вероятностью летального исхода. Считается, что это обусловлено недостаточно эффективной диагностикой распространенности и тяжести указанного заболевания. В настоящем обзоре приведены данные о развитии рецидива заболевания у значимого числа пациентов после циторедуктивного хирургического вмешательства. По мнению ряда авторов, причиной высокого риска рецидива является недостаточная информативность метода изучения гистологических препаратов регионарных лимфатических узлов после окраски гематоксилином и эозином для выявления метастазов небольшого объема, включая изолированные опухолевые клетки и микрометастазы. Для повышения точности такой диагностики рекомендовано дополнить изучение многоуровневых срезов лимфатических узлов с использованием рутинного окрашивания применением иммуногистохимии и других методов с использованием различных антител к цитокератинам наряду с другими эпителиальными маркерами. В обзоре приводится анализ мнений различных исследователей о прогностической значимости обнаружения микрометастазов в лимфатических узлах, что может повысить эффективность терапии за счет более точной оценки распространенности заболевания и коррекции тактики лечения пациентов с различными онкологическими заболеваниями.

ovarian cancermicrometastaseslymph nodetumor cellscytokeratinрак яичниковмикрометастазылимфатический узелопухолевые клеткицитокератинIARC, WHO. Ovary. Cancer Over Time, Dec. 2020. Available at: https://gco.iarc.fr/today/data/factsheets/cancers/25-Ovary-factsheet.pdf. Accessed 14 Dec, 2022.Wang Y.-Ch., Wu R.-Ch., Jung Sh.-M. et al. Detection and prognostic significance of isolated tumor cells and micrometastases in pelvic lymph nodes of patients with early ovarian clear cell carcinoma. J Formos Med Assoc 2021;120(10):1869–75. DOI: 10.1016/j.jfma.2021.03.028Solopova A.E., Chashchin A.A., Solopova A.G., Makatsariya A.D. Current opinions concerning the pathogenesis of epithelial ovarian cancer and new diagnostic approaches to the disease. Akusherstvo, ginekologiya i reproduktsia = Obstetrics, Gynecology and Reproduction 2016;10(1):75–83. (In Russ.). DOI: 10.17749/2313-7347.2015.10.1.075-083Солопова А.Е., Чащин А.А., Солопова А.Г., Макацария А.Д. Современные взгляды на патогенез и возможности диагностики эпителиального рака яичников. Акушерство, гинекология и репродукция 2016;10(1):75–83. DOI: 10.17749/2313-7347.2015.10.1.075-083Vaughan S., Coward J.I., Bast R.C. Jr. et al. Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer 2011;11(10):719–25. DOI: 10.1038/nrc3144Wright P.K., McVey R.J., Wilkinson N. Specimen cut-up. In: Pathology of the ovary, fallopian tube and peritoneum. Essentials of diagnostic gynecological pathology. Ed. by N. Wilkinson. Springer, London, 2014. P. 481–496. DOI: 10.1007/978-1-4471-2942-4_20Del Carmen M.G., Birrer M., Schorge J.O. Clear cell carcinoma of the ovary: a review of the literature. Gynecol Oncol 2012;126(3):481–90. DOI: 10.1016/j.ygyno.2012.04.021Chan J.K., Teoh D., Hu J.M. et al. Do clear cell ovarian carcinomas have poorer prognosis compared to other epithelial cell types? A study of 1411 clear cell ovarian cancers. Gynecol Oncol 2008;109(3):370–6. DOI: 10.1016/j.ygyno.2008.02.006Sugiyama T., Kamura T., Kigawa J. et al. Clinical characteristics of clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy. Cancer 2000;88(11):2584–9.Ku F.-Ch., Wu R.-Ch., Yang L.-Y. et al. Clear cell carcinomas of the ovary have poorer outcomes compared with serous carcinomas: Results from a single-center Taiwanese study. J Formos Med Assoc 2018;117(2):117–25. DOI: 10.1016/j.jfma.2017.03.007Huang H.J., Yang L.Y., Tung H.J. et al. Management and clinical outcomes of patients with recurrent/progressive ovarian clear cell carcinoma. J Formos Med Assoc 2020;119(4):793–804. DOI: 10.1016/j.jfma.2019.11.018Hermanek P., Hutter R.V., Sobin L.H., Wittekind C. International Union Against Cancer. Classification of isolated tumor cells and micrometastasis. Cancer 1999;86(12):2668–73.Rosenberg R., Friederichs J., Gertler R. et al. Prognostic evaluation and review of immunohistochemically detected disseminated tumor cells in peritumoral lymph nodes of patients with pN0 colorectal cancer. Int J Colorectal Dis 2004;19(5): 430–7. DOI: 10.1007/s00384-003-0559-zFaerden A.E., Sjo O.H., Bukholm I.R. et al. Lymph node micrometastases and isolated tumor cells influence survival in stage I and II colon cancer. Dis Colon Rectum 2011;54(2):200–6. DOI: 10.1007/DCR.0b013e3181fd4c7cWaldman S.A., Hyslop T., Schulz S. et al. Association of GUCY2C expression in lymph nodes with time to recurrence and disease-free survival in pN0 colorectal cancer. JAMA 2009;301(7):745–52. DOI: 10.1001/jama.2009.141Hyslop T., Weinberg D.S., Schulz S. et al. Occult tumor burden predicts disease recurrence in lymph node-negative colorectal cancer. Clin Cancer Res 2011;17(10):3293–303. DOI: 10.1158/1078-0432.CCR-10-3113Ohta Y., Suzuki T., Shiokawa A. et al. Expression of CD10 and cytokeratins in ovarian and renal clear cell carcinoma. Int J Gynecol Pathol 2005;24(3):239–45. DOI: 10.1097/01.pgp.0000158533.28866.45Cooper D., Schermer A., Sun T.T. Classification of human epithelia and their neoplasms using monoclonal antibodies to keratins: strategies, applications, and limitations. Lab Invest 1985;52(3):243–56.Suzuki M., Ohwada M., Saga Y. et al. Micrometastatic p53-positive cells in the lymph nodes of early stage epithelial ovarian cancer: prognostic significance. Oncology 2001;60(2):170–5. DOI: 10.1159/000055315Maehara Y., Oshiro T., Endo K. et al. Clinical significance of occult micrometastasis lymph nodes from patients with early gastric cancer who died of recurrence. Surgery 1996;119(4):397– 402. DOI: 10.1016/s0039-6060(96)80138-3Lee E., Chae Y., Kim I. et al. Prognostic relevance of immunohistochemically detected lymph node micrometastasis in patients with gastric carcinoma. Cancer 2002;94(11):2867–73. DOI: 10.1002/cncr.10562Yasuda K., Adachi Y., Shiraishi N. et al. Prognostic effect of lymph node micrometastasis in patients with histologically node-negative gastric cancer. Ann Surg Oncol 2002;9(8):771–4. DOI: 10.1007/BF02574499Juretzka M.M., Jensen K.C., Longacre T.A. et al. Detection of pelvic lymph node micrometastasis in stage IA2-IB2 cervical cancer by immunohistochemical analysis. Gynecol Oncol 2004;93(1):107–11. DOI: 10.1016/j.ygyno.2003.11.033Lentz S.E., Muderspach L.I., Felix J.C. et al. Identification of micrometastases in histologically negative lymph nodes of early-stage cervical cancer patients. Obstet Gynecol 2004;103(6):1204–10. DOI: 10.1097/01.AOG.0000125869.78251.5eDelomenie M., Bonsang-Kitzis H., Bats A.S. et al. The clinical implication of lymph nodes micrometastases and isolated tumor cells in patients with cervical cancer: a systematic review. Eur J Obstet Gynecol Reprod Biol 2019;241:71–6. DOI: 10.1016/j.ejogrb.2019.08.010Amin M.B., Greene F.L., Edge S.B. et al. The Eighth Edition AJCC Cancer Staging Manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin 2017;67(2):93–9. DOI: 10.3322/caac.21388de Boer M., van Deurzen C.H., van Dijck J.A. et al. Micrometastases or isolated tumor cells and the outcome of breast cancer. N Engl J Med 2009;361(7):653–63. DOI: 10.1056/NEJMoa0904832Cote R.J., Peterson H.F., Chaiwun B. et al. Role of immunohistochemical detection of lymph-node metastasesin management of breast cancer. International Breast Cancer Study Group. Lancet 1999;354(9182):896–900. DOI: 10.1016/s0140-6736(98)11104-2Wong Y.P., Shah S.A., Shaari N. et al. Comparative analysis between multilevel sectioning with conventional haematoxylin and eosin staining and immunohistochemistry for detecting nodal micrometastases with stage I and II colorectal cancers. Asian Pac J Cancer Prev 2014;15(4):1725–30. DOI: 10.7314/apjcp.2014.15.4.1725Hara K., Kajita R., Torii K.U. et al. The secretory peptide gene EPF1 enforces the stomatal one-cell-spacing rule. Genes Dev 2007;21(14):1720–5. DOI: 10.1101/gad.1550707Linden M.D., Zarbo R.J. Cytokeratin immunostaining patterns of benign, reactive lymph nodes: applications for the evaluation of sentinel lymph node specimen. Appl Immunohistochem Mol Morphol 2001;9(4):297–301. DOI: 10.1097/00129039-200112000-00002Hermanek P. pTNM and residual tumor classifications: problems of assessment and prognostic significance. World J Surg 1995;19(2):184–90. DOI: 10.1007/BF00308624Edwards B.K., Ward E., Kohler B.A. et al. Annual report to the nation on the status of cancer, 1975–2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer 2010;116(3): 544–73. DOI: 10.1002/cncr.24760Natrah M.S., Ezat S., Syed M.A. et al. Quality of life in Malaysian colorectal cancer patients: a preliminary result. Asian Pac J Cancer Prev 2012;13(3):957–62. DOI: 10.7314/apjcp.2012.13.3.957American Joint Committee on Cancer. Ovary, fallopian tube, and primary peritoneal carcinoma. In: AJCC Cancer Staging Manual. 8th edn. New York, NY: Springer, 2017. P. 681–690.Akagi Y., Kinugasa T., Adachi Y., Shirouzu K. Prognostic significance of isolated tumor cells in patients with colorectal cancer in recent 10-year studies. Mol Clin Oncol 2013;1(4): 582–92. DOI: 10.3892/mco.2013.116Cassidy J. Guidelines for adjuvant therapy in colorectal cancer. Are they useful? And to whom? Clin Oncol (R Coll Radiol) 2011;23(5):312–3. DOI: 10.1016/j.clon.2010.06.001Komukai S., Nishimaki T., Watanabe H. et al. Significance of immunohistochemically demonstrated micrometastases to lymph nodes in esophageal cancer with histologically negative nodes. Surgery 2000;127(1):40–6. DOI: 10.1067/msy.2000.102754Xi L., Coello M.C., Litle V.R. et al. A combination of molecular markers accurately detects lymph node metastasis in non-small cell lung cancer patients. Clin Cancer Res 2006;12(8):2484–91. DOI: 10.1158/1078-0432.CCR-05-2037Iddings D., Ahmad A., Elashoff D., Bilchik A. The prognostic effect of micrometastases in previously staged lymph node negative (N0) colorectal carcinoma: a meta-analysis. Ann Surg Oncol 2006;13(11):1386–92. DOI: 10.1245/s10434-006-9120-yHaince J.F., Houde M., Beaudry G. et al. Comparison of histopathology and RT-qPCR amplification of guanylyl cyclase C for detection of colon cancer metastases in lymph nodes. J Clin Pathol 2010;63(6):530–7. DOI: 10.1136/jcp.2009.072983Nicastri D.G., Doucette J.T., Godfrey T.E., Hughes S.J. Is occult lymph node disease in colorectal cancer patients clinically significant? A review of the relevant literature. J Mol Diagn 2007;9(5):563–71. DOI: 10.2353/jmoldx.2007.070032Farshid G., Pradhan M., Kollias J., Gill P.G. Computer simulations of lymph node metastasis for optimizing the pathologic examination of sentinel lymph nodes in patients with breast carcinoma. Cancer 2000;89(12):2527–37.Dutta S.W., Volaric A., Morgan J.T. et al. Pathologic evaluation and prognostic implications of nodal micrometastases in breast cancer. Semin Radiat Oncol 2019;29(2):102–10. DOI: 10.1016/j.semradonc.2018.11.001