P53 and TLR4 expression are prognostic markers informing progression free survival of advanced stage high grade serous ovarian cancer.

OBJECTIVE: New prognostic biomarkers, and bio-signatures, are urgently needed to facilitate a precision medicine-based approach to more effectively treat patients with high-grade serous ovarian cancer (HGSC). In this study, we analysed the expression patterns of a series of candidate protein biomarkers. METHODS: The panel of markers which included MyD88, TLR4, MAD2, PR, OR, WT1, p53, p16, CD10 and Ki67 was assessed using immunohistochemistry in a tissue microarray (TMA) cohort of n = 80 patients, composed of stage 3-4 HGSCs. Each marker was analysed for their potential to predict both overall survival (OS) and progression-free survival (PFS). RESULTS: TLR4 and p53 were found to be individually predictive of poorer PFS (Log Rank, p = 0.017, p = 0.030 respectively). Cox regression analysis also identified high p53 and TLR4 expression as prognostic factors for reduced PFS (p53; HR=1.785, CI=1.036-3.074, p = 0.037 and TLR4; HR=2.175, CI=1.112-4.253, p = 0.023). Multivariate forward conditional Cox regression analysis, examining all markers, identified a combined signature composed of p53 and TLR4 as prognostic for reduced PFS (p = 0.023). CONCLUSION: Combined p53 and TLR4 marker assessment may help to aid treatment stratification for patients diagnosed with advanced-stage HGSC.

Imaging features of atypical adrenocortical adenomas: a radiological-pathological correlation.

OBJECTIVE: Adrenal adenomas are frequently picked up incidentally on cross-sectional imaging and are known to have a classic imaging appearance on CT and MRI. However, not all adrenal adenomas have this typical radiologic appearance. Our aim is to present the radiological features of atypical adrenocortical adenomas with pathological correlation. METHODS: All the imaging from the pathologically proven adrenal adenoma cases in our hospital (Tallaght University Hospital, Dublin, Ireland) database (from 2004 to 2019) was reviewed. 8 out of 48 cases (16%) had an atypical radiological appearance and were selected for presentation. RESULTS: Eight cases demonstrated atypical radiological features including heterogeneous density, incomplete washout on post-contrast imaging, the presence of macroscopic fat and calcification. Lipomatous metaplasia was present in two of the cases pathologically. CONCLUSION: Adrenocortical adenomas are the most common adrenal mass encountered on CT, however, may not always have classic imaging features. Radiologists should be familiar with both the typical and atypical imaging manifestations of these benign adrenal lesions. ADVANCES IN KNOWLEDGE: This paper comprehensively describes the atypical features of adrenocortical adenomas with case examples and radiologic-pathologic correlation. Guidelines and an approach to the work-up of adrenal lesions with atypical appearances are also provided.

Trait dominance and cardiovascular functioning during social stress.

Cardiovascular reactivity (CVR) to stress has been found to be an important indicator of future ill health, and individual differences in personality have been posited to explain disparities in outcomes. Dominance is associated with forceful persons who desire hierarchy in social interactions. This study investigated dominance and CVR during social or asocial stressors. Sixty-one women, categorized as low, moderate, or high in dominance using the Jackson Personality Research Form, completed a social or asocial stressor while undergoing cardiovascular measurement during baseline, stressor, and recovery phases. A 3 × 2 × 3 analysis of covariance revealed a significant Phase × Stressor × Dominance interaction for systolic blood pressure (SBP). Women with lower and moderate dominance-but not women with higher dominance-exhibited greater SBP responses to stress in the social condition compared with the asocial condition. No significant difference was found for women with higher dominance, indicative of blunted SBP during the social stressor. During recovery, women with lower dominance had marginally elevated SBP in the social condition compared with the asocial condition. The current study extends prior knowledge of the association between dominance and CVR, such that greater dominance was associated with blunted SBP and lower dominance was associated with attenuated recovery to social stress.

Trait dominance is associated with vascular cardiovascular responses, and attenuated habituation, to social stress.

Both exaggerated and diminished levels of cardiovascular reactivity have been associated with cardiovascular ill health. Dysregulation of hemodynamic mechanisms which control cardiovascular functioning may account for some individual differences in health outcomes. Trait dominance has also been associated with poor cardiovascular health in studies of humans and animals. The current study investigated the relationship between trait dominance and cardiovascular habituation to repeated social stress in humans. Forty-seven undergraduate women completed two consecutive speech tasks, preceded by a baseline period, and separated by an inter-task resting phase. Continuous cardiovascular functioning was monitored using the Finometer device. The trait dominance subscale of the Jackson Personality Research Form was completed. Mixed ANCOVA with trait dominance revealed a significant 3 (dominance) × 4 (phase) interaction for total peripheral resistance (TPR), such that TPR varied across experimental phases and was associated with trait dominance, F(1, 43)=12.88, p=.001, partial η(2)=.23. Further mixed ANCOVA for TPR reactivity to Exposures 1 and 2 revealed a significant 3 × 2 interaction with trait dominance, F(2, 40)=7.77, p=.001, partial η(2)=.28, such that higher dominance was associated with attenuated TPR habituation to Exposure 2. Trait dominance was significantly associated with vascular-oriented cardiovascular functioning, and with attenuated habituation to social stress. Vascular-dominated stress responses have in some instances been associated with ill-health, suggesting that a failure to habituate to stress, and a vascular response style could reflect potential mechanisms through which dominance is associated with poor future cardiovascular health.