Immunological detection of bone marrow lesions in skin melanoma and its clinical significance: Observational study

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Background. Melanoma of the skin is characterized by a rapid progression and early metastasis. It has been shown the disseminated tumor cells, which are often found in the bone marrow, has an important prognostic value. The study of disseminated tumor cells in melanoma might be one of the possible additional sources of information about the nature of the disease and potential application points for drug therapy.

Aim. To study the frequency of detection of disseminated tumor cells in the bone marrow in melanoma, depending on the clinical and morphological characteristics of the tumor.

Materials and methods. The study included 67 patients with a verified diagnosis of melanoma who were examined and treated at the Blokhin National Medical Research Center of Oncology from 2014 to 2019 years. Male patients accounted for 50.7% (n=34), female patients 49.3% (n=33). The average age of patients: 50.1±1.6 years. Immunological and morphological examination of the bone marrow were perfomed. Morphological examination was performed by two independent morphologists. Disseminated tumor cells were evaluated by flow cytometry among all nucleated cells (Syto41+) based on the expression of the HMB-45 antigen and the absence of expression of the CD45 panleukocyte antigen (FACS Canto II, USA, Kaluza Analysis v2.1). Statistical data processing was performed using the IBM-SPSS Statistics v.21

Results. Morphologically bone marrow damage was not detected in any case. Disseminated tumor cells (CD45-HMB-45+) in the bone marrow of melanoma patients were detected in 62.7% (n=42) of cases by flow cytometry. The frequency of bone marrow damage in the early stages is not lower than in advanced ones (p=0.029). This is clearly seen in the enlarged analysis. The percentage of DTC detection. At stages I and II was 60.0% (6/10) and 84.6% (11/13), respectively, at stages III and IV – 44.4% (8/18) and 65.4% (17/26). In addition, the frequency of detection of disseminated tumor cells in the bone marrow was higher in young patients (p=0.02). There was no correlation between the frequency of bone marrow damage depending on BRAF status.

Conclusion. The connection of disseminated tumor cells with the clinical and morphological characteristics of the melanoma has been established. Melanoma is characterized by frequent bone marrow damage, even in the early stages, in young patients.

作者简介

Maria Krylovetskaya

Blokhin National Medical Research Center of Oncology

编辑信件的主要联系方式.
Email: mariyakrilo@gmail.com
ORCID iD: 0000-0002-0868-3948

Endoscopist, Blokhin National Medical Research Center of Oncology

俄罗斯联邦, Moscow

Svetlana Chulkova

Blokhin National Medical Research Center of Oncology; Pirogov Russian National Research Medical University

Email: chulkova@mail.ru
ORCID iD: 0000-0003-4412-5019

Cand. Sci. (Med.), Assoc. Prof., Blokhin National Medical Research Center of Oncology, Pirogov Russian National Research Medical University

俄罗斯联邦, Moscow; Moscow

Irina Markina

Blokhin National Medical Research Center of Oncology

Email: irina160771@yandex.ru

Cand. Sci. (Med.), Blokhin National Medical Research Center of Oncology

俄罗斯联邦, Moscow

Olga Chernysheva

Blokhin National Medical Research Center of Oncology

Email: mariyakrilo@gmail.com

Cand. Sci. (Med.), Assoc. Prof., Blokhin National Medical Research Center of Oncology

俄罗斯联邦, Moscow

Igor Komarov

Blokhin National Medical Research Center of Oncology

Email: komaroving@mail.ru
ORCID iD: 0000-0002-3495-5521

D. Sci. (Med.), Prof., Blokhin National Medical Research Center of Oncology

俄罗斯联邦, Moscow

Olga Kolbatskaya

Blokhin National Medical Research Center of Oncology

Email: helgaopk69@yandex.ru
ORCID iD: 0000-0001-8493-9012

Cand. Sci. (Med.), Blokhin National Medical Research Center of Oncology

俄罗斯联邦, Moscow

Natalya Kupryshina

Blokhin National Medical Research Center of Oncology

Email: natalya-2511@yandex.ru

Cand. Sci. (Med.), Blokhin National Medical Research Center of Oncology

俄罗斯联邦, Moscow

Andrey Logachev

Blokhin National Medical Research Center of Oncology

Email: Andr1979l@yandex.ru

Daily Hospital Doctor, Blokhin National Medical Research Center of Oncology

俄罗斯联邦, Moscow

Irina Mikhaylova

Blokhin National Medical Research Center of Oncology

Email: irmikhaylova@gmail.com
ORCID iD: 0000-0002-7659-6045

D. Sci. (Med.), Blokhin National Medical Research Center of Oncology

俄罗斯联邦, Moscow

Lev Demidov

Blokhin National Medical Research Center of Oncology

Email: demidov.lev@gmail.com

D. Sci. (Med.), Prof., Blokhin National Medical Research Center of Oncology

俄罗斯联邦, Moscow

Nikolai Tupitsyn

Blokhin National Medical Research Center of Oncology

Email: nntca@yahoo.com
ORCID iD: 0000-0003-3966-128X

D. Sci. (Med.), Prof., Blokhin National Medical Research Center of Oncology

俄罗斯联邦, Moscow

参考

  1. Блинов Н.Н., Константинова М.М. Меланома кожи. Факторы риска и прогноза. Onconews. 2004;4:2-4 [Blinov NN, Konstantinova MM. Melanoma kozhi. Faktory riska i prognoza. Onconews. 2004;4:2-4 (in Russian)].
  2. Злокачественные новообразования в России в 2019 году (заболеваемость и смертность). Под ред. О.В. Каприна, В.В. Старинского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИРЦ» Минздрава России, 2019 [Zlokachestvennyie novoobrazovaniia v Rossii v 2019 godu (zabolevaiemost' i smertnost'). Pod red. OV Kaprina, VV Starinskogo, GV Petrovoi. Moscow: MNIOI im. PA Gertsena – filial FGBU NMIRTS Minzdrava Rossii, 2019 (in Russian)].
  3. Анисимов В.В. Содержание понятия «местный рецидив» после хирургического лечения злокачественной меланомы кожи. Вопросы онкологии. 1985;31(1):32-7 [Anisimov VV. Soderzhaniie ponyatiia “mestnyi retsidiv” posle khirurgicheskogo lecheniia zlokachestvennoi melanomy kozhi. Voprosy onkologii. 1985;31(1):32-7 (in Russian)].
  4. Фрадкин С.З., Залуцкий И.В. Меланома кожи. Минск: Беларусь, 2000 [Fradkin SZ, Zalutskii IV. Melanoma kozhi. Minsk: Belarus', 2000 (in Russian)].
  5. Nambiar S, Mirmohammadsadegh A, Doroudi R, et al. Signaling networks in cutaneous melanoma metastasis identified by complementary DNA microarrays. Arch Dermatol. 2005;141(2):165-73.
  6. Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol. 2001;19(16):3635-48.
  7. Balch СМ, Soong SJ, Shaw HM, et al. An analysis of prognostic factors in 8.500 patients with cutaneous melanoma. Eds СМ Balch, AN Houghton, GW Milton, et al. Cutaneous Melanoma, 2nd ed. Philadelphia: J.B. Lippincott, 1992; p. 165.
  8. MacKie RM. Incidence, risk factors and prevention of melanoma. Eur J Cancer. 1998;34(Suppl. 3):S3-6.
  9. Nambisan N. Early metastatic patterns and survival in malignant melanoma. J Surg Oncol. 1987;34(4):248-52.
  10. Braun S, Vogl FD, Naume B, et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med. 2005;353(8):793-802. doi: 10.1056/NEJMoa050434
  11. Alix-Panabires C, Muller V, Pantel K. Current status in human breast cancer micro- metastasis. Curr Opin Oncol. 2007;19(6):558-63. doi: 10.1097/CCO.0b013e3282f0ad79
  12. Тупицын Н.Н. Костный мозг онкологического больного: стадирование опухолей, гемопоэз, иммунная система. Иммунология гемопоэза. 2018;16(2):10-54 [Tupitsyn NN. Kostnyi mozg onkologicheskogo bol'nogo: stadirovanie opukholei, gemopoez, immunnaia sistema. Immunologiia gemopoeza. 2018;16(2):10-54 (in Russian)].
  13. Тупицын Н.Н. Циркулирующие и диссеминированные раковые клетки при раке молочной железы и раке яичников. Онкогинекология. 2013;1:12-8 [Tupitsyn NN. Circulating and disseminated tumor cells in breast cancer and ovarian cancer. Onkoginekologiia. 2013;1:12-8 (in Russian)].
  14. Бесова Н.С., Обаревич Е.С., Давыдов М.М., и др. Прогностическое значение диссеминированных опухолевых клеток в костном мозге больных диссеминированным раком желудка до начала противоопухолевой терапии. Фарматека. 2017;17(350):62-6 [Besova NS, Obarevich YeS, Davydov MM, et al. Prognosticheskoie znacheniie disseminirovannykh opukholevykh kletok v kostnom mozge bol'nykh disseminirovannym rakom zheludka do nachala protivoopukholevoi terapii. Farmateka. 2017;17(350):62-6 (in Russian)].
  15. Рябчиков Д.А., Безнос О.А., Дудина И.А., и др. Диссеминированные опухолевые клетки у пациентов с люминальным раком молочной железы. Российский биотерапевтический журнал. 2018;17(1):53-7 [Ryabchikov DA, Beznos OA, Dudina IA, et al. Disseminated tumor cells in patients with luminal breast cancer. Russian Biotherapeutic Journal. 2018;17(1):53-7 (in Russian)]. doi: 10.17650/1726- 9784-2018-17-1-53-57
  16. Lilleby W, Stensvold A, Mills IG, Nesland JM. Disseminated tumor cells and their prognostic significance in nonmetastatic prostate cancer patients. Int J Cancer. 2013;133(1):149-55.
  17. Flatmark K, Borgen E, Nesland JM, et al. Disseminated tumour cells as a prognostic biomarker in colorectal cancer. Br J Cancer. 2011;104(9):1434-9.
  18. Чулкова С.В., Тупицын Н.Н., Джуманазаров Т.М., и др. Обнаружение диссеминированных опухолевых клеток в костном мозге больных немелкоклеточным раком легкого. Российский биотерапевтический журнал. 2020;19(3):29-37 [Chulkova SV, Tupitsyn NN, Djumanazarov TM, et al. Detection of disseminated tumor cells in the bone marrow of patients with non-small cell lung cancer. Russian Journal of Biotherapy. 2020;19(3):29-37 (in Russian)].
  19. Маркина И.Г., Тупицын Н.Н., Михайлова И.Н., Демидов Л.В. Гематогенное метастазирование опухолей: ключевые моменты и эволюционирующие парадигмы. Иммунология гемопоэза. 2018;6(1):109-32 [Markina IG, Tupitsyn NN, Mikhailova IN, Demidov LV. Gematogennoe metastazirovanie opukholei: kliuchevie momenty i evoliutsioniruiushchie paradigmy. Immunologiia gemopoeza. 2018;6(1):109-32 (in Russian)].
  20. Bartkowiak K, Effenberger KE, Harder S, et al. Discovery of a novel unfolded protein response phenotype of cancer stem/progenitor cells from the bone marrow of breast cancer patients. J Proteome Res. 2010;9(6):3158-68.
  21. Chernysheva O, Markina I, Demidov L, et al. Bone marrow involvement in melanoma. Potentials for detection of disseminated tumor cells and characterization of their subsets by flow cytometry. Cells. 2019;8(6):627. doi: 10.3390/cells8060627
  22. Чулкова С.В., Чернышева О.А., Маркина И.Г., и др. Стволовые опухолевые клетки меланомы. Поражение костного мозга. Обзор и представление собственных данных. Вестник Российского научного центра рентгенрадиологии. 2019;19(4):182-97 [Chulkova SV, Chernysheva OA, Markina IG, et al. Stem tumor cells of melanoma. Bone marrow involvement. Review and own data. Vestnik Rossiiskogo nauchnogo tsentra rentgenradiologii. 2019;19(4):182-97 (in Russian)].
  23. Sai B, Xiang J. Disseminated tumour cells in bone marrow are the source of cancer relapse after therapy. J Cell Mol Med. 2018;22(12):5776-86.
  24. Чулкова С.В., Маркина И.Н., Антипова А.С., и др. Роль опухолевых стволовых клеток в прогнозе и канцерогенезе меланомы. Вестник Российского научного центра рентгенрадиологии Минздрава России. 2018;18(4):100-16 [Chulkova SV, Markina IG, Antipova AS, et al. The role of stem tumor cells in caricogenesis and the forecast of melanoma. Vestnik Rossiiskogo nauchnogo tsentra rentgenradiologii Minzdrava Rossii. 2018;18(4):100-16 (in Russian)].
  25. Nguyen DX, Bos PD, Massagué J. Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer. 2009;9(4):274-84.
  26. Janni W, Vogl FD, Wiedswang G, et al. Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse – a European pooled analysis. Clin Cancer Res. 2011;17(9):2967-76.
  27. 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.
  28. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-74. doi: 10.1016/j.cell.2011.02.013
  29. Schatton T, Frank MH. Cancer stem cells and human malignant melanoma. Pigment Cell Melanoma Res. 2008;21(1):39-55. doi: 10.1111/j.1755-148X.2007.00427.x
  30. Wang Z, Ouyang G. Periostin: a bridge between cancer stem cells and their metastatic niche. Cells Stem Cells. 2012;10(2):111-2. doi: 10.1016/j.stem.2012.01.002
  31. Франк Г.А., Завалишина Л.Э., Кекеева Т.В., и др. Первое Всероссийское молекулярно-эпидемиологическое исследование меланомы: результаты анализа мутаций в гене BRAF. Архив патологии. 2014;76(3):65-73 [Frank GA, Zavalishina LÉ, Kekeeva TV, et al. First Russian nationwide molecular epidemiological study for melanoma: results of BRAF mutation analysis. Arkhiv Patologii. 2014;76(3):65-73 (in Russian)].

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1. JATS XML
2. Fig. 1. Distribution of patients with melanoma by age.

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3. Fig. 2. The detection rate of disseminated tumor cells (DTC) in the bone marrow of patients with melanoma.

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4. Fig. 3. Detection of DTC in the bone marrow of patients with skin melanoma using flow cytometry.

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5. Fig. 4. The detection rate of DTC in the bone marrow depending on the primary tumor site.

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6. Fig. 5. Bone marrow involvement rate in the early and advanced stages of melanoma.

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