Клиническая значимость обнаружения микрометастазов в лимфатических узлах при раке яичников

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.

1. IARC, 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.

2. 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.2021.03.028

3. Солопова 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: 10.17749/2313-7347.2015.10.1.075-083

4. Vaughan 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/nrc3144

5. Wright 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_20

6. Del 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.2012.04.021

7. Chan 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.2008.02.006

8. Sugiyama 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.

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.2017.03.007

10. Huang 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.2019.11.018

11. Hermanek 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.

12. 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-z

13. Faerden 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.0b013e3181fd4c7c

14. Waldman 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.2009.141

15. Hyslop 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-10-3113

16. Ohta 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.0000158533.28866.45

17. Cooper 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.

18. 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: 10.1159/000055315

19. Maehara 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)80138-3

20. Lee 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.10562

21. Yasuda 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/BF02574499

22. Juretzka 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.2003.11.033

23. Lentz 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.0000125869.78251.5e

24. Delomenie 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.2019.08.010

25. Amin 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.21388

26. de 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/NEJMoa0904832

27. Cote 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)11104-2

28. Wong 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.2014.15.4.1725

29. Hara 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.1550707

30. Linden 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: 10.1097/00129039-200112000-00002

31. Hermanek P. pTNM and residual tumor classifications: problems of assessment and prognostic significance. World J Surg 1995;19(2):184–90. DOI: 10.1007/BF00308624

32. Edwards 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.24760

33. Natrah 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.2012.13.3.957

34. American 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.

35. 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.2013.116

36. Cassidy 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.2010.06.001

37. Komukai 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.2000.102754

38. Xi 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-05-2037

39. Iddings 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-y

40. Haince 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.2009.072983

41. Nicastri 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.2007.070032

42. Farshid 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.

43. 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