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Transcription factor PAX8, expressed during embryonic kidney development, has been previously detected in various kidney tumors. In order to investigate expression of PAX8 transcription factor in acute kidney injury (AKI) and chronic kidney diseases (CKD), immunohistochemical analysis was performed. Presence, location and extent of PAX8 expression were analyzed among 31 human kidney samples of AKI (25 autopsy cases, 5 kidney biopsies with unknown etiology and 1 AKI with confirmed myoglobin cast nephropathy), as well as in animals with induced postischemic AKI. Additionally, expression pattern was analyzed in 20 kidney biopsy samples of CKD. Our study demonstrates that various kidney diseases with chronic disease course that results in the formation of tubular atrophy and interstitial fibrosis, lead to PAX8 expression in the nuclei of proximal tubules. Furthermore, patients with PAX8 detected within the damaged proximal tubuli would be carefully monitored, since deterioration in kidney function was observed during follow-up. We also showed that myoglobin provoked acute kidney injury followed with large extent of renal damage, was associated with strong nuclear expression of PAX8 in proximal tubular cells. These results were supported and followed by data obtained in experimental model of induced postischemic acute kidney injury. Considering these findings, we can assume that PAX8 protein might be involved in regeneration process and recovery after acute kidney injury. Thus, accordingly, all investigation concerning PAX8 immunolabeling should be performed on biopsy samples of the living individuals. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is the deadliest urological neoplasm. Up to date, no validated biomarkers are included in clinical guidelines for the screening and follow up of patients suffering from RCC. Slug (Snail2) and Snail (Snail1) belong to the Snail superfamily of zinc finger transcriptional factors that take part in the epithelial–mesenchymal transition, a process important during embryogenesis but also involved in tumor progression. We examined Slug and Snail immunohistochemical expression in patients with different stages of renal cell carcinomas with the aim to investigate their potential role as staging and prognostic factors. A total of 166 samples of malignant renal cell neoplasms were analyzed using tissue microarray and immunohistochemistry. Slug and Snail expressions were evaluated qualitatively (presence or absence), in nuclear and cytoplasmic cell compartments and compared in relation to clinical parameters. The Kaplan–Meier survival analysis showed the impact of the sarcomatoid component and Slug expression on the survival longevity. Cox regression analysis separated Slug as the only independent prognostic factor (p = 0.046). The expression of Snail was associated with higher stages of the disease (p = 0.004), especially observing nuclear Snail expression (p < 0.001). All of the tumors that had metastasized showed nuclear immunoreactivity (p < 0.001). In clear cell RCC, we showed a significant relationship between a high nuclear grade and nuclear Snail expression (p = 0.039). Our results suggest that Slug and Snail could be useful immunohistochemical markers for staging and prognosis in patients suffering from various RCCs, representing potential targets for further therapy strategies of renal cancer. [ABSTRACT FROM AUTHOR]

The precise differentiation of renal cell tumors (RCTs) is sometimes hard to achieve using standard imaging and histopathological methods, especially for those with eosinophilic features. It has been suggested that the vast overabundance of mitochondria, as a well-known hallmark of eosinophilic cytoplasm, and could be a characteristic of distinct tumor types with opposing clinical outcomes. Thus, we intended to explore the associations between mitochondrial distribution patterns in different RCTs, including 43 cell renal cell carcinomas (ccRCCs), 15 papillary renal cell carcinomas (pRCCs), 20 chromophobe renal cell carcinomas (chRCCs), and 18 renal oncocytomas (ROs). Tumor samples were stained with two anti-mitochondrial antibodies (mitochondrial antibody Ab-2, clone MTC02; prohibitin, II-14-10, MA5-12858), applying immunohistochemistry and immunofluorescence to define mitochondrial distribution patterns (coarse scanty, moderate granular, and diffuse granular). Our results revealed significantly different expression patterns among the investigated RCTs (p < 0.001). The majority of ccRCCs exhibited coarse scanty mitochondrial staining, while all chRCCs had moderate granular expression. Nevertheless, all ROs, all pRCCs, and two cases of ccRCC presenting with higher nuclear grade and eosinophilic cytoplasm had diffuse granular mitochondrial expression. Moreover, with increased distribution of mitochondria, the intensity of staining was higher (p < 0.001). Here we present a strategy that utilizes fast and easy mitochondrial detection to differentiate RO from chRCC, as well as other eosinophilic variants of RCC with high accuracy. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate cell and biochemical biomarkers and establish their prognostic value in patients with advanced laryngeal cancer. Material and Methods: A prospective study included 52 patients with advanced laryngeal carcinoma surgically treated at the tertiary referral center. Tumor tissue was immunohistochemically stained for T-cell markers (CD4 and CD8), and levels of cytokines (IL-6 and IL-8) and C-reactive protein were analyzed from blood samples. Results: Overall 3-year survival (OS) of patients included in the study was 69.2% and the disease specific survival (DSS) 72.5%. Higher expression of CD4+ and CD8+ were significant prognostic factors with positive impact on both OS and DSS in univariate analysis, but not in multivariate analysis. Levels of IL-8 were a significant predictor of 3-year OS and DSS survival in patients with advanced laryngeal cancer but not levels of IL-6 and CRP values. Conclusion: Though high expression of CD4 and CD8 were demonstrated in the tumor tissue, but their prognostic role was not established. Higher values of IL-8 proved to be significant negative predictor of DSS. This could further collaborate the inclusion of combination of biomarkers in assessment of favorable treatment choice in patients with advanced laryngeal carcinoma. [ABSTRACT FROM AUTHOR]