Immunohistochemical Expression of Programmed Death Ligand 1(PDL1) in Endometrial Carcinoma and Its Relation to CD4 and CD8 Positive Immune Cells.

OBJECTIVES: Endometrial cancer (EC) is the most common cancer of the female genital tract. Egypt showed a significant increase in incidence lately of which 25% were premenopausal. Advanced or recurrent disease are mostly unresectable and the traditional adjuvant therapy give modest results with devastating side effects. Late discoveries of immune checkpoint inhibitors have produced promising results. Programmed cell death 1 (PD1) is an immune inhibiting receptor on surface of lymphocytes, which plays critical roles in maintaining immunological self-tolerance. There are two ligands for this receptor, PDL1 and PDL2. PD-L1 is expressed on tumor cells; attaches to PD1, allowing tumor cells to escape from the host immune response. Its prognostic significance in various tumors is controversial and its significance in ECs has just begun to be investigated. Therefore, we investigated the relationship between PDL1 expression and different clinicopathologic parameters in EC cases and its correlation with CD4 and CD8 immune cells, in order to identify the predictive biomarkers for the outcome by immune therapy. METHODS: Hundred, paraffin tissue blocks of EC cases were collected and stained with antibodies against PDL1,CD4 and CD8. RESULTS: PDL1 was positive in 67% of cases in tumor cells and in 61% of cases in immune cells. CD4 and CD8 were expressed in 79% of cases. Statistically significant correlations were observed between PDL1 expression and patients mean age, LVSI, TILS score and CD4+/CD8+ expression. CONCLUSION: Those variables can stratify candidates who can benefit most from immunotherapy, or can be chosen for further high cost molecular investigations application.

Polo-Like Kinase 1(PLK1) Immunohistochemical Expression in Triple Negative Breast Carcinoma: A Probable Therapeutic Target.

BACKGROUND: Breast cancer is the most commonly diagnosed female cancer and is a major cause of cancer-related deaths in women. Triple-negative breast cancer (TNBC) is defined as ER, PR and HER2 negative, which are characterized by rapid progression with low survival rates with limited therapeutic choices. Polo-like kinase 1 protein acts as a cell division regulator which is highly expressed in many tumors making it a potentially valuable target for antiproliferative therapies. In this study we tried to evaluate the value of this marker as a possible therapeutic target in TNBC. METHODS: This research studied the immunohistochemical expression of PLK1 done on 49 paraffin blocks of TNBC female patients and then correlated with the different clinicopathological parameters. RESULTS: Our results showed high PLK1 expression in 91.9% of cases. Most of the high grade tumors showed high PLK1 high score (76.9%). All cases showing lymph node metastasis showed high PLK1 expression, implying a statistically significant correlation between PLK1 expression and tumor grade as well as N stage. CONCLUSION: PLK1, although a negative prognostic factor, but is a promising therapeutic target for treating TNBC patients.

In-vivo assessment of the osteo-protective effects of eugenol in alveolar bone tissues.

Estrogen deficiency following menopausal provokes alveolar bone loss, remodeling and inflammation. Eugenol is a phenolic compound with wide dental applications and anti-inflammatory properties. In the present study, the potential protective role of eugenol against alveolar bone deformities was investigated in an ovariectomized (OVX) rodent model. Two doses of eugenol (2.5 and 5 mg/kg/d) were administered to OVX animals for 12 weeks. In Serum, markers of bone metabolism and pro-inflammatory cytokines were estimated using ELISA. Alveolar bone morphometry was analyzed using high-resolution micro-computed tomography (CT). Bone histological analysis (H&E stain) was also performed. Alveolar bone expression of osteoclastogenesis modulating factors, such as osteoprotegerin (OPG), receptor activator of nuclear factor kappa-b ligand (RANKL) and inflammatory mediators, were measured using immunohistochemistry. Eugenol failed to correct elevated body weights and uterine atrophy in OVX rats. The significant elevation of bone metabolic markers and inflammatory cytokines in OVX animals were markedly improved by eugenol treatment, particularly the higher dose. Eugenol treatment considerably attenuated morphometric trabecular alterations of the alveolar bone and improved alveolar resorption and gingival infiltration. Alveolar bone of OVX animals showed augmented expression of RANKL, OPG and inflammatory cytokines, which were corrected by eugenol treatment. Alveolar bone loss and remodeling associated with estrogen insufficiency was ameliorated by eugenol owing to its anti-inflammatory properties, suggesting an extra dental impact for eugenol.