Alfredo Ribeiro Da Silva

Immunohistochemical features of claudin-low intrinsic subtype in metaplastic breast carcinomas.

PURPOSEnThe claudin-low molecular subtype of breast cancer includes triple negative invasive carcinomas, with a high frequency of metaplastic and medullary features. The aim of this study was to evaluate the immunohistochemistry expression of claudins in a series of metaplastic breast carcinomas. We also assessed other claudin-low features, such as the cancer stem cell-like and epithelial-to-mesenchymal transition phenotypes.nnnRESULTSnThe majority of the cases showed weak or negative staining for membrane claudins expression. We found 76.9% (10/13) low expressing cases for claudin-1, 84.6% (11/13) for claudin-3 and claudin-4, and 92.3% (12/13) for claudin-7. Regarding the cancer stem cell marker ALDH1, 30.8% (4/13) showed positive staining. We also showed that the majority of the cases presented a CD44(+)CD24(-/low) phenotype, positivity for vimentin and lack of E-cadherin expression. Interestingly, these claudin-low molecular features were specific of the mesenchymal component of metaplastic breast carcinomas, since its frequency was very low in other breast cancer molecular subtypes, as luminal, HER2-overexpressing and non-metaplastic triple negative tumors.nnnCONCLUSIONSnThe negative/low expression of claudins and E-cadherin, high levels of vimentin, and the breast cancer stem cell phenotype suggests that metaplastic breast carcinomas have similar features to the ones included in the claudin-low molecular subtype, specially their mesenchymal components.

Menopause Leading to Increased Vaginal Wall Thickness in Women with Genital Prolapse: Impact on Sexual Response

INTRODUCTIONnHypoestrogenism causes structural changes in the vaginal wall that can lead to sexual dysfunction. A reduction in vaginal wall thickness has been reported to occur after menopause, although without precise morphometry.nnnAIMnTo measure vaginal wall thickness in women with genital prolapse in normal and hypoestrogenic conditions and to correlate sexual dysfunction with vaginal wall thickness and estradiol levels.nnnMETHODSnSurgical vaginal specimens from 18 normoestrogenic and 13 postmenopausal women submitted to surgery for genital prolapse grades I and II were examined. Patients were evaluated for FSH, estradiol, prolactin, glycemia, and serum TSH levels. For histological analysis, samples were stained with Massons trichrome and hematoxylin-eosin. Sexual function was assessed by the Golombok-Rust Inventory of Sexual Satisfaction (GRISS).nnnMAIN OUTCOME MEASURESnGRISS questionnaire, histological analysis, morphometric methods, Massons trichrome.nnnRESULTSnThe vaginal wall was thicker in the postmenopausal than premenopausal group (2.72 +/- 0.72 mm and 2.16 +/- 0.43, P = 0.01, and 2.63 +/- 0.71 mm and 2.07 +/- 0.49 mm, P = 0.01, for the anterior and posterior walls, respectively). These thicknesses seem to be due to the muscular layer, which was also thicker in the postmenopausal group (1.54 +/- 0.44 and 1.09 +/- 0.3 mm, P = 0.02, and 1.45 +/- 0.47 and 1.07 +/- 0.44 mm, P = 0.03, for the anterior and posterior wall, respectively). The vaginal epithelium was thinner in the middle segment than in the proximal one in the posterior wall (0.17 +/- 0.07 mm, 0.15 +/- 0.05 mm, 0.24 +/- 0.09 mm, P = 0.02). There was no correlation between coital pain, vaginal wall thickness, and estradiol levels in either group.nnnCONCLUSIONnThe vaginal wall is thicker after menopause in women with genital prolapse. In this study, vaginal thickness and estrogen levels were not related to sexual dysfunction.

Assessing the maxillary sinus mucosa of rabbits in the presence of biodegradable implants

UNLABELLEDnIn an attempt to improve the quality of life of patients with vitreous humor disease, ophthalmologists began offering steroid-eluting biodegradable implants to their patients. These implants can be used as an alternative treatment for CRS and this is why this experimental study was carried out on rabbit maxillary sinuses.nnnOBJECTIVEnThis study aims to assess the histology of the mucosa of the maxillary sinuses of rabbits after the placement of a prednisolone-eluting biodegradable implant.nnnMETHODnEighteen rabbits were randomly divided into two groups: group 1 - subjects had drug-eluting implants placed on their left maxillary sinuses; group 2 - subjects had non-drug-eluting implants placed on their left maxillary sinuses. The right maxillary sinuses served as the controls. After seven, 14, and 28 days three rabbits in each group were randomly picked to have their tissue inflammatory response assessed.nnnRESULTSnLevels of mucosal inflammation were not significantly different between the groups with and without drug-eluting implants and the control group, or when the groups with drug-eluting implants and non-drug-eluting implants were compared.nnnCONCLUSIONnSigns of toxicity or mucosal inflammation were not observed in the maxillary sinuses of rabbits given prednisolone-eluting implants or non-drug-eluting implants.

Fulminant myocarditis and viral infection.

A 29-year-old woman with no previous cardiac history preented at the emergency room of a county ambulatory, Ribeirão reto, São Paulo state, Brazil, complaining of general malaise, ever, myalgia, and headache over the last three days. The physcal examination at that time was unremarkable. Laboratory tests howed a hematocrit of 38% and platelet count of 141,000/mm3. he was oriented to drink 2500 ml of liquids at home in the next wo days. At day 5 of infection, laboratory tests revealed an 11% ncrease in the hematocrit and platelet count of 113,000/m3. She eceived intravenous saline 0.9%, 2000 ml over 3 h, and was disharged home. At day 6 of infection, she returned to the emergency oom with a systemic pressure of 80 × 60 mmHg and no other bnormality in the physical examination. Three hours later, she eveloped mental obtundation, peripheral cyanosis, and undeectable systemic blood pressure. She received 2000 ml of saline

CHK2 Immunohistochemical Expression in Colon Cancer and its Relation with Clinicopathological Features and Outcome in Metastatic ColonCancer Patients

Background: The DNA damage checkpoint pathway has been of interest to the field of cancer biology, since checkpoint defects result in the accumulation of altered genetic information, a central feature of carcinogenesis. Little is known about the role that CHK2 (checkpoint kinase 2) gene plays in colorectal cancer tumorigenesis. The purpose of this study was to evaluate CHK2 expression in metastatic colon cancer and correlate it with clinicopathological features and patient survival. n Methods: Tissues of primary tumors were obtained from 58 patients with metastatic colon cancer. The tissue microarray immunohistochemistry was the technique used to evaluate CHK2 expression. Statistical analysis used was SPSS17; p-value was set at <0.050. The relationship between the CHK2 immunohistochemical expression and the patients’ clinical and pathological features as well as survival data was reported. nResults: CHK2 expression was positive in 69% of the cases. CHK2 expression was associated with lymph node status (p=0.012) and survival (p=0.034). Negative CHK2 expression increased the chance of lymph node involvement (Odds ratio: 10.23, p=0.03). The global survival time of CHK2-negative patients was higher (72 versus 59 months); the same trend emerged for progression-free survival time (19 versus 13 months). The survival curves differed depending on CHK2 expression in patients with or without lymph node involvement; survival was lower in CHK2-positive. A larger number of deaths occurred in CHK2-positive. Multivariate regression analysis identified performance status ECOG (p=0.01), synchronous metastasis (p=0.037), tumor cell differentiation (p=0.029) and CHK2 expression (p=0.020) as independent factors for overall survival. nConclusions: This study demonstrated that positive CHK2 expression in colon cancer indicates aggressiveness and impacts negatively patient survival and outcome. On the other hand, a negative expression indicates dissemination to lymph nodes.

Estrogen receptor expression and vessel density in the vagina wall in postmenopausal women with prolapse.

After menopause, critically estrogen low levels result in modifications in vaginal wall. This cross-sectional study aims to determine whether there is a change in the number of vessels in the lamina propria of the vagina after menopause in parallel to the ER-alpha expression on the vaginal wall. Twelve women who underwent a genital surgery for genital prolapse up to grade II were selected. They were divided into two groups: a premenopausal group (PG) consisting of six women who were 18-40 years old with FSH levels =12 mIU/ml and regular cycles, and a menopausal group (MG) consisting of six women at least one year after menopause who were <65 years old with FSH levels =40 mIU/ml. Slides were stained for ER-alpha immunohistochemistry, and an endothelial cell marker CD3 was used to label vessels which were identified by using a system for morphometry. The number of vessels was significantly higher in the PG than in the MG both on the anterior wall (PG: 1.055 ± 145.8 vessels/mm(2), MG: 346.6 ± 209.9 vessels/mm(2), p<0.0001) and on the posterior wall (PG: 1064 ± 303.3 vessels/mm(2), MG: 348.6 ± 167.3 vessels/mm(2), p=0.0005). The ER-alpha score was significantly higher in the PG than the score for the MG on both the anterior and posterior walls (PG: 6.0 ± 0.52, MG: 2.5 ± 0.89, p=0.007; PG: 5.8 ± 0.79, MG: 2.7 ± 0.95, p=0.03, respectively). There was a positive correlation between the ER-alpha score and the vessel concentration on the anterior (r=0.6656, p=0.018) and posterior (r=0.6738, p=0.016) vaginal walls. Age was strongly negatively correlated with vessel concentration on the vaginal walls (respectively r=-0.9033, p<0.0001, r=-0.7440, p=0.0055). Therefore, postmenopausal women with genital prolapse have a smaller number of vessels on the vaginal wall compared to normoestrogenic controls with the same pathological condition. Hypoestrogenism and advancing age are factors that are associated to these changes.

Tumor neuroendócrino primário de mama: relato de três casos e revisão de literatura

Os tumores neuroendocrinos primarios de mama (TNPMs) sao incomuns e nao ha consenso quanto a tratamento e prognostico. No presente trabalho, foram revisados os diagnosticos de 1.184 pacientes com câncer de mama atendidos no Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo (HCFMRP/USP), identificando tres casos que preenchiam os criterios de TNPM, segundo classificacao estabelecida pela Organizacao Mundial da Saude (OMS) em 2003. Foram avaliados os achados clinicopatologicos e imuno-histoquimicos e as terapias realizadas, buscando caracterizar os padroes histopatologicos e de comportamento distintos dos carcinomas convencionais de mama.

Abstract 1035: WAS/WASL interacting protein family, member 2 (WIPF2) expression in breast carcinomas

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FLnnERBB2 over-expression in breast carcinomas is associated with poor prognosis and early metastatic dissemination. The gene WIPF2 is located on the position q21.2 of the chromosome 17 between ERBB2 and TOP2A (17q21-q22) genes and encodes a WASP interacting protein (WIRE protein). It has been reported that this protein has a role in the WASP-mediated organization of the actin cytoskeleton. This protein is a potential link between the activated platelet-derived growth factor receptor and the actin polymerization machinery and its expression has never been evaluated in cancer tissues. The objectives of this investigation were the characterization of the levels of expression of WIPF2 gene in breast carcinomas and its correlation with EGFR 1 stimuli. Material and Methods: We studied the expression of WIRE protein in 87 ductal invasive carcinomas and WIPF2 gene in three breast cancer cell lines (Hb4a-C5.2, MCF7 and SKBR3). Breast cancer samples were mounted in a TMA block and the immunohistochemistry was performed to evaluate the expression of WIRE protein, estrogen receptor, progesterone receptor, HER-2 and Ki-67. The HER2, WIRE and KI-67 expression was further studied by using ImageScope software after digital image capture (Aperio). Tumors were classified according ER, PgR, HER2 and Ki-67 expression in luminal A or B, HER2 positive and basal-like subtypes. The WIPF2 and ERBB2 genes expression (real time RT-PCR) and WIRE protein (immunofluorescence) was analyzed in all cell lines before and after EGF treatment (40ng/µl for 12 and 72 hours). Results: We observed that WIRE protein is ubiquitously expressed in breast carcinomas. According to digital analysis, HER2 positive tumors have a higher expression of WIRE protein (p = 0.02). SKBR3 cell line (HER2 over expressed) has a significant 11 fold increase in WIPF2 gene expression comparing to MCF7. After EGF (EGFR 1 ligand) treatment, we observed a significant decrease in WIPF2 gene expression in SKBR3. Additionally, we observed a subcellular modification of WIRE protein, specially in SKBR3 cell line. The protein is usually dispersed into the cytoplasm. After EGF treatment, there is a reduction in its expression and the protein concentrate in endoplasmic reticulum (peri-nuclear). The decrease in WIPF2 gene expression and the subcellular protein modification is time dependent. They are more expressive after 72 hours of EGF exposure. Conclusion: WIRE protein is over-expressed in HER2 ductal breast carcinomas. EGF stimuli (EGFR1) changes its sub-cellular localization and reduces the WIPF2 gene expression in SKBR3 (HER2 positive) cell line. It is possible to infer that the expression of WIPF2 could be associated with ERFR signaling and the actin cytoskeleton motility.nnCitation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1035. doi:10.1158/1538-7445.AM2011-1035