Perirenal Adipose Tissue-Current Knowledge and Future Opportunities.

The perirenal adipose tissue (PRAT), a component of visceral adipose tissue, has been recently recognized as an important factor that contributes to the maintenance of the cardiovascular system and kidney homeostasis. PRAT is a complex microenvironment consisting of a mixture of white adipocytes and dormant and active brown adipocytes, associated with predipocytes, sympathetic nerve endings, vascular structures, and different types of inflammatory cells. In this review, we summarize the current knowledge about PRAT and discuss its role as a major contributing factor in the pathogenesis of hypertension, obesity, chronic renal diseases, and involvement in tumor progression. The new perspectives of PRAT as an endocrine organ and recent knowledge regarding the possible activation of dormant brown adipocytes are nowadays considered as new areas of research in obesity, in close correlation with renal and cardiovascular pathology. Supplementary PRAT complex intervention in tumor progression may reveal new pathways involved in carcinogenesis and, implicitly, may identify additional targets for tailored cancer therapy.

Tryptase-positive and CD117 Positive Mast Cells Correlate with Survival in Patients with Liver Metastasis.

The prognostic value of mast cells (MCs) in patients with liver metastases is a relatively new topic. The present study comparatively assessed tryptase-positive (MCT(+)) and CD117(+) MCs in liver metastases from various sites and correlated their expression with clinicopathological prognostic factors and survival. Our data pointed to differences in MCT and CD117 expression in liver metastases that seem to be related to the origin of the primary tumor. For colon cancer metastases, intra-tumor MCT(+) MCs were significantly correlated with tumor grade and nodal status, while peritumoral MCT(+) MCs and peritumoral CD117(+) MCs were significantly correlated with overall survival. No significant correlations between MCT(+) and CD117(+) MC number and clinicopathological parameters or survival were found for gastric cancer metastases. To the best of our knowledge, this is the first report regarding MC involvement in liver metastases from different malignant tumors correlated with clinicopathological parameters and overall survival. Different mast cell phenotype together with their specific correlation with tumor grade, nodal status and survival suggest their involvement in the metastatic process in a specific manner related to tumor origin. Mast cells from liver metastases remain a questionable issue regarding their origin, pathogenic role and their ability to be potential targets for adjuvant therapy.

RELATIONSHIP BETWEEN THE PROANGIOGENIC ROLE OF EG-VEGF, CLINICOPATHOLOGICAL CHARACTERISTICS AND SURVIVAL IN TUMORAL OVARY.

AIM: To prove the presence of EG-VEGF in tumor ovary and to analyze its involvement in the ovarian carcinogenesis, as promoter of angiogenesis, in relationship with the clinicopathological prognostic factors and survival. METHODS: The study group comprises tumor tissue specimens from 50 cases of surgically treated ovarian cancer that were immunohistochemically investigated. A scoring system based on the percentage of positive cells and the intensity of staining was applied for the semiquantitative assessment of EG-VEGF, as negative or positive. Statistics involved χ2 test, and Kaplan-Meier and log-rank test. RESULTS: EG-VEGF was positive in 35 cases (70%) and negative in 15 cases (30%). Our data confirmed the predominance of EG-VEGF positivity in the serous subiype as compared to endometrioid and clear cell subtypes, and its absence in mucinous subtype. Moreover, we demonstrated that EG-VEGF is overexpressed mainly in high-grade ovarian carcinomas (type II) than in low-grade ones. Significant differences were registered between the EG-VEGF positive or negative expression and tumor stage and histological subtypes, respectively. Survival analysis showed no differences in patient's survival and EG-VEGF positive and negative cases. CONCLUSIONS: The analysis of EG-VEGF expression in ovarian tumors points out the relationship between the enhanced potential for tumor angiogenesis and the tumor aggressivity.

High variability in MMP2/TIMP2 and MMP9/TIMP1 expression in secondary liver tumors.

The assessment of MMPs/TIMPs expression in various primary tumors has potential prognostic values. Considering the paucity of studies in secondary liver tumors, our aim was to study the expression of MMP2, MMP9, TIMP1, and TIMP2 in secondary hepatic cancer, focusing on their variability in the malignant cells. The study group included 25 cases of liver metastases of colorectal cancer, diagnosed and surgically treated at "Sf. Spiridon" University Hospital of Iassy, Romania. Immunohistochemistry for MMP2, MMP9, TIMP1, and TIMP2 has been performed, followed by the semi-quantitative assessment of the markers using a scoring system based on the positive tumoral cells percentage and the staining intensity. The expression of investigated markers revealed an increased staining variability. The scores showed that MMP2/TIMP2 and MMP9/TIMP1 immunoreactivity was extremely heterogeneous within the analyzed group, with a dominant weak expression for MMP2 and MMP9, in contrast to strong TIMP2 and TIMP1 expression. Ten different patterns of expression of the investigated markers have been identified. No major differences between the expression of MMP2 (14 positive cases) and MMP9 (16 positive cases) could be detected. Our results sustain the inverse correlation between MMP and the correspondent TIMP expression, supporting the hypothesis that MMPs/TIMPs balance has mainly an inhibitory effect on invasiveness. Our study demonstrated that tumoral cells are adapted to MMPs:TIMPs production in the liver microenvironment. The lack of significant differences between MMP2 and MMP9 expression shows that the activity of both MMPs is independent, without reciprocal influences.

E-cadherin expression in molecular types of breast carcinoma.

E-cadherins are epithelial morphological stabilizers, performing complex functions as receptors, providers of cellular and tissular structural integrity, and functional interactive mediators. Structural and functional unbalance initiated due to E-cadherin expression loss results in direct effects on carcinogenesis specific biological processes, as cellular invasion and proliferation. We investigated the E-cadherin expression aiming (i) to identify the differences in the molecular subtypes of breast cancer, (ii) to analyze the correlations between E-cadherin and specific clinicopathological and molecular characteristics. The study included 42 cases that were investigated immunohistochemically using a panel of antibodies (ER, PR, Her2/neu, CK5/6, EGFR), which permitted a diagnostic in compliance with the molecular classification, followed by the E-cadherin evaluation. The semi-quantitative assessment of E-cadherin was performed using a scoring system based on the positive cells percentage and the staining intensity. Our results showed, according to the molecular subtypes, a strong positive E-cadherin expression in 26 cases (luminal A subtype - nine cases, luminal B subtype - five cases, HER2 subtype - three cases, basal-like subtype - seven cases, unclassified subtype - two cases), and a weak positive one in 16 cases (luminal A subtype - six cases, luminal B subtype - eight cases, HER2 subtype - one case, basal-like subtype - one case). The statistical analysis revealed significantly statistical differences between E-cadherin and tumoral grade (p=0.0208), histological subtype (p=0.0081), triple negative molecular subtypes and non-triple negative, respectively (p=0.0361). These findings support the potential value of E-cadherin for a supplementary differentiation of molecular subtypes, based on the biological significance of its capacity of expression.

Relationship between Kuppfer cells, inflammation, and fibrosis in chronic hepatitis B and C.

Kupffer cells are liver parenchymal components of the immune system able of intervention in pathogenic mechanisms involved in viral hepatitis and tumoral lesions. Our study aimed to evaluate the Kupfferian hyperplasia in chronic hepatitis B and C, and to correlate with the severity of liver lesions, focusing on the modality in which Kupffer cells modulate the necroinflammatory events and fibrosis specific for chronic hepatitis morphologic substrate. We investigated 33 cases with chronic hepatitis B and 38 cases with chronic hepatitis C, diagnosed according to Ishak score (in chronic hepatitis B and C) and METAVIR score (in chronic hepatitis C). Kuppfer cells were immunohistochemical labeled, by using an anti-CD68 antibody and heat-induced epitope retrieval (HIER) technique. The sinusoidal reaction expressed by CD68 (+) cells hyperplasia progressively increases along with the intensity of necroinflammatory activity and with the amplitude of fibrosis lesions. Statistically significant differences between Kupffer cells number and the degree of necroinflammatory activitiy and fibrosis, respectively (Ishak score) have been identified in both types of chronic hepatitis. However, no significant differences have been registered when comparing the Kupffer cells number corresponding to each degree of necroinflammatory activity and of fibrosis, in chronic hepatitis B versus C, respectively. Our results demonstrate the relationship between Kupffer cells and the severity degree of the disease, without differences between chronic hepatitis B and C. Consequently, we may appreciate that the chronic hepatitis C specific lesions progression, different from that of chronic hepatitis B, is influenced by a different behavior of Kupffer cells, and not by their effective