Prognostic Value of BCL2 in Women Patients with Invasive Breast Cancer

Background: Breast cancers are heterogeneous, making it essential to recognize several biomarkers for cancer outcome predictions especially in young women where the classical prediction parameters are not suitable. The goal from this study is to evaluate the impact of B cell lymphoma 2 (BCL2), P53 and Ki-67 proteins expression on survival in young women patients with invasive ductal carcinoma. Patients and methods: Samples and clinical data from 238 patients were collected between 2003 and 2017. They were selected according to 2 criteria: age ≤40 years old and most of them are affected by an Invasive Ductal Carcinoma. We evaluated BCL2, P53 and ki-67 expression by immunochemistry test, and then we assessed correlations of these biomarkers expression with patient's clinicopathological characteristics and survival. Results: Triple negative breast cancer group showed a high frequency among our cohort but we emphasize an almost equitable distribution among all molecular groups. Contrary to other studies which reported that luminal A was correlated with better prognosis, our analysis demonstrated that luminal A is correlated with the Scarff, Bloom and Richardson (SBR) grading 2 or SBR grading 3. To better investigate the prognosis, we analyze three biomarkers known by their impact on physiopathology behavior on breast cancer BCL2, ki-67and P53. BCL2 is the more relevant one, it was correlated with molecular subtypes (p=0.0012) and SBR grading (p=0.0016). BCL2 seems to be the good prognostic biomarker related to survival (p=0.004) with a protective role among patients when endocrine therapy is not provided and Lymph Node (LN) involvement is positive (p=0.021, p=0.000 respectively). Conclusions: The classical prognostic parameters based mainly on the molecular classification in breast cancer seem insufficient in the case of young women. BCL2 protein expression analysis provides a better prognostic value. BCL2 should be clinically associated in current practice when young women specimens are diagnosticated.

Conduction mechanism, impedance spectroscopic investigation and dielectric behavior of La0.5Ca0.5-xAgxMnO3 manganites with compositions below the concentration limit of silver solubility in perovskites (0 ≤ x ≤ 0.2).

This study presents the electrical properties, complex impedance analysis and dielectrical behavior of La0.5Ca0.5-xAgxMnO3 manganites with compositions below the concentration limit of silver solubility in perovskites (0 ≤ x ≤ 0.2). Transport measurements indicate that all the samples have a semiconductor-like behavior. The metal-semiconductor transition is not observed across the whole temperature range explored [80 K-700 K]. At a specific temperature, a saturation region was marked in the σ (T) curves. We obtained a maximum σdc value at ambient temperature with the introduction of 20% Ag content. Two hopping models were applied to study the conduction mechanism. We found that activation energy (Ea) related to ac-conductivity is lower than the Ea implicated in dc-conductivity. Complex impedance analysis confirms the contribution of grain boundary to conductivity and permits the attribution of grain boundary capacitance evolution to the temperature dependence of the barrier layer width. From the temperature dependence of the average normalized change (ANC), we deduce the temperature at which the available density of trapped charge states vanishes. Such a temperature is close to the temperature at which the saturation region appears in σ(T) curves. Moreover, complex impedance analysis (CIA) indicates the presence of electrical relaxation in materials. It is noteworthy that relaxation species such as defects may be responsible for electrical conduction. The dielectric behavior of La0.5Ca0.5-xAgxMnO3 manganites has a Debye-like relaxation with a sharp decrease in the real part of permittivity at a frequency where the imaginary part of permittivity (ε'') and tg δ plots versus frequency demonstrate a relaxation peak. The Debye-like relaxation is explained by Maxwell-Wagner (MW) polarization. Experimental results are found to be in good agreement with the Smit and Wijn theory.

MECP2 is highly mutated in X-linked mental retardation.

Following the recent discovery that the methyl-CpG binding protein 2 (MECP2) gene located on Xq28 is involved in Rett syndrome (RTT), a wild spectrum of phenotypes, including mental handicap, has been shown to be associated with mutations in MECP2. These findings, with the compelling genetic evidence suggesting the presence in Xq28 of additional genes besides RabGDI1 and FMR2 involved in non-specific X-linked mental retardation (MRX), prompted us to investigate MECP2 in MRX families. Two novel mutations, not found in RTT, were identified. The first mutation, an E137G, was identified in the MRX16 family, and the second, R167W, was identified in a new mental retardation (MR) family shown to be linked to Xq28. In view of these data, we screened MECP2 in a cohort of 185 patients found negative for the expansions across the FRAXA CGG repeat and reported the identification of mutations in four sporadic cases of MR. One of the mutations, A140V, which we found in two patients, has been described previously, whereas the two others, P399L and R453Q, are novel mutations. In addition to the results demonstrating the involvement of MECP2 in MRX, this study shows that the frequency of mutations in MECP2 in the mentally retarded population screened for the fragile X syndrome is comparable to the frequency of the CGG expansions in FMR1. Therefore, implementation of systematic screening of MECP2 in MR patients should result in significant progress in the field of molecular diagnosis and genetic counseling of mental handicap.