Kharkhalis I. Features of diagnosis of carcinomas of the colorectal phenotype with different metastatic potential

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0824U001444

Applicant for

Specialization

  • 222 - Медицина

23-05-2024

Specialized Academic Board

ДФ 61.051.138

Uzhhorod National University State Higher Educational Institution

Essay

The dissertation is concentrated on enhancing the diagnosis of primary colon cancer characterized by a colorectal phenotype [CK20+, CK7-, CDX-2+]. Special emphasis is placed on identifying instances of tumors exhibiting abnormal expression of markers such as β-catenin, cyclin D1, p53, EGFR (Epidermal growth factor receptor), MUC-2, and EMA, determined through immunohistochemical methods. The study is aimed to discern statistically significant differences in cases of primary CRC, considering typical and aberrant marker expression across various factors like age, patient gender, tumor location, histological tumor variant, Grade of differentiation, metastatic potential, and proliferative activity. The importance of peritumoral budding for the prognosis of aggressive behavior and high metastatic potential of the examined samples of colorectal carcinomas was determined separately. The work evaluated the diagnostic and prognostic value of indicators of intratumoral vascularization. For the first time, such objective parameters as "number", "area", "perimeter" of blood vessels were calculated and presented based on the expression of the CD34 marker in the endothelium of vessels in primary colon carcinomas of the colorectal phenotype [CK20+, CK7-, CDX-2+] using processing digital images of vessels and morphometric study in the platform Fiji were determined. Their predictive values for such indicators as the age, sex of the patient, localization of the tumor, histological type of the tumor, presence of metastases, Grade of colorectal carcinomas were clarified. There were obtained new data regarding the objective calculation of the "quantity", "area," and "perimeter" of CD34-positive vessels, as well as the background expression of markers Ki-67, β-catenin, cyclin D1, p53, EGFR, MUC- 2, EMA in the non-neoplastic tissue of the negative margins of the resection of primary colon carcinomas. Studies of aberrant expression variants of markers β-catenin, cyclin D1, p53, EGFR, MUC-2, EMA in primary colon carcinomas with a colorectal phenotype [CK20+, CK7-, CDX-2+] are gained further development, of which for the first time an aberrant type of MUC-2 mucin expression (cytoplasmic granular staining with a dot-like nuclear component) was described. Scientific ideas about gender, age, morphometric and immunohistochemical features of different histological types of primary intestinal carcinomas of the colorectal phenotype have been deepened.

Research papers

1. Хархаліс І. К., Пославська О. В. Комп'ютеризоване кількісне оцінювання внутрішньопухлинної васкуляризації і проліферації колоректальних карцином: морфометричне дослідження. Медична інформатика та інженерія. 2022. № 3 (59). С. 42-49.

2. Хархаліс І. К., Шпонька І. С., Пославська О. В. Дослідження експресії кишкового муцину MUC-2 та маркеру проліферативної активності Кі-67 в колоректальних карциномах. Морфологія. 2022. Т. 16, № 3. С. 110-117.

3. Хархаліс І. К., Шпонька І. С., Пославська О. В. Оцінка експресії маркерів β-catenin та cyclin D1 в залежності від клініко-морфологічних характеристик та проліферативної активності колоректальних карцином. Морфологія. 2022. Т. 16, № 4. С. 32-40.

4. Шпонька І. С., Хархаліс І. К., Пославська О. В. Дослідження експресії онкопротеїну р53, EGFR у колоректальних карциномах з різною проліферативною активністю. Медичні перспективи. 2023. Т. 28, № 1. С. 4-12.

5. Шпонька І. С., Пославська О. В., Хархаліс І. К., Шинкаренко Т. В. Патоморфологічний аналіз брунькування в колоректальних карциномах. Патологія. 2023. Т. 20 (2). С. 135-140.

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