Browsing by Subject "Vitamin D receptor"

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    A low nuclear-to-cytoplasmic ratio of VDR expression is an independent prognostic marker in breast cancer
    (Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Schubert Charlotte; Vilsmaier Theresa; Batz Falk; Cavaillès Vincent; Sixou Sophie; Kolben Thomas; Meister Sarah; Buschmann Christina; Hagemann Friederike; Biología Celular e Histología
    The aim of this retrospective study was to analyze the prognostic value of cytoplasmic versus nuclear expression of the vitamin D receptor (VDR) in breast cancer (BC) tissue samples and to relate the results to clinicopathological parameters. VDR expression was assessed in 319 primary breast cancer patients using the Remmele and Stegner immunoreactive scoring (IRS) system. Follow-up data were obtained from the Munich Cancer Registry. The correlation with overall survival (OS) and disease-free survival (DFS) was calculated using univariate and multivariate analyses. Correlation analysis revealed a correlation between nuclear VDR expression and improved outcomes for both OS (p=0.004) and DFS (p=0.001). Conversely, cytoplasmic VDR expression was significantly associated with a shorter OS (p=0.003) and DFS (p<0.001). Additionally, both cytoplasmic and nuclear VDR expression were found to be independent markers of DFS (p<0.001; p=0.021) when examined alongside clinicopathological parameters. Moreover, nuclear VDR expression was positively associated with lower lymph node invasion (pN; p=0.01). For triple-negative patients, cytoplasmic VDR expression was found to have a significant inverse correlation with DFS (p<0.001). Lastly, the ratio of VDR nuclear/cytoplasmic was identified as an auxiliary independent marker of DFS and OS. These findings strongly indicate that the subcellular localization of VDR is crucial in determining BC prognosis. The expression of nuclear VDR appears to have a protective effect, while cytoplasmic VDR is associated with a more aggressive disease course. The data may help identify subgroups of patients with high-risk BC, possibly leading to specific options for targeted tumor therapy
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    Intratumor heterogeneity in human parathyroid tumors
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Verdelli, C.; Tavanti, G.S.; Corbetta, S.
    Parathyroid tumors are the second most common endocrine neoplasia after thyroid neoplasia. They are mostly associated with impaired parathormone (PTH) synthesis and release determining the metabolic and clinical condition of primary hyperparathyroidism (PHPT). PHPT is the third most prevalent endocrine disorder, mainly affecting postmenopausal women. Parathyroid benign tumors, both adenomas of a single gland or hyperplasia involving all the glands, are the main histotypes, occurring in more than 95% of PHPT cases. The differential diagnosis between benign and malignant parathyroid lesions is a challenge for clinicians. It relies on histologic features, which display significant overlap between the histotypes with different clinical outcomes. Parathyroid adenomas and hyperplasia have been considered so far as a unique monoclonal/polyclonal entity, while accumulating evidence suggest great heterogeneity. Intratumor parathyroid heterogeneity involves tumor cell type, as well as tumor cell function, in terms of PTH synthesis and secretion, and of expression patterns of membrane and nuclear receptors (calcium sensing receptor, vitamin D receptor, α-klotho receptor and others). Intratumor heterogeneity can also interfere with cell molecular biology, in regard to clonality, oncosuppressor gene expression (such as MEN1 and HRPT2/CDC73), transcription factors (GCM2, TBX1) and microRNA expression. Such heterogeneity is likely involved in the phenotypic variability of the parathyroid tumors, and it should be considered in the clinical management, though at present target therapies are not available, with the exception of the calcium sensing receptor agonists.