Abstract
The chronic inflammation influences a microenvironment, where as a result of losing control over tissue homeostatic mechanisms, the carcinogenesis process may be induced. Inflammatory response cells can secrete a number of factors that support both initiation and progression of cancer and also they may consequently induct an epithelial-mesenchymal transition (EMT), the process responsible for development of distant metastasis. Macrophage migration inhibitory factor (MIF) acts as a pro-inflammatory cytokine that is considered as a link between chronic inflammation and tumor development. MIF can function as a modulator of important cancer-related genes expression, as well as an activator of signaling pathways that promotes the development of prostate cancer. The study was performed on FFPE tissues resected from patients who underwent radical prostatectomy. To investigate the relationship of studied proteins with involvement in tumor progression and initiation of epithelial-to-mesenchymal transition (EMT) process, we selected clinicopathological parameters related to tumor progression. Immunohistochemical analyses of MIF, SOX-4, β-catenin and E-cadherin were performed on TMA slides. We found a statistically significant correlation of overall β-catenin expression with the both lymph node metastasis (p<0.001) and presence of angioinvasion (p = 0.012). Membrane β-catenin expression was associated with distant metastasis (p = 0.021). In turn, nuclear MIF was correlated with lymph node metastasis (p = 0.003). The positive protein-protein correlations have been shown between the total β-catenin protein expression level with level of nuclear SOX-4 protein expression (r = 0.27; p<0.05) as well as negative correlation of β-catenin expression with level of nuclear MIF protein expression (r = -0.23; p<0.05). Our results seem promising and strongly highlight the potential role of MIF in development of nodal metastases as well as may confirm an involvement of β-catenin in disease spread in case of prostate cancer.
Highlights
Prostate cancer (PCa) is the most common malignancy as well as the fifth cause of cancerrelated death among men worldwide [1]
Membrane and cytoplasmic E-cadherin expression was confirmed in 98.8% (84) of specimens, in turn nuclear level of E-cadherin appeared in 97.6% (83) of cases
The glandular cells of adjacent healthy prostate areas showed lack or weak Sry-related HMG-BOX gene 4 (SOX-4) nuclear immunostaining and they were accepted as a negative internal control
Summary
Prostate cancer (PCa) is the most common malignancy as well as the fifth cause of cancerrelated death among men worldwide [1]. PCa still remains a highly treatable neoplasm if it is diagnosed as localized disease at its an early stage and constantly monitored [3]. These patients could be usually treated by radical prostatectomy or radiotherapy, which guarantee a successful treatment outcome in most cases. By the significant proportion of patients the PCa undergo progression to a highly advanced, metastatic stage of disease for which treatment options are limited and the prognosis is uncertain [5]. Based on the Surveillance, Epidemiology, and End Results Program (SEER) database, the 5-year relative survival rate for PCa cases with localized and regional stage is at 100%, whereas at the metastatic stage the level is only 29% [6]
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