In the dissertation work in order to improve the biopsy diagnosis of undif-ferentiated (anaplastic) tumors and tumor metastases from an unknown primary source, the morphometric characteristics of "area", "perimeter" and "roundness co-efficient" were investigated by processing digital micrographs of tumors of epithe-lial, mesenchymal, melanocyte and hemolymphocyte origin in the ImageJ program with subsequent determination of the limits of morphometric values for such cate-gories of tumors as "small cell", "medium cell", "large cell" and separately for "small-round-blue-cells" tumors, compared with the size of normal lymphocytes; among the histopathological diagnoses of archival material retrospectively deter-mined the percentage of categories of carcinoma verification of unknown primary localization to understand the effectiveness of an interdisciplinary approach in the diagnosis of tumors from an unknown source; immunohistochemical and morpho-metric characteristics for verification of favorable immunophenotypes of clinical and morphological syndrome "Cancer of unknown primary site" are formed; ob-servations of favorable phenotypes of the clinical and morphological syndrome "Cancer of unknown primary site" with the presence of amplification of the ERBB2 gene and separate deletion of the 9p21 locus of the CDKN2A gene by FISH method and compared with the corresponding change in HER-2/neu and р16ІNK4A protein expression were investigated by the IHC method.
Scientific novelty. For the first time, objective diagnostic ranges of MPM parameters of area, perimeter and roundness coefficient of nuclei were determined for "small cell tumors", "medium cell tumors", "large cell tumors" and separately for "small-round-blue-cell tumors" compared with the size of normal lymphocytes in the digital image processing program ImageJ. New data were obtained on the objective parameters "area", "perimeter" and "roundness coefficient" of cell nuclei of metastatic tumors of different histogenesis, verified by IHC. The only source of serous papillary carcinomatosis in women with immunophenotype [СК 7 (+), СА-125 (+), СК 20 (-), ER (+), РАХ-8 (+), WT-1 (+), р16ІNK4A (+), р53 (+)] and se-rous AC of the ovary of the “high-grade” variant from the distal fragments of the fallopian tube was confirmed, which allows to exclude it from the clinical and morphological syndrome "Cancer of unknown primary site". Extended scientific understanding of age, gender, histological, IHC and MPM features of favorable immunophenotypes of clinical and morphological syndrome " Cancer of unknown primary site " to understand the unique biology of primary disseminated carcino-mas, compared with locally distributed ones. Studies on the correspondence of changes in epidermal growth factor HER-2/neu expression to ERBB2 gene ampli-fication and p16INK4A oncoprotein expression to deletion of the 9p21 locus of the CDKN2A gene in metastatic CUP have been further developed.
Practical meaning. To improve the quality and speed of verification of undif-ferentiated (anaplastic) tumors and tumor metastases from unknown primary sources, a diagnostic algorithm was optimized: it was proposed to perform IHC at the stage of analysis of sections stained with hematoxylin and eosin, using digital MPM using the ImageJ program. When determining the values of MPM parameters of "small-round-blue-cell tumors" (30 - 45 μm2 in area, 25 - 35 μm in perimeter and 0.75 - 0.90 in roundness) it is recommended to change the standard primary IHC panel [Рan СК АЕ1/3, Vimentin, CD45, S100 and/or HMB45] to [Рan СК АЕ1/3, Desmin, CD45, CD56, CD99, S100 and/or HMB45], which immediately covers most nosological units of this category of tumors. IHC and MPM character-istics of nine favorable immunophenotypes of the CUP syndrome, according to which they can be treated as potentially curable disseminated forms of CUP, have been elucidated. The greater accuracy of the FISH method in the diagnosis of 9p21 / CDKN2A deletion and ERBB2 amplification has been proved, compared with the iHC method, which determines them not directly but through the products of nu-clear cytoplasmic expression of p16INK4A and membrane overexpression of HER-2/neu, respectively. According to the results of the research, the share of metastatic tumors of the third category of verification "confirmed CUP" significantly exceeds the world indicators (21.95% vs. 3-5%), which raises the practical issue of inter-disciplinary communication and quality of patient examination at the "pre-biopsy stage". Ukraine's patent № 111478 for a utility model and an information letter № 68-2019 on innovations in the health care system for the development of "Method for predicting metastases of squamous cell carcinoma of the larynx." were ob-tained.
