Lazaruk O. Prognosis of metastases of ductal breast cancer following the pathomorphological characteristics of the tumour and tissues around the tumour

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0419U001508

Applicant for

Specialization

  • 14.03.02 - Патологічна анатомія

26-06-2019

Specialized Academic Board

Д 64.600.03

Essay

The material for the thesis was obtained in patients who were on inpatient treatment at the Chernivtsi Regional Clinical Oncology Center with the diagnosis of invasive ductal breast carcinoma. The histological study of the material allowed to distribute all observations by TNM classification categories. 162 observations with invasive ductal breast carcinoma were investigated. The category (N) was divided into 2 groups: without metastases - 40.12% (n= 65), and the group with metastases - 59.88% (n = 97). Histologic, histochemical and immunohistochemical methods of investigation were used to achieve the goal. The metastases criteria of prognosis set the average results between metastatic groups and without them for each individual study. The reliability of the results was verified through the use of medical statistics programs. High results were obtained with the use of histochemical methods for investigating the properties of proteins. For the purpose of predicting the cancerous metastases were used the limit proteolysis of proteins, the method of dyeing in tumour cells and connective tissue fibers (zone I) by determining the free NH2 group of proteins by A. Yasuma and T. Ichikava in ( relative optical density unit). According to the results of tumour cells and connective tissue fibers (zone I) a parenchymal-stromal coefficient was established, which was defined as the prognostic criterion and was "1". For the free NH2 group of proteins the result of the metastases monitoring group is higher than the indicator of the prognostic criterion (91.8%) and 9.2% of the group without metastases. The results of the procedure were evaluated using computer micro densitometry. To study the "acid" and "main" groups of proteins bromophenol blue stained with Mikel Calvo was used. The difference of indicators was determined by the coefficient R/B with the use of computer microspectrometry analysis. The prognostic criterion for tumour cells was coefficient R/B ratio of 1.34, and for connective tissue fibers (zone I) - "1.64". In the group with metastases, compared to tumour cells, the result was higher in 92.8% compared to 6.2% in the group without metastases. In connective tissue fibers of zone I in the group of observations with metastases the result is higher - 91.8% and 7.7% in the group without metastases. Due to the high variability and low difference in the expression of estrogen, progesterone, HER2/neu between groups with metastases and without them it was not possible to determine the metastases prognosis criterion. But their results do not affect the value of use for predicting tumour progression. The results of immunohistochemical research methods (ki-67, p53, bcl-2, metalloproteinase-2, metalloproteinase-9, vimentin, Willebrand factor) are statistically reliable. The evaluation of the expression results was performed on the number of positively colored cells. For p53, bcl-2, the prediction criterion is 15%, and for ki-67 - 10% of positively colored cells. The results for metalloproteinase-2, metalloproteinase-9, vimentin and Willebrand factor were counted using computer microdensitometry in (relative optical density unit). Interpretation of the results of histochemical and immunohistochemical studies in order to rank for informativity and determine the sensitivity and specificity of methods used statistical methods of research - the definition of risk ratio and odds ratio. The best predictions of metastases according to the definition of risk ratio (RR) and odds ratio (OR) were the results of the definition of "acid" and "main" protein groups and limited proteolysis of proteins. By the diagnostic value of the study of "acid" and "main" groups of proteins for tumour cells, the R/B ratio was 1.34, RR - 9.30, OR - 196.07; in connective tissue fibers with the diagnostic value 1.64 - RR - 8.05, OR - 133.50. Limited proteolysis was studied using microdensitometry on dye-colored samples with Ninhydrin-Schiff reaction. When summing up the results in tumour structures, the result for the parenchymal-stromal coefficient RR is 7.85, OR - 109.40. Immunohistochemical technique with the highest relative risk is vimentin. The presence of Vimentin in tumour cells speaks of changes in the epithelial cell towards the mesenchymal cells. The results can be used to improve morphological diagnosis and new approaches to the treatment of invasive ductal breast carcinoma.

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