Chyzhma R. Pathomorphological characteristics of biomineralization in malignant ovarian tumors

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0824U001635

Applicant for

Specialization

  • 222 - Медицина

02-05-2024

Specialized Academic Board

5030

Sumy State University

Essay

The increase in morbidity and mortality rates for malignant tumors of the female reproductive system is an urgent problem today. Among malignant tumors of the female reproductive system, ovarian cancer ranks fourth after neoplasms of the breast, body, and cervix. Although ovarian cancer has a lower prevalence rate compared to breast cancer, the mortality rate for this pathology is three times higher. The high mortality rate in malignant ovarian tumors is due to the asymptomatic course, the progression of the tumor process, and the ineffectiveness of screening diagnostic methods. It should also be noted that the results of ovarian cancer treatment depend on many factors, namely the stage of the disease, the type of tumor process, histogenesis, and the degree of differentiation. Thus, this again proves the value of early diagnosis of malignant neoplasms of the ovaries. The dissertation work is devoted to an actual problem, namely improving the possibilities of early diagnosis and forecasting the course of malignant ovarian tumors against the background of pathological biomineralization processes. The following research methods were used to solve this problem, analyze and substantiate the obtained results: histological, histochemical, immunohistochemical, physicochemical (scanning and transmission electron microscopy, energy dispersive X-ray spectroscopy, fluorescence microscopy and chemical analysis), morphometric and instrumental diagnostic methods (ultrasound diagnostics), statistical processing of data using parametric and non-parametric criteria. A thorough analysis of the epidemiological characteristics of ovarian cancer both in Ukraine and in the Sumy region for 2014-2021 was carried out, which made it possible to establish the level of morbidity and mortality in the Sumy region in comparison with national indicators to describe the age analysis of the incidence, to analyze the distribution of histological types and to conduct a study regarding the staging of the tumor process. In the course of the study, it was established that the development of biomineralization begins at the early stages of carcinogenesis, which can be important in the early diagnosis of ovarian tumors. Biominerals larger than 200 μm are visualized using ultrasound. The analysis of histological examination images demonstrated the presence of pathological biominerals in the form of psammoma bodies (PT) in the tumor tissue of the ovary with a variation in the amount from 1 to 200 units. Analysis of the morphometric characteristics of minerals based on the images of histological and immunohistochemical research methods showed size fluctuations from 12.6 to 493.7 μm. By their structure, biominerals consist of lamellae and an interlamellar layer located sequentially. A complex histochemical study of the samples (staining with alizarin red S, according to the von Koss method, PAS-reaction, and Van Gieson) made it possible to visualize the presence of calcium phosphate compounds as the mineral basis of all the studied biomineral particles and the presence of glycoproteins, phospholipids, and glycosaminoglycans. In the immunohistochemical study, significantly higher expression of OPN (p < 0.001), SPARC (p < 0.01), and Casp3 (p < 0.05) markers were found in the samples of the ovarian cancer group with pathological biomineralization. No significant difference was obtained by the Student's test between the first and second studied groups when using antibodies against OPG and RANKL. Also, no significant difference was established between the studied groups when using antibodies against CD68 and CD163. Scanning electron microscopy (SEM) established that the calcifications are particles of different sizes, round in shape, with the visualization of lamellar structures, the so-called layering. In the study of mineralized ovarian cancer tissue using X-ray diffraction and transmission electron microscopy with electron diffraction, traces of the presence of the calcite phase were established, which was not previously reported. Since biominerals are formed in the early stages of carcinogenesis, this will allow the detection of malignant neoplasms of the ovaries in the initial stages of development. This, in turn, confirms the possibility of using diagnostic instrumental methods with high resolution for early diagnosis of ovarian cancer. Therefore, this method of optimizing the diagnosis of malignant neoplasms of the ovaries is based on the structural properties of biomineral deposits of tumor tissue, which will allow for increasing the accuracy of early diagnosis, as well as the informativeness of the final result at the preoperative and postoperative stages, which can not only improve the prognosis but also preserve the quality of life female patients.

Research papers

1. Чижма Р.А., Біденко М.В., Николенко А.П., Піддубний А.М., Москаленко Р. А. Патологічна біомінералізація при пухлинах яєчників. Вісник проблем біології і медицини, 2020. № 4(158). С. 43-48.

2. Чижма Р.А., Николенко А.П., Піддубний А.М., Москаленко Р.А. Аналіз захворюваності на злоякісні пухлини яєчників у Cумській області в 2014–2018 рр. Морфологія? 2021. № 15(1). С. 73-78.

3. Chyzhma R., Piddubnyi A., Danilchenko S., Kravtsova O., Moskalenko R. Potential Role of Hydroxyapatite Nanocrystalline for Early Diagnostics of Ovarian Cancer. Diagnostics, 2021. № 11(10). 1741.

4. Hyriavenko N., Lуndіn M., Sikora V., Chyzhma R., Lуndіna Y., Sikora K., Awuah W.A., Romaniuk A. Neuroendocrine Tumor of the Fallopian Tube and Serous Adenocarcinoma of the Ovary: Multicentric Primary Tumors. Turkish Journal of Pathology, 2023. №39(2). Р. 161-166.

5. Чижма Р.А., Москаленко Р.А. Імуногістохімічне дослідження раку яєчників з патологічною біомінералізацією. Одеський медичний журнал, 2023 № 4(185). С. 35-40

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