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.

The value of PAX8 and WT1 molecules in ovarian cancer diagnosis.

PAX8 and WT1 are transcription factors, each of them with distinct roles in organogenesis, morphogenesis, cell growth, and differentiation. Recently, their expression was also confirmed in a variety of malignancies, being included in the antibodies panel recommended for the female genital tract pathology. The aim of our study was to evaluate PAX8 and WT1 in different types of ovarian cancer (OC) with focus on (i) the completion of evidences of the Müllerian origin and (ii) the establishment of primary ovarian tumor status vs. metastasis. The study group consisted of 86 cases, with histopathological diagnosis covering the main subtypes of OC (low- and high-grade serous, low- and high-grade endometrioid, clear cell, mucinous, malignant Brenner tumor, malignant mixed Müllerian tumor, undifferentiated, and borderline). The investigation was based on immunohistochemical examination, performed by using specific antibodies applied on blocks obtained through Tissue MicroArray technique, and interpreted by scores assessing the nuclear positivity of tumoral cells. One case was not valuable due to technical difficulties. PAX8 expression was positive in 70 (81.39%) cases, the remaining 15 (17.44%) negative cases suggesting a non-Müllerian origin. WT1 expression was positive in 61 (71%) cases, mainly expressed in serous carcinoma, regardless of their differentiation degree, and negative in 24 (27%) cases. Our study provide supplementary evidences to support the association of PAX8 and WT1 immunostaining in the investigation of the complex biology of OC, PAX8 confirming the ovarian primary and WT1 allowing the refinement of the diagnosis in phenotype overlapping cases.

CLDN3 expression and significance - breast carcinoma versus ovarian carcinoma.

Claudins (CLDNs) are transmembrane proteins, as normal constituents of the architecture of tight junctions. Recent studies support their involvement in carcinogenesis, as changes in CLDNs structure result in alterations in tight junctions' structure and function, facilitating malignant transformation. We aimed CLDN3 investigation in both breast and ovarian carcinoma, targeting the identification of its expression differences. The immunohistochemical assessment was performed on 20 cases of breast carcinomas (Group 1) and 19 cases of epithelial ovarian carcinomas (Group 2). Firstly, the specific panel for the molecular classification was applied for specimens of the first group. Then, all the specimens were immunostained for CLDN3 and a semi-quantitative evaluation was made, based on the percentage of positive cells and the intensity of staining. In Group 1, in the ER positive category, CLDN3 was overexpressed in five cases (four cases of luminal A and one case of luminal B subtype, respectively), negative in three cases (luminal A subtype) and weakly expressed in a single case (luminal A subtype); in ER negative category, CLDN3 expression was strong in four cases (one case of Her2/neu subtype and three cases of basal-like subtype), negative in two cases (normal breast-like subtype) and weak in five cases (one case of Her2/neu subtype, one triple-negative subtype, and three basal-like subtype). In Group 2, CLDN3 was overexpressed in 15 cases, histopathologically diagnosed as serous (10 cases), mucinous (two cases), endometrioid (two cases), and mixed carcinomas (one case); a weak expression was noticed in a single case, of the serous subtype; CLDN3 was undetectable in three cases (one serous, one clear cell, and one endometrioid type). Our comparative analysis of CLDN3 profile in breast and ovarian cancer clearly indicates organ specificity.

Validation of PCR-RFLP techniques for the evaluation of codon 72 of p53 and CYP1A1 gene's polymorphisms in relation with ovarian cancer in a Romanian population.

Epidemiological studies suggest that the onset and progression of ovarian cancer are associated with the presence of estrogens. CYP1A1 gene has two polymorphisms, which may affect the estrogens' metabolites and contribute to increased susceptibility to neoplastic transformation of ovarian cells. P53 is a tumor suppressor gene, which acts to preserve stability of human genome. Codon 72 polymorphism of p53 gene was correlated with susceptibility for ovarian cancer. The aim of our study was to validate the use of PCR-RFLP techniques for the evaluation of p53 codon 72 and CYP1A1 gene polymorphisms in relation with ovarian cancer in a Romanian population and to evaluate gene-environment interaction in this context. The case-control study included 42 subjects. The assessment of risk and protective factors was performed using a questionnaire. Polymorphisms of CYP1A1 and p53 genes were assessed using the validated PCR-RFLP techniques. The statistical analysis was performed using Epi Info 3.5.1 software. Frequency of Arg/Arg genotype of p53 gene was higher among cases (43%) compared with controls (33.3%), but the difference was not statistically significant (p=0.75). The presence of Ile/Val polymorphism of CYP1A1 gene was identified in 9.5% of the cases and the MspI polymorphism of CYP1A1 gene was not identified in our subjects. Validation of techniques consisted in the optimization of RFLP methods for p53 and CYP1A1 genes polymorphism analyzing that allowed highlighting the existence of codon 72 polymorphism of p53 gene and Ile/Val polymorphism of CYP1A1 gene in the population from this region.

Healing process and laser therapy in the superficial periodontium: a histological study.

AIM: To evaluate the efficiency of laser therapy in healing, regeneration and repair processes located in the superficial periodontium after gingivectomy procedures. MATERIALS AND METHODS: The study group consisted of 38 patients without any systemic diseases presenting with gingival hypertrophy developed exclusively within the clinical context of gingivitis and/or periodontitis. All patients were included in the study based on their informed consent. All patients required several surgical interventions at the level of the superficial periodontium. Subgroup 1 (17 patients) was treated only through gingivectomy procedures. For subgroup 2 (21 patients), the gingivectomy was associated with laser therapy, applied every day for seven days. Gingival mucosa fragments were taken on day 1 (curative gingivectomy) and on day 21 (clinical control and corrective gingivectomy), and routinely processed for the microscopic exam, using Hematoxylin-Eosin and special stains (trichrome Szekely and Periodic Acid-Schiff). RESULTS AND DISCUSSION: The comparison between the morphological pictures characterizing the healing process associated or not with laser therapy, allowed the identification of some features supporting the benefits of laser therapy. We believe that the decrease in the inflammatory infiltrate located in the lamina propria is the critical morphological trait for the control of a healing process as near to restitutio ad integrum as possible. The diminished number of lymphocytes and macrophages will implicitly determine a lower production of chemical mediators interfering with the sequences of the healing process. CONCLUSIONS: The morphological differences identified at the gingival epithelium level and subjacent lamina propria support the value of laser therapy, stimulating an improved healing of the damaged tissues.

[Macroscopic and microscopic lesions in bronchial asthma]. / Aspecte lezionale macroscopice si microscopice în astmul bronsic.

Bronchial asthma is a chronic inflammatory disease characterized by reversible airways obstruction, inflammation, and increased bronchial hyperresponsivennes. The aim of this study was to evaluate the macroscopic and microscopic airways lesions, using bronhoscopy followed by biopsy in 38 cases of Outpatient Department from Clinic of Pulmonary Diseases Iasi, investigated between January 2005 - June 2008. Patients distribution according to the degree of severity was performed, using the international recommendations for asthma management of the Global Initiative for Asthma (GINA): intermittent (n=7 patients), mild persistent (n=10 patients), moderate persistent (n=16 patients), and severe persistent (n=5 patients). 23,68% of patients had a chronic disease of more than 15 years. The endoscopic changes of the peripheral airways were represented by edema, congestion, bronchial stenosis and mucus hypersecretion. Microscopic routine exam showed epithelial lesions (epithelial desquamation, goblet cell hyperplasia, squamous metaplasia), basement membrane thickening, edema, increased vascularisation, glandular and muscular hypertrophy and bronchial inflammatory infiltrate. Although bronhoscopy exam offers important information regarding changes of the airway mucosa in bronchial asthma, it concomitantly provide bioptic control, as microscopic examination still represents the "gold standard" assessment of bronchial wall remodeling process.