Publications by authors named "M Gachechiladze"

40 Publications

HISTOPATHOLOGICAL, PROLIFERATIVE, APOPTOTIC AND HORMONAL CHARACTERISTICS OF VARIOUS TYPES OF LEIOMYOMAS.

Georgian Med News 2021 Mar(312):119-125

Tbilisi State Medical University, Georgia.

Uterine leiomyomas decrease the quality of life by causing significant morbidity among women of reproductive age. Histologically various types of leiomyoma's can be differentiated. We have analysed the histopathological, proliferation, apoptotic and hormonal profile in different types of leiomyomas. Study included altogether 140 cases distributed into following groups: group I - normal myometrium (20 cases), group II-classic leiomyoma (69 cases), group III-cellular leiomyoma (15 cases), group IV - bizarre cell/atypical leiomyoma (22 cases), group V - smooth muscle tumors of uncertain malignancy potential (STUMP) (8 cases) and group VI - leiomyosarcoma (6 cases). Together with classic histopathological features such as nuclear atypia, cellularity, presence of mitoses, vasculature and necrosis, immunohistochemical phenotype using antibodies against Ki67, Cas3, ER and PR were analysed. The results of our study showed that leiomyomas are characterised with variable histopathological and immunohistochemical phenotype. Especially, two entities, bizzare/atypical leiomyoma and STUMP, which can be divided into two subgroups according to the presence of the degree of atypia and the expression of proliferation, apoptosis and hormonal markers, which might be the explanation of their different prognosis. Presented histopathological and immunohistochemical features should be considered in the diagnosis of myometrial smooth muscle tumors.
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March 2021

DISTRIBUTION OF STEM CELLS IN DIFFERENT THYROID LESIONS IN PATIENTS OF REPRODUCTIVE, MENOPAUSAL AND POST-MENOPAUSAL AGE.

Georgian Med News 2021 Mar(312):92-99

Tbilisi State Medical University.

Different studies indicate that cancer stem cells (CSCs) play an important role in the progression and therapy resistance in different cancer types. The aim of our study was to analyse the distribution of CSCs in different thyroid lesions, in reproductive, menopausal and post-menopausal women. Study included altogether 200 formalin-fixed and paraffin-embedded tissue material, with the diagnosis of NIFTP, Hashimoto's thyroiditis, papillary thyroid carcinoma (PTC) and PTC and Hashimoto's thyroiditis co-occurred cases. Normal thyroid gland was used as a control tissue. Stem cell marker - CD44, as well as other markers including Ki67, BCL2, CK19, CD56, ER were investigated with standard immunohistochemical procedure. The results of our study indicated that CD44 stem cell marker, as well as proliferation marker Ki67 is significantly upregulated in PTC cases in all age groups. However, the expression of CD44 and Ki67 is significantly higher in reproductive age patients, compared to patients in menopause and post-menopause. In addition, the expression of CD44 and Ki67 is significantly higher in PTC and Hashimoto's thyroiditis co-occurred cases, compared to cases with PTC only.
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March 2021

LC3A positive "stone like structures" are differentially associated with survival outcomes and CD68 macrophage infiltration in patients with lung adenocarcinoma and squamous cell carcinoma.

Lung Cancer 2021 Jun 15;156:129-135. Epub 2021 Apr 15.

Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine and Dentistry, Palacký University, Olomouc, Czech Republic; Faculty of Medicine, University of Ostrava, Czech Republic. Electronic address:

Aims: The aim of the study was to analyse the prognostic and predictive value of LC3A positive' 'Stone Like Structures'' (SLSs) in a large cohort of patients with non-small cell lung carcinoma (NSCLC) and to check its relationship with tumor infiltrating lymphocytes (TILs) and PD-L1 expression.

Methods: Tissue microarrays from 1015 patients diagnosed at the Institute of Pathology and Molecular Pathology, University Hospital Zurich, Switzerland, were stained for LC3A, PD-L1, CD3 and CD68 using automated tissue stainer Ventana Benchmark Ultra (Roche). TILs were assessed in matched haematoxylin and eosin stained slides.

Results: LC3A positive SLSs, were significantly associated with worse overall (OS) and disease-free survival (DFS) outcomes in patients with lung adenocarcinoma (LADC) (HR = 2.4, 95 %CI(.994-1.008, p = 0.029) and HR = 3.9, 95 %CI (1.002-1.014), p = 0.002 respectively), whilst it was associated with better OS and DFS in patients with lung squamous cell carcinoma (LUSC), with marginal significance (HR = .99, 95 %CI(.975-1.011),p = 0.042 and HR = .99, 95 %CI (.975-1.008), p = 0.026). Multivariate analysis showed that LC3A SLSs are independent poor prognostic factor only in patients with LADC. In addition, LC3A SLSs, were negatively associated with CD68 count in LADC, whilst there was a positive correlation in LSCC.

Conclusions: LC3A SLSs are differentially associated with the survival outcomes and CD68 count in LADC and LSCC. Further studies are justified for the understanding the underlying biological mechanisms of this phenomenon.
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http://dx.doi.org/10.1016/j.lungcan.2021.04.008DOI Listing
June 2021

Skp2 and Slug Are Coexpressed in Aggressive Prostate Cancer and Inhibited by Neddylation Blockade.

Int J Mol Sci 2021 Mar 11;22(6). Epub 2021 Mar 11.

Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University and University Hospital, 779 00 Olomouc, Czech Republic.

Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men in Western countries, and there is still an urgent need for a better understanding of PCa progression to inspire new treatment strategies. Skp2 is a substrate-recruiting component of the E3 ubiquitin ligase complex, whose activity is regulated through neddylation. Slug is a transcriptional repressor involved in the epithelial-to-mesenchymal transition, which may contribute to therapy resistance. Although Skp2 has previously been associated with a mesenchymal phenotype and prostate cancer progression, the relationship with Slug deserves further elucidation. We have previously shown that a high Gleason score (≥8) is associated with higher Skp2 and lower E-cadherin expression. In this study, significantly increased expression of Skp2, AR, and Slug, along with E-cadherin downregulation, was observed in primary prostate cancer in patients who already had lymph node metastases. Skp2 was slightly correlated with Slug and AR in the whole cohort (Rs 0.32 and 0.37, respectively), which was enhanced for both proteins in patients with high Gleason scores (Rs 0.56 and 0.53, respectively) and, in the case of Slug, also in patients with metastasis to lymph nodes (Rs 0.56). Coexpression of Skp2 and Slug was confirmed in prostate cancer tissues by multiplex immunohistochemistry and confocal microscopy. The same relationship between these two proteins was observed in three sets of prostate epithelial cell lines (PC3, DU145, and E2) and their mesenchymal counterparts. Chemical inhibition of Skp2, but not RNA interference, modestly decreased Slug protein in PC3 and its docetaxel-resistant subline PC3 DR12. Importantly, chemical inhibition of Skp2 by MLN4924 upregulated p27 and decreased Slug expression in PC3, PC3 DR12, and LAPC4 cells. Novel treatment strategies targeting Skp2 and Slug by the neddylation blockade may be promising in advanced prostate cancer, as recently documented for other aggressive solid tumors.
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http://dx.doi.org/10.3390/ijms22062844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000894PMC
March 2021

Comparative Analysis of Immunohistochemical Staining Intensity Determined by Light Microscopy, ImageJ and QuPath in Placental Hofbauer Cells.

Acta Histochem Cytochem 2021 Feb 20;54(1):21-29. Epub 2021 Feb 20.

Department of Histology and Embryology, Faculty of Medicine and Dentistry, Palacky University, 779 00, Olomouc, Czech Republic.

Software based analyses of immunohistochemical staining are designed for obtaining quantitative, reproducible, and objective data. However, often times only a certain type of positive cells or structures need to be quantified thus whole image analysis cannot be performed. Such an example is Hofbauer placental cells, which show positivity of some antigens together with trophoblast, but only Hofbauer cells represent the regions of interest (ROIs). Two independent observers evaluated the immunohistochemical staining intensity of Hofbauer cells in placenta samples stained for cytoplasmic antigens by ImageJ, QuPath and light microscopy. Thus, the precise manual determination of ROIs, i.e. Hofbauer cells, was necessary. We detected low inter-observer variability in staining intensity. Almost perfect agreement between observers was reached for ImageJ and QuPath whilst substantial agreement was reached for light microscopy evaluation. As for the comparison of ImageJ, QuPath and light microscopy, the agreement of all three methods (identical immunohistochemical intensity) was achieved for 38.1% samples. The almost perfect agreement of staining intensities was reached between ImageJ and QuPath, and moderate agreement for comparison of the light microscopy to both software. Software analyses are much more time-consuming, thus their utilization is at least questionable to evaluate ROIs with selection.
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http://dx.doi.org/10.1267/ahc.20-00032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947637PMC
February 2021