Diagnosing atypia of undetermined significance in thyroid fine needle aspiration samples using nuclear scoring

WOS: 000483427400017PubMed: 31233903Background Atypia of undetermined significance (AUS) is an indeterminate category in the Bethesda system for reporting thyroid cytopathology. Cytological features described as atypia are not always observed in every case, and it is difficult to determine how the small population of cells with enlarged nuclei, a few grooves, and rare elongated nuclei should be classified. Therefore, there is inter-intra observer variability considering these cell types, even though the cytological criteria are well defined. Therefore, this study aimed to establish a nuclear scoring system to help in the differential diagnosis of AUS. Methods: Fine needle aspiration (FNA) samples that showed AUS and had surgical follow-up were included in this study. The aspirate was scored for the presence of intanuclear cytoplasmic inclusions, nuclear grooves, overlapping, enlargement, and elongation individually. The total nuclear score for each case was calculated. Statistical analysis of the association between each nuclear feature and the presence of papillary thyroid cancer (PTC) in the surgical specimens was performed. Cut-off points from the total score of these nuclear features were also calculated. Results: Nuclear grooves and overlapping were more common in malignant cases (p = 5.5 for the total score was sensitive and specific for defining malignancy. Conclusion: The risk of PTC was higher in nodules with more prominent nuclear overlapping or nuclear groove in their FNA samples. In order to achieve a more confident AUS diagnosis, our scoring system can be helpful for thyroid FNA samples

Hypoxia inducible factors and hypoxia associated factor expression profiles and prognostic significance in renal cell carcinomas

Hypoxia Inducible Factor-1 alpha and Hypoxia Inducible Factor-2 alpha (HIF-1α and HIF-2α) are crucial in Renal Cell Carcinoma (RCC) formation. Hypoxia Associated Factor (HAF) prompts HIF-1α degradation regardless of oxygen levels, but no such link exists for HIF-2α. This study encompassed 239 cases, where tissue microarray (TMA) sections were exposed to HIF-1α, HIF-2α, and HAF antibodies. Staining intensity and tumor cell percentage determined scores for HIF-1α, HIF-2α, and HAF, with median histoscore establishing "high" or "low" cutoffs. Among the cases, 64.9% (155 cases) were negative for HIF-1α, 17.6% (42 cases) displayed low, and another 17.6% (42 cases) showed strong HIF-1α expression. HIF-1α expression correlated significantly with histological type and World Health Organization/International Society of Urological Pathology (WHO/ISUP) nuclear grade. Regarding HIF-2α, 15.5% (37 cases) were negative, 23.4% (56 cases) exhibited low, and 61.1% (146 cases) displayed high expression, with larger tumor size in the high HIF-2α group. Among 239 cases, 41.4% (99 cases) were negative for HAF, 36.8% (88 cases) showed low, and 21.8% (52 cases) displayed high HAF scores. HAF expression correlated with WHO/ISUP nuclear grade and metastasis presence. Notably, HIF-2α staining intensity directly correlated with increased HAF intensity (rho=0.146; p=0.024), while HIF-1α intensity decrease corresponded with heightened HAF intensity, showing a statistically significant negative correlation (rho=-0.180; p=0.005). In this rare examination of tumor tissue, a reverse connection between HIF-1α and HAF expression was uncovered, while a linear link emerged between HIF-2α and HAF expression. Overall, this study established that HIF-1α, HIF-2α, and HAF expression are associated with an unfavorable prognosis. [Med-Science 2023; 12(3.000): 915-21

Autologous stem cell-derived chondrocyte implantation with bio-targeted microspheres for the treatment of osteochondral defects

simsek, mehmet emin/0000-0002-8081-0550; asik, Mehmet/0000-0001-9154-2697WOS: 000501331300004PubMed: 31779662Background Chondral injury is a common problem around the world. Currently, there are several treatment strategies for these types of injuries. The possible complications and problems associated with conventional techniques lead us to investigate a minimally invasive and biotechnological alternative treatment. Combining tissue-engineering and microencapsulation technologies provide new direction for the development of biotechnological solutions. The aim of this study is to develop a minimal invasive tissue-engineering approach, using bio-targeted microspheres including autologous cells, for the treatment of the cartilage lesions. Method In this study, a total of 28 sheeps of Akkaraman breed were randomly assigned to one of the following groups: control (group 1), microfracture (group 2), scaffold (group 3), and microsphere (group 4). Microspheres and scaffold group animals underwent adipose tissue collection prior to the treatment surgery. Mesenchymal cells collected from adipose tissue were differentiated into chondrocytes and encapsulated with scaffolds and microspheres. Osteochondral damage was conducted in the right knee joint of the sheep to create an animal model and all animals treated according to study groups. Results Both macroscopic and radiologic examination showed that groups 3 and 4 have resulted better compared to the control and microfracture groups. Moreover, histologic assessments indicate hyaline-like cartilage formations in groups 3 and 4. Conclusion In conclusion, we believe that the bio-targeted microspheres can be a more effective, easier, and safer approach for cartilage tissue engineering compared to previous alternatives.Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [213M683, 213M716]The Scientific and Technological Research Council of Turkey funded this project under project numbers 213M683 and 213M716

A Preliminary Investigation on the Presence of Calcifying Nanoparticles in the Breast Tumor

Calcium phosphate is deposited in many diseases, but the molecular basis of mineralization remains largely unknown. Biomineralizied calcifications that are formed by calcium deposits are also detected in breast mammograms. Some of the detected microcalcifications are thought to be related with malignancy. Taken together, calcifying nanoparticles (CNP) may be thought as a source of malign calcifications in breast cancers. The aim of the study is to research the presence of CNP in breast tumor tissue. With this aim, the presence of CNP was investigated by culturing 16 patients' breast tumor tissue and from 2 pathologic tissues with transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Their growth was monitored by optical density (OD) at a wavelength of 650 nm. CNP couldn't be found in the analysed tissues. The presence of CNP in the breast tumor tissue was researched for the first time. We could not find CNP in the breast tumor tissue, but we think this research will open a new field of study for researchers

Prognostic significance of the programmed death ligand 1 expression in clear cell renal cell carcinoma and correlation with the tumor microenvironment and hypoxia-inducible factor expression

Abstract Background Clear cell renal cell carcinoma (ccRCC) is the most common renal malignancy. Hypoxia-inducible factors, HIF-1α and HIF-2α, are expressed in the majority of ccRCC. Targeting immune checkpoints with the blockade of PD-1 and its ligand PD-L1 reorganizes T-cell activity in tumor microenvironment and provides important antitumor responses. PD-L1 upregulation has been found to be hypoxia-inducible factor (HIF) dependent. Our aim is to demonstrate the association between PD-L1 and HIF expression and to reveal the role of PD-L1 in prognosis and its association with tumor microenvironment. Methods Surgical specimens from 145 patients diagnosed with ccRCC, who had undergone radical or partial nephrectomy, were retrospectively analyzed. Immunohistochemistry on tissue microarrays (TMA) was performed to demonstrate expressions of PD-L1, HIF-1α, and HIF-2α in tumor cells and PD-1, CD4, and CD8 in lymphocytes to assess lymphocyte density in tumor microenvironment. Results PD-L1 tumor cell expression was detected in 20/125 (13.8%) cases, which correlated with higher levels of PD-1, CD4, CD8 and HIF-2α expression. Low or high expression of HIF-1α was similar in PD-L1-positive cases. When PD-L1-positive cases were compared with negative ones, there was no significant difference in terms of prognostic factors. However, the number of WHO/ISUP grade 3–4 tumors was significantly higher in PD-L1-positive cases than in negative ones. Conclusion PD-L1 tumor cell expression is strongly associated with increased HIF-2α expression and presence of dense lymphocytic infiltration in ccRCCs. Our findings confirm that PD-L1 positivity is associated with high ISUP nucleolar grade. The association between PD-L1, HIF, and lymphocyte density in tumor microenvironment must be clarified and especially taken into account in combination treatment