Angelos Tsipis

The prognostic significance of COX-2 and survivin expression in ovarian cancer

We investigated the prognostic significance of cyclooxygenase-2 (COX-2) and survivin in ovarian carcinoma. Imprint smears were obtained from 100 ovarian carcinoma specimens and were studied immunocytochemically for the expression of COX-2 and survivin. The results were correlated with several clinicopathological parameters, including 5-year survival. Increased COX-2 staining pattern correlated with a non-mucinous histological type (p=0.008), increased stage (p<0.0001), high histological grade (p<0.0001), and reduced survival rates (p<0.00001). Survivin expression was strongly associated with increased stage (p<0.0001), increased histological grade (p<0.0001), and reduced survival (p<0.00001). Elevated survivin expression also correlated significantly with pre-menopausal status (p=0.033). In addition, COX-2 and survivin staining patterns correlated strongly with one another (p<0.0001). However, on multivariate analysis, an independent prognostic value was found only for tumor stage and grade. The findings of our study indicate that the increased expression of COX-2 and survivin in ovarian cancer is associated with one another and with several adverse clinicopathologic parameters, including reduced survival, thus suggesting a role of these molecules in disease progression. Further investigations of the exact prognostic and therapeutic implications of COX-2 and survivin expression are strongly warranted.

CD24 expression has a prognostic impact in breast carcinoma.

We investigated the prognostic significance of BAG-1 and CD24 in invasive breast carcinomas. Seventy cases of invasive breast carcinoma were studied immunocytochemically for the expression of BAG-1 and CD24. The results were correlated with several prognostic parameters, including 5-year survival. Univariate analysis showed a significant correlation of BAG-1 and CD24 overall positive staining with several adverse prognostic parameters, such as increased stage (p<0.0001), tumor grade 3 (p=0.016 and p=0.02, respectively), positive lymph nodes (p<0.0001), and increased tumor size (p<0.0001). Similar results were found for BAG-1 nuclear staining, as well as for positive cytoplasmic CD24 expression. Both of our markers studied had a significant, negative effect on survival. Multivariate analysis further revealed an independent prognostic impact for CD24 overall staining. The results of our study showed that overall cytoplasmic and especially nuclear BAG-1 expression, as well as overall and cytoplasmic CD24 expression, correlates with adverse prognostic parameters. An independent prognostic value for overall CD24 staining was also demonstrated.

The significance of Survivin and Nectin-4 expression in the prognosis of breast carcinoma.

To investigate the prognostic significance of Survivin and Nectin-4 expression in breast carcinomas. Imprint smears were obtained from 140 breast carcinoma specimens and studied immunocytochemically for the expression of Survivin and Nectin-4. The results were correlated with several clinicopathological parameters, including five-year survival. Increased Survivin staining pattern correlated with increased grade (p < 0.0001), increased lymph node invasion (p < 0.0001), increased tumor size and reduced survival (p < 0.0001). Elevated Nectin-4 expression also correlated significantly with increased grade (p < 0.0001), increased tumor size (p < 0.0001) and reduced survival (p < 0.0001). In addition, Survivin and Nectin-4 staining patterns correlated strongly with one another (p < 0.0001). However, on multivariate analysis, neither Survivin nor Nectin-4 expression seemed to have an independent impact on survival in our study cases. The findings of our study suggest that increased expression of Survivin and Nectin-4 may indicate a worse prognosis in breast cancer patients. The exact implications of the expression of these markers in breast cancer prognosis and treatment remain to be clarified.

Significance of cyclooxygenase 2, EZH-2 polycomb group and p53 expression in actinic keratosis and squamous cell carcinomas of the skin.

Abstract:The development and progression of squamous cell carcinoma (SCC) of the skin is characterized by an accumulation of molecular changes. The aim of this study was to investigate the association of the immunohistochemical expression of cyclooxygenase-2 (COX-2), enhancer of zeste homolog 2 (EZH-2), and p53 in actinic keratosis (AK) and SCC and detect any differences between invasive and preinvasive squamous epidermal lesions. Forty-three cases with AK, 38 with SCC, and 9 with SCC arising on AK (SCC/AK) were studied. For COX-2 immunostaining, weak or no reaction was associated with AK (58.10% of cases), whereas moderate or strong reaction with SCCs (34.2% and 39.5%, respectively). Furthermore, 88.9% of the “mixed” SCC/AK specimens demonstrated moderate reaction (&khgr;2 = 29.924, P < 0.0001). For EZH-2 immunostaining, a weak or no reaction was observed in 62.8% of AK cases, whereas a moderate reaction was observed in 42.1% of SCCs and 77.8% of “mixed” SCC/AK cases (&khgr;2 = 18.91, P = 0.001). Weak immunoreactivity of p53 was associated with AK (58.1%), moderate with SCC (44.7%), and strong with SCC/AK lesions (66.7%) (&khgr;2 = 15.999, P = 0.003). COX-2, p53, but mainly EZH-2 immune expression seems to be strongly associated with the biological potential of squamous epidermal cells and seems to be differentiating SCC by comparison to AK of the skin. The value of the combined expression of these markers is worth being further investigated as an additional tool for diagnostic, prognostic, and possibly, therapeutic use.

Novel Oral Anticoagulants in Peripheral Arterial and Coronary Artery Disease

Atherosclerosis comprises of a chronic disease of the vessels which mainly targets the arterial system. The diseases main characteristic is the accumulation of inflammatory cells, lipids, smooth muscle cells and connective tissue within the vascular intima layer. The atherosclerotic lesion can be more accurately defined as a fibro-inflammatory lipid plaque. The pathogenesis of the atherosclerotic plaque is a progressive and additive process that usually occurs over decades. Antiplatelet and anticoagulant agents have been the major elements of large trials since decades, in an attempt to promote the primary and secondary prevention of atherothrombosis. The atherosclerotic plaque rupture and the following thrombosis involve, among others, activation of both platelets and coagulation factors, therefore a potential combination of antiplatelet and anticoagulant therapy, particularly in the setting of secondary prevention has been reconsidered in the light of the newly developed oral anticoagulants.

Tumor Protein p53 (TP53) Gene and Left Main Coronary Artery Disease

Patients with left main (LM) coronary artery disease (CAD) are at the highest risk of cardiovascular events. We evaluated possible gene polymorphisms of tumor protein 53 (TP53, rs1042522, p.Arg72Pro) that can differentiate LM-CAD from patients with more peripheral CAD (MP-CAD) and healthy participants (control group) in 520 individuals (LM-CAD, n = 175; MP-CAD, n = 185; and control group, n = 160). Patients with LM-CAD had the lowest Arg/Arg genotype frequency (36.0%) compared with the MP-CAD (57.3%) and control groups (61.9%), P < .001 for both comparisons. Similarly, the Arg allele was more frequent in the control group than in patients with MP-CAD (78.8% vs 73.2%; P = .007) and LM-CAD (78.8% vs 64.0%; P < .001). The Arg/Pro genotype was more frequent in the LM-CAD group compared with the MP-CAD and control groups (56.0, 31.9, and 33.8, respectively, P < .001 for both comparisons). Furthermore, the frequency of Arg/Arg genotypes was the lowest in the LM-CAD group compared with the MP-CAD and control groups. Knowing that TP53 is an antioncogene protein that acts as a tumor suppressor and regulator of apoptosis, the lowest frequency of Arg/Arg genotype observed in these high-risk patients may indicate lower protection from the atherosclerosis process. Replication studies are needed to evaluate this association.