Overexpression of enhancer of zeste homolog 2 (EZH2) and focal adhesion kinase (FAK) in high grade endometrial carcinoma

ObjectiveThe deregulation of E-cadherin is associated with Src/FAK signaling axis and histone deacetylase (HDAC)/EZH2 activity. However, the association between EZH2 and FAK and its clinical significance in endometrial carcinoma has not been reported.Methods202 archived cases of endometrial carcinoma (1996–2000) were reviewed and divided into two subtypes. TMAs were developed as per established procedures. EZH2, FAK, and pFAK immunohistochemical stains were performed and the expression was scored as negative (0), low (1) and high (2). Proper statistical analysis was used to assess the correlation between the expression profiles and the clinicopathological parameters and clinical outcome.ResultsA total of 141 (69.8%) type-1 tumors and 61 (30.2%) type-2 tumors were identified. EZH2 overexpression was identified in 7.6% of type-1 tumors vs. 63% of type-2 tumors (p < 0.001). FAK and pFAK overexpression was only seen in 24.8% and 1.7% of Type-1 tumors as compared to 72% and 58.8% of type-2 tumors, respectively (p < 0.001). A positive correlation between the expression of EZH2, FAK, pFAK and PTEN (p < 0.0001) was found. The overexpression of EZH2, FAK, and pFAK were significantly associated with high histologic grade, angiolymphatic invasion, lymph node metastasis, myometrial invasion and cervical involvement (p < 0.01). Kaplan–Meier analysis demonstrates that the overexpression of EZH2 (p = 0.0024), FAK and pFAK (p = 0.0001) was significantly associated with decreased overall survival.ConclusionThe overexpression of EZH2, FAK and pFAK correlates with well established pathologic risk factors and may predict a more aggressive biologic behavior in endometrial carcinoma, transforming these proteins into potential therapeutic targets for treatment of endometrial cancer.     

Relationship between serum copper and protein thiols in hyperlipidemic patients

Objective:To measure serum copper and protein thiols along with lipid profile in hyperlipidemic patients and to establish the relationship between serum copper,protein thiols and lipid profile parameters.Methods: The study group consisted of 26 newly diagnosed hyperlipidemic patients not associated with any other systemic diseases and 26 age and sex matched healthy controls.Fasting lipid profile was done by enzymatic method using automated analyzer.Serum copper and protein thiols were measured spectrophotometrically.Results: Serum copper and protein-SH levels were significantly decreased in cases(P<0.01,P<0.01) compared to controls.Serum copper correlated positively with protein thiols(r=0.800,P<0.01) and negatively with LDL cholesterol(r=-0.351 P<0.05).Conclusion: Serum copper and protein thiols were decreased in hyperlipidemia and they correlated positively indicating protective role of copper in preventing homocysteinylation of protein and hence in preventing atherosclerosis.     

Surgery for breast cancer in the elderly--how relevant?

Studies suggest that elderly women receive less aggressive treatment, experience higher disease progression and mortality from breast cancer. We report on an experience of 256 consecutive cases of symptomatic breast cancer in a population of over 75 years of age. 142/256 patients underwent surgical intervention in the form of breast conserving surgery or mastectomy, 114/256 did not. Mean follow up was 6.4 years. Our results show a statistically significant association between surgery and survival (p = 0.05, CI 0.00046-0.19641) and a strong statistically significant association between surgery and disease progression/recurrence (p = 0.001, CI 0.08713-0.03145). Women treated conservatively are significantly less fit hence suffering high cancer unrelated mortality; as a consequence they suffer higher disease related progression and mortality. In our study surgical treatment with adjuvant endocrine and/or radiotherapy was associated with a statistically significant advantage in terms of disease related mortality and local disease control.     

Molecular typing of epithelial ovarian carcinomas using inflammatory markers

BACKGROUND:

Ovarian epithelial carcinomas have recently been classified as slow growing type I tumors and rapidly growing highly aggressive type II tumors. The present study sought to molecularly characterize type I and II tumors using known molecular markers.

METHODS:

Specimens from 213 patients with ovarian carcinoma were categorized as type I or type II, and evaluated by immunohistochemistry for the inflammatory markers glucose transporter protein‐1 (Glut‐1), inducible nitric oxide synthase (iNOS), cyclooxygenase‐1 (COX‐1), cyclooxygenase‐2 (COX‐2), and nuclear factor kappa B. Statistical analysis was performed to investigate whether these molecular markers could distinguish between type I and type II tumors. Kaplan‐Meier survival curves and COX regression analysis were used to determine the prognostic effect of these markers on survival in the 2 types of tumors.

RESULTS:

Overexpression of COX‐1, COX‐2, iNOS, and Glut‐1 was significantly higher in type II tumors (P < .05). Women with type II tumors had a poorer median survival (60 months) as compared with those with type I tumors (141 months) (P = .0001). Multivariate analysis revealed type II tumors, late stage, and age >60 years as significant predictors of poor survival. For type II tumors, median survival of patients with tumors overexpressing COX‐2 was 44 compared with 85 months for those with tumors with low COX‐2 expression (P = .029). Looking at both type I and II tumors, the number of markers simultaneously overexpressed in each tumor was a significant predictor of poor patient survival (P = .005).

CONCLUSIONS:

The present study demonstrates that the new proposed histologic classification of ovarian epithelial carcinomas correlates with a distinct expression of inflammatory pathway proteins. High expression of these markers may explain the different biologic behavior of these 2 tumor types and provide targets for therapy. Cancer 2011. © 2010 American Cancer Society.     

Comparison of the QTDT Analysis for IgE in the CSGA Data Set

Over the past few years at least 13 transmission/disequilibrium test (TDT)‐based tests have been developed for quantitative (Q) traits for the assessment of association or linkage in the presence of the other. A total of six of these QTDT methods were used to analyze log₁₀IgE in the Collaborative Study on the Genetics of Asthma data set. Only moderate agreement was found between the tests. The results of the QTDT analyses were only slightly affected by the use of gender and age as covariates. Results from analysis of IgE and log₁₀IgE were inconsistent. Our conclusion is that there is only modest agreement among the QTDT methods examined, covariates should be used even if they have a small effect, and that data should be normalized before analysis. © 2001 Wiley‐Liss, Inc.     

Diagnostic efficacy of ischemia modified albumin and its correlation with lipid profile,oxidative stress in acute myocardial infarct patients on admission

ObjectiveTo evaluate the diagnostic efficacy of ischemia modified albumin (IMA) and its correlation with lipid profile, oxidative stress in acute myocardial infarct (AMI) patients attending Cardiology Emergency Department (ED).MethodsAt presentation serum IMA in conjunction with electrocardiogram (ECG) and cardiac troponin T (CTnT) was evaluated in 35 AMI patients attending the ED within 6 hours of chest pain. These patients were subjected to standardized diagnostic procedures and treatment. Thirty five healthy volunteers were enrolled as control.ResultsIMA showed a higher level in ischemic patients than in control with the highest sensitivity (77%) in comparison to CTnT and ECG. With CTnT or ECG, IMA documented a sensitivity of 83% and 88%, respectively. Whereas with both CTnT and ECG, IMA identified 94% of AMI patients with the highest negative predictive value (90%).ConclusionsIMA has evolved as a cost effective, highly sensitive, early diagnostic marker of cardiac ischemia and an earlier rule out test in AMI patients.