CD44/CD24 immunophenotypes on clinicopathologic features of salivary glands malignant neoplasms

Abstract Background Salivary Glands Malignant Neoplasms (SGMNs) account for 3-6% of head and neck cancers and 0.3% of all cancers. Tumor cells that express CD44 and CD24 exhibit a stem-cell-like behavior. CD44 is the binding site for hyaluronic acid, and CD24 is a receptor that interacts with P-selectin to induce metastasis and tumor progression. The present study aims to evaluate the expression of CD44 and CD24 on SGMNs and correlated these data with several clinicopathologic features. Methods Immunohistochemical stains for CD44 and CD24 were performed on tissue microarrays containing SGMN samples from 69 patients. The CD44, CD24 and CD44/CD24 expression phenotypes were correlated to patient clinicopathologic features and outcome. Results CD44 expression was associated with the primary site of neoplasm (p = 0.046). CD24 was associated with clinical stage III/IV (p = 0.008), T stage (p = 0,27) and lymph node (p = 0,001). The CD44/CD24 profiles were associated with the primary site of injury (p = 0.005), lymph node (p = 0.011) and T stage (p = 0.023). Univariate analysis showed a significant relationship between clinical staging and disease- free survival (p = 0.009), and the overall survival presents relation with male gender (p = 0.011) and metastasis (p = 0.027). Conclusion In summary, our investigation confirms that the clinical stage, in accordance with the literature, is the main prognostic factor for SGMN. Additionally, we have presented some evidence that the analysis of isolated CD44 and CD24 immunoexpression or the two combined markers could give prognostic information associated to clinicopathologic features in SGMN. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1284611098470676.

Polymorphous low-grade adenocarcinoma: an analysis of epidemiological studies and hints for pathologists

Abstract Background This study is an analysis of the prevalence of polymorphous low grade adenocarcinoma (PLGA) in epidemiological surveys of salivary tumors published in the English language from 1992 to 2012. Methods These surveys included studies from different researchers, countries and continents. The 57 surveys for which it was possible to calculate the percentage of PLGAs among all malignant minor salivary gland tumors (MMSGT) were included in this review. Results The statistical analyses show significant differences in the PLGA percentage by time period, country and continent in the studies included in this review. The percentage of PLGAs among MMSGTs varied among the studies, ranging from 0.0% to 46.8%. PLGA rates have varied over the period studied and have most recently increased. The frequency of reported PLGA cases also varied from 0.0% to 24.8% by the country in which the MMSGT studies were performed. The PLGA percentages also varied significantly by continent, with frequencies ranging from 3.9% in Asia to 20.0% in Oceania Conclusion Based on these results, we concluded that although the accuracy of PLGA diagnoses has improved, they remain a challenge for pathologists. To facilitate PLGA diagnoses, we have therefore made some suggestions for pathologists regarding tumors composed of single-layer strands of cells that form all of the histological patterns present in the tumor, consistency of the cytological appearance and uniformly positive CK7, vimentin and S100 immunohistochemistry, which indicate a single PLGA phenotype. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1059098656858324

The phenotype of Floating-Harbor syndrome: clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Background Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome. Methods and results Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from 2 to 52 years. The facial phenotype and expressive language impairments were defining features within the group. Height measurements were typically between minus two and minus four standard deviations, with occipitofrontal circumferences usually within the average range. Thirty-three of the subjects (63%) had at least one major anomaly requiring medical intervention. We did not observe any specific phenotype-genotype correlations. Conclusions This large cohort of individuals with molecularly confirmed FHS has allowed us to better delineate the clinical features of this rare but classic genetic syndrome, thereby facilitating the development of management protocols.

A compound heterozygote SLC26A2 mutation resulting in robin sequence, mild limbs shortness, accelerated carpal ossification, and multiple epiphysial dysplasia in two Brazilian sisters. A new intermediate phenotype between diastrophic dysplasia and recessive multiple epiphyseal dysplasia

Mutations in solute carrier family 26 (sulfate transporter), member 2 (SLC26A2) gene result in a spectrum of autosomal recessive chondrodysplasias that range from the mildest recessive form of multiple epiphysial dysplasia (rMED) through the most common diastrophic dysplasia (DTD) to lethal atelosteogenesis type II and achondrogenesis IB. The clinical variability has been ascribed to quantitative effect of mutations of the sulfate transporter activity. Here we describe two Brazilian sisters, born to healthy and non consanguineous parents, with Robin sequence, mild shortening of upper and lower limbs, brachymetacarpalia/tarsalia, additional and accelerated carpal ossification, marked genu valgum, and multiple epiphysial dysplasia. This phenotype was intermediate between DTD and rMED, and both girls have a compound heterozygous mutations for the SLC26A2, a Finnish founder mutation (c.-26?+?2T>C), and R279W. This combination of mutations has been observed in individuals with different phenotypes, including DTD, DTD variant, and rMED. The distinct phenotype of our cases reinforces the hypothesis that other factors may be influencing the phenotype as previously suggested.

Altered phenotype and function of dendritic cells in individuals with chronic periodontitis

OBJECTIVE: To investigate the effects of periodontal bacterial lysates on maturation and function of mature monocyte-derived dendritic cells (m-MDDCs) derived from individuals with chronic periodontitis (CP) or healthy periodontal tissue (HP). DESIGN: m-MDDCs derived from peripheral blood monocytes, cultured for 7 days in presence of interleukin (IL)-4 and granulocyte-macrophage colony stimulating factor (GM-CSF), were stimulated with lysates of Streptococcus sanguinis, Prevotella intermedia, Porphyromonas gingivalis, or Treponema denticola on day 4, and were then phenotyped. IL-10, IL-12 and IFN-gamma concentration in the supernatant of cultures were measured. RESULTS: Expression of HLA-DR was lower in bacterial-unstimulated mature m-MDDC from CP compared to HP (p=0.04), while expression of CD1a and CD123 were higher in CP. The expression pattern of HLA-DR, CD11c, CD123, and CD1a did not change on bacterial stimulation, regardless of the bacteria. Stimulation with P. intermedia upregulated CD80 and CD86 in CP cells (p≤0.05). Production of IL-12p70 by bacterial-unstimulated m-MDDCs was 5.8-fold greater in CP compared to HP. Bacterial stimulation further increased IL-12p70 production while decreasing IL-10. Significantly more IFN-gamma was produced in co-cultures of CP m-MDDCs than with HP m-MDDCs when cells were stimulated with P. intermedia (p=0.009). CONCLUSIONS: Bacterial-unstimulated m-MDDC from CP exhibited a more immature phenotype but a cytokine profile biased towards proinflammatory response; this pattern was maintained/exacerbated after bacterial stimulation. P. intermedia upregulated co-stimulatory molecules and IFN-gamma expression in CP m-MDDC. These events might contribute to periodontitis pathogenesis

Wilson’s disease in Southern Brazil: genotype-phenotype correlation and description of two novel mutations in ATP7B gene

OBJECTIVE: Wilson's disease (WD) is an inborn error of metabolism caused by abnormalities of the copper-transporting protein encoding gene ATP7B. In this study, we examined ATP7B for mutations in a group of patients living in southern Brazil. METHODS: 36 WD subjects were studied and classified according to their clinical and epidemiological data. In 23 subjects the ATP7B gene was analyzed. RESULTS: Fourteen distinct mutations were detected in at least one of the alleles. The c.3207C>A substitution at exon 14 was the most common mutation (allelic frequency=37.1%) followed by the c.3402delC at exon 15 (allelic frequency=11.4%). The mutations c.2018-2030del13 at exon 7 and c.4093InsT at exon 20 are being reported for the first time. CONCLUSION: The c.3207C>A substitution at exon 14, was the most common mutation, with an allelic frequency of 37.1%. This mutation is the most common mutation described in Europe.