Medullary Thyroid Carcinoma (MTC) constitutes around 5% of all thyroid cancers. Trace elements assessment has emerged as a useful strategy in the diagnostics of MTC combined with Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Matrix Metalloproteinases (TIMPs) analysis. The aim of this study was to compare the presence and content of trace elements (i.e., Copper (Cu), Zinc (Zn), Iron (Fe), and Manganese (Mn)) in MTC with respect to control samples and their potential relationship with markers of MTC in tissues. The study included 26 patients who had undergone thyroidectomy, due to the diagnosis of MTC and 17 patients as control. We combined tumour pathology and staging, immunohistochemical analysis of calcitonin, MMPs, and TIMPs, with analytical biochemistry using Inductively Coupled Plasma – Mass Spectrometry (ICP-MS) to determine the levels of trace elements. No differences by MTC type for MMPs and their TIPMs, although strong TIMP-1 and TIMP-2 immunohistochemical expression of MTC were unveiled. Additionally, Zn, Fe, and Mn tended to be decreased, and Cu to be increased in samples presenting MTC with respect to controls. Moreover, Zn was the unique trace element which seemed to be correlated with MMPs and TIMPs. Trace elements such as Zn, Fe, and Mn are decreased in tissues affected by MTC. In addition, Zn may be the trace element which saves more relationship with the proportion and intensity of MMPs, being considered altogether useful biomarkers of MTC. We therefore suggest the analysis of novel and traditional markers of MTC as a novel approach in this pathology.

Thyroid carcinomas are growing malignancies worldwide. They encompass several diagnostic categories with varying degrees of dedifferentiation. Focal adhesion kinase is involved in cellular communication and locomotion. It is regulated on a posttranscriptional level by miR-7, miR-135a, and miR-138 and on a posttranslational level by autophosphorylation at Y397 (pY397-FAK). We related regulators of FAK with histologic dedifferentiation, clinicopathological factors, and differential diagnosis in the thyroid neoplasia spectrum. We classified 82 cases into 5 groups with increasing aggressiveness: healthy tissue, follicular and classical variants of papillary thyroid carcinoma (PTC), dedifferentiated PTC, and anaplastic carcinoma. MiRs were analyzed by RT-qPCR. Protein expression of pY397-FAK was analyzed by immunohistochemistry (separately in the membrane, cytoplasm, and nuclear compartment) and Western blot. All three miRs were upregulated in healthy tissue compared to malignant, while pY397-FAK was downregulated. MiRs and pY397-FAK were not mutually correlated. MiR-135a-5p was decreasing while membranous and cytoplasmic pY397-FAK increased with dedifferentiation. Neither miR correlated with clinicopathological factors. MiR-135a-5p, miR-138-5p, and membranous and cytoplasmic pY397-FAK discriminated the follicular from the classical variant of PTC. Disturbances of FAK regulation on different levels contribute to neoplastic dedifferentiation. pY397-FAK exerts its oncogenic role in the membrane and cytoplasm. Diagnostically, miRs-135a-5p, miR-138-5p, and membranous and cytoplasmic pY397-FAK differentiated between classical and follicular PTC.

A challenging task in routine practice is finding the distinction between benign and malignant paragangliomas and pheochromocytomas. The aim of this study is to conduct a comparative analysis of angiogenesis by assessing intratumoral microvascular density (MVD) with immunohistochemical (IHC) markers (CD31, CD34, CD105, ERG), and S100 immunoreactivity, Ki67 proliferative index, succinate dehydrogenase B (SDHB) expressiveness, tumor size with one the most utilized score Pheochromocytoma of Adrenal Gland Scales Score (PASS), using tissue microarray (TMA) with 115 tumor samples, 61 benign (PASS < 4) and 54 potentially malignant (PASS ≥ 4). We found no notable difference between intratumoral MVD and potentially malignant behavior. The group of potentially malignant tumors is significantly larger in size, has lower intratumoral MVD, and a decreased number of S100 labeled sustentacular cells. Both groups have low proliferative activity (mean Ki67 is 1.02 and 1.22, respectively). Most tumors maintain SDHB expression, only 6 cases (5.2%) showed a loss of expression (4 of them in PASS < 4 group and 2 in PASS ≥ 4). PASS score is easily available for assessment and complemented with markers of biological behavior to complete the risk stratification algorithm. Size is directly related to PASS score and malignancy. Intratumoral MVD is extensively developed but it is not crucial in evaluating the malignant potential.

Objective: The aim of this study was to evaluate the relationship between the immunohistochemical score of cell proliferation index Ki-67 and steroid receptors in patients with a pathohistological diagnosis of breast cancer. The impact of neoadjuvant therapy on biological markers in breast cancer remains controversial. Methods: All patients with invasive breast cancer, as the primary and only malignancy, who underwent surgical and neoadjuvant therapy at the Institute of Oncology and Radiology of the Republic of Serbia (IORS) between 2017 and 2019 were included in the retrospective study. The expression level of Ki-67 and steroid receptors was detected by immunohistochemical analysis. Data were collected in an Excel database and analyzed in the statistical software SPSS program version 25. For statistical data processing Chi-squared test, KruskalWallis test, and Mann-Whitney U test were used. For all statistical analyses, a p <0.05 was considered statistically significant and a p≤0.001 was considered highly statistically significant. Results: The study included 190 patients with invasive breast cancer. The mean age of all patients at diagnosis was 57.2 ± 11.8 years. Among the patients, 64.2% are postmenopausal, 33.7% perimenopausal and 2.1% menopausal. There is a significant inverse correlation between the value of Ki-67 and the expression of steroid receptors. Conclusion: Ki-67 is an important biomarker in clinical practice for determining prognosis, residual risk, and response, and evaluating the effectiveness of neoadjuvant therapy. The results of our study revealed a correlation between high Ki-67 cell proliferative index values and lower steroid receptor expression values.

A Challenging task in routine practice is finding distinction between benign and malignant paragangliomas and pheochromocytomas. The aim of this study is a comparative analysis of angiogenesis by assessing intratumoral microvascular density (MVD) with immunohistochemical (IHC) markers (CD31, CD34, CD105, ERG), and S100 immunoreactivity, Ki67 proliferative index, SDHB expressiveness, tumor size with one the most utilized score Pheochromocytoma of Adrenal Gland Scales Score (PASS), using tissue microarray (TMA) with 115 tumor samples, 61 benign (PASS<4) and 54 potentially malignant (PASS ≥4). We found no notable difference between intratumoral MVD and potentially malignant behavior. Group of potentially malignant tumors are significantly larger in size, have lower intratumoral MVD, and decreased number of S100 labeled sustentacular cells. Both groups have low proliferative activity (mean Ki67 is 1,02 and 1,22 respectively). Most tumors maintains SDHB expression, only 6 cases (5,2%) showed a loss of expression (4 of them in PASS<4 group and 2 in PASS≥4). PASS score is easy available for assessment, and complemented with markers of biological behavior completes risk stratification algorithm. Size is directly related with PASS score and malignancy. Intratumoral MVD is extensively developed but it is not crucial in evaluating the malignant potential.

One hundred years after its establishment, the Institute of Pathology "Prof. Dr. Đorđe Joannnović" remains the leading institution in Serbia and the region, where besides educating students and laboratory technicians, various state-of-the-art diagnostic procedures in the fields of histopathology, autopsy, and molecular pathology are conducted. The Department of General Pathology and Pathological Anatomy was also founded in 1922. Dr Đorđe Joannnović was the first full professor and the head of the department. After World War II, a joint department of four subjects was formed. An independent Department of Pathological Anatomy was reestablished in 1978, with academician Prof. Vladimir Kanjuh as the first head of the newly formed department. Teaching at the Department of Pathology has been conducted according to a new program since the academic year 2006/07 academic year. Since its beginings, the Department of Pathology has supported students' scientific research work and has been involved in facilitating professional and scientific international student exchange. Teaching of basic academic medical studies in English at the Department of Pathology has been ongoing since 1997. Within the department, there are specializations in Clinical Pathology and Medical Cytology, and in the academic year 2022/23 academic, the first generation of students in the "Pathological Basis of Diseases" doctoral program was enrolled. Today, the Institute of Pathology is listed among the reference institutions of the Republic of Serbia. It possesses a laboratory for routine histological processing of biopsy and autopsy material, an immunohistochemistry laboratory, and a laboratory for molecular pathology. Members of the Department and the Institute of Pathology are authors of numerous professional and scientific publications. They have been involved in founding and working within important professional, health, and scientific institutions in the country and the region. Owing to its exceptional contributions to the development of medical science and practice, the Institute of Pathology was awarded the Order of St. Sava, 3rd class, in 2017.