Cellular microenvironment of uveal melanoma: clinical and morphological correlations and predictors of bad prognosis


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Abstract

Introduction. Uveal melanoma is a malignant neoplasm of neuroectodermal origin, prone to early metastasis. The tumor microenvironment, including «inflammatory cells» and connective tissue cells, affects its progression, angiogenesis and metastasis. Purpose. To carry out clinical and morphological correlations of the cellular microenvironment of uveal melanoma with the detection of predictors of bad prognosis. Methods. 43 enucleated eyes with uveal melanoma (258 histological preparation) of adult patients were examined. Pathological type of tumors: epithelioid cell (n=9), spindle cell type AB (n=15), mixed cell (n=19). Tumor thickness - 4,7±1,3 mm, bazal diameter - 13,5±3,3 mm. T1N0M0 tumors in 6 eyes were detected, which were located juxtapapillary with involvement of the optic nerve head, which required enucleation. The presence and localization of lymphocytes, macrophages, mast cells, plasma cells, myeloid-derived suppressor cells (promyelocytes, neutrophils, eosinophils), fibroblasts and degree of tumor tissue infiltration were analyzed. Statistical methods: Microsoft Excel, Statistica 10.1, Spearman’s rank correlation coefficient - rs. Results. Analyzing the obtained results, we revealed higher correlations of the epithelium-cell type with the presence of macrophages, myeloid-derived suppressor cells (promyelocytes, neutrophils, eosinophils). The high degree of pigmentation correlated mainly with the presence of mast cells, myeloid-derived suppressor cells (promyelocytes, eosinophils), fibroblasts. The high degree of tumor vascularization correlated mainly with the presence of mast cells. At the same time, the moderate correlation between growth of tumor cells by emissaries with mast cells, myeloid-derived suppressor cells (promyelocytes, eosinophils), fibroblasts was noted. Conclusion. Thus, identification of certain cells in uveal melanoma microenvironment may be a predictor of an unfavorable tumor course and may serve as a pretext for the development of accompanying target therapy aimed to eliminating or reprogramming altered immunity cells and connective tissue.

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About the authors

S. V Saakyan

Helmholtz, Moscow Research Centre of Eye Diseases

G. P Zakharova

Helmholtz, Moscow Research Centre of Eye Diseases

E. B Myakoshina

Helmholtz, Moscow Research Centre of Eye Diseases

Email: myakoshina@mail.ru

References

  1. Каприн А.Д., Старинский В.В., Петрова Г.В. (ред.). Состояние онкологической помощи населению России в 2015 г. М.: МНИОИ им. П.А. Герцена - филиал ФГБУ НМИРЦ Минздрава России, 2016
  2. Бровкина А.Ф., Панова И.Е., Саакян С.В. Офтальмоонкология: новое за последние два десятилетия. Вестник офтальмологии. 2014;130 (6): 13-9
  3. Singh A.D., Turell M.E., Topham A.K. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology. 2011; 118: 1881-5. https://doi.org/10.10Wj. ophtha.2011.01.040
  4. Саакян С.В., Мякошина Е.Б., Кричевская Г.И., Слепова О.С., Пантелеева О.Г, Андрюшин А.С., Хорошилова-Маслова И.П., Захарова ГП. Обследование больных увеальной меланомой на наличие герпес-вирусных инфекций. Вопросы вирусологии. 2016; 61 (6): 284-7. http:// dx.doi.org/10.18821/0507-4088-2016-61-6-284-287 [Saakyan S.V, Myakoshina E.B., Krichevskaya G.I., Slepova O.S., Panteleeva O.G., Andryushin A.S., Khoroshilova-Maslova I.P., Zakharova G.P. Examination of patients with uveal melanoma for the presence of herpes viral infection. Voprosy virusologii. 2016; 61 (6): 284-7 (In Russian)]
  5. Саакян С.В., Амирян А.Г., Цыганков А.Ю., Склярова Н.В., Залетаев Д.В. Клинические, патоморфологические и молекулярно-генетические особенности увеальной меланомы с высоким риском метастазирования. Российский офтальмологический журнал. 2015; 8 (2): 47-52. [Saakyan S.V, Amiryan A.G., Tsygankov A.Yu., Sklyarova N.V, Zaletaev D.V. Clinical, pathological and molecular genetic features of uveal melanoma with a high risk of metastasis. Rossiyskiy oftal'mologicheskiy zhurnal. 2015; 8 (2): 47-52 (In Russian)]
  6. Зибиров РФ., Мозеров С.А. Характеристика клеточного микроокружения опухоли. Онкология. Журнал им. П.А. Герцена, 2018; 2: 67-72. https://doi. org/10.17116/onkolog20187267-72 [Zibirov R.F., Mozerov S.A. Characteristic of the cellular microenvironment of the tumor. Onkologiya. Zhurnal im. PA. Gertsena, 2018; 2: 67-72 (In Russian)]
  7. Roma-Rodrigues C., Mendes R., Baptista PV, Fernandes A.R. Targeting Tumor Microenvironment for Cancer Therapy. Int. J. Mol. Sci. 2019; 20 (4): 840. https://doi. org/10.3390/ijms20040840
  8. Bronkhorst I.H.G., Jager M.J. Uveal Melanoma: The Inflammatory Microenvironment. J. Innate Immun. 2012; 4: 454-62. https:// doi.org/10.1159/000334576
  9. Diaz-Montero C. M., Finke J., Montero A.J. Myeloid-derived suppressor cells in cancer: therapeutic, predictive, and prognostic. Semin Oncol. 2014; 41 (2): 174-84. https:// doi.org/10.1053/j.seminoncol.2014.02.003
  10. Balch C., Riley L., Bae T, Salmeron M.A., Platsoucas C.D., von Eschenbach A., Itoh K. Patterns of human tumor infiltrating lymphocytes in 120 human cancers. Arch. Surg. 1990; 125 (2): 200-5.
  11. Yang J., Li X., Liu X., Liu Y. The role of tumor-associated macrophages in breast carcinoma invasion and metastasis. Int. J. Clin. Exp. Pathol. 2015; 8 (6): 6656-64.
  12. Lagouros E., Salomao D., Thorland E., Hodge D.O., Vile R., Pulido J.S: Infiltrative T regulatory cells in enucleated uveal melanomas. Trans. Am. Ophthalmol. Soc. 2009; 107: 223-8.
  13. Schmittel A., Bechrakis N.E., Martus P, Mutlu D., Scheibenbogen C., Bornfeld N., Foerster M.H., Thiel E., Keilholz U. Independent prognostic factors for distant metastases and survival in patients with primary uveal melanoma. Eur. J. Cancer. 2004; 40: 2389-95. https://doi.org/10.10Wj. ejca.2004.06.028
  14. Ribatti D., Crivellato E., Roccaro A.M., Ria R., Vacca A. Mast cell contribution to angiogenesis related to tumour progression. Clin Exp Allergy. 2004; 34 (11): 1660-4. https://doi.org/ 10.1111/j.1365-2222.2004.02104.x
  15. Gabrilovich D.I., Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol. 2009; 9 (3): 162-74. https://doi.org/10.1038/ nri2506
  16. Coussens L.M., Werb Z. Inflammation and cancer. Nature. 2002; 420 (6917): 860-7
  17. Carretero R., Sektioglu I.M., Garbi N., Salgado O.C., Beckhove P, Hammerling G.J. Granulocytes: Eosinophils enable the antitumour T cell response. Nature Immunol. 2015; 16 (6): 609-17. https://doi. org/10.1038/ni.3159. Epub 2015 Apr 27
  18. Быков В.Л. Цитология и общая гистология. Функциональная морфология клеток и тканей человека. Учеб. для ст. мед. инст. С-Пб.: Сотис; 2002; 520
  19. Мнихович М.В. Экстрацеллюлярный матрикс, ангиогенез и клеточное микроокружение при дисгормональных гиперплазиях, фиброаденомах и раке молочной железы (световое и электронно-микроскопическое исследование). Российский медико-биологический вестник им. акад. И.П. Павлова. 2010; 1: 30-7

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