Abstract
A number of reports indicated that Aurora-A or Aurora-B overexpression represented a negative prognostic factor in several human malignancies. In thyroid cancer tissues a deregulated expression of Aurora kinases has been also demonstrated, butno information regarding its possible prognostic role in differentiated thyroid cancer is available. Here, weevaluated Aurora-A and Aurora-B mRNA expression and its prognostic relevance in a series of 87 papillary thyroid cancers (PTC), with a median follow-up of 63 months. The analysis of Aurora-A and Aurora-B mRNA levels in PTC tissues, compared to normal matched tissues, revealed that their expression was either up- or down-regulatedin the majority of cancer tissues. In particular, Aurora-A and Aurora-B mRNA levels were altered, respectively, in 55 (63.2%) and 79 (90.8%) out of the 87 PTC analyzed.A significant positive correlation between Aurora-A and Aurora-B mRNAswas observed (p=0.001). The expression of both Aurora genes was not affected by the BRAFV600E mutation. Univariate, multivariate and Kaplan-Mayer analyses documented the lack of association between Aurora-A or Aurora-B expression and clinicopathological parameterssuch as gender, age, tumor size, histology, TNM stage, lymph node metastasis and BRAF status as well asdisease recurrences or disease-free interval. Only Aurora-B mRNA was significantly higher in T(3-4) tissues, with respect to T(1-2) PTC tissues. The data reported here demonstrate that the expression of Aurora kinases is deregulated in the majority of PTC tissues, likely contributing to PTC progression. However, differently from other human solid cancers, detection of Aurora-A or Aurora-B mRNAs is not a prognostic biomarker inPTC patients.
Highlights
The incidence of differentiated thyroid cancers (DTC) has been increasing over the last decades, mainly due to the increasing ability to diagnose malignant transformation in small nonpalpable nodules [1,2,3,4]
The stratification and prognosis of DTC patients rely on clinicopathological variables such as the patient’s age, tumor size, histology, lymph nodal or distant metastasis [8,9,10,11]
To assess the effect of BRAFV600E mutation on the expression of Aurora-A and Aurora-B we first analyzed the mRNA level of both genes in BRAFV600E papillary thyroid carcinoma (PTC) tumors (n = 37), compared with those harboring the wild type protein (n = 38) (Fig. 2A)
Summary
The incidence of differentiated thyroid cancers (DTC) has been increasing over the last decades, mainly due to the increasing ability to diagnose malignant transformation in small nonpalpable nodules [1,2,3,4]. The stratification and prognosis of DTC patients rely on clinicopathological variables such as the patient’s age, tumor size, histology, lymph nodal or distant metastasis [8,9,10,11]. These parameters, are capable of providing only a rough prediction of the disease outcome, placing patients with very different disease-specific progression and survival times within the same risk group. They fail to predict the risk of cancer recurrence. The identification of new prognostic molecular biomarkers able to testify tumor aggressiveness is required [11,12,13,14,15,16,17]
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