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Medical Sciences	100%

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Distinguishing medullary carcinoma of the breast from high-grade hormone receptor-negative invasive ductal carcinoma: an immunohistochemical approach

HISTOPATHOLOGY, Issue 7 2010
Uta Flucke
Flucke U, Flucke M T, Hoy L, Breuer E, Goebbels R, Rhiem K, Schmutzler R, Winzenried H, Braun M, Steiner S, Buettner R & Gevensleben H (2010) Histopathology,56, 852,859 Distinguishing medullary carcinoma of the breast from high-grade hormone receptor-negative invasive ductal carcinoma: an immunohistochemical approach Aims:, Medullary carcinomas (MCs) represent a rare breast cancer subtype associated with a rather favourable prognosis compared with invasive ductal carcinomas (IDCs). Due to histopathological overlap, MCs are frequently misclassified as high-grade IDCs, potentially leading to overtreatment of MCs. Our aim was to establish novel diagnostic markers distinguishing MCs from hormone receptor-negative high-grade IDCs. Methods and results:, Sixty-one MCs and 133 hormone receptor-negative IDCs were analysed in a comparative immunohistochemical study. Applied markers included a comprehensive panel of cytokeratins (CKs), vimentin, smooth muscle actin (SMA), p63, p53, cell adhesion molecules [N-CAM (CD56), syndecan-1 (CD138), E-cadherin and P-cadherin] and development associated transcription factors (AP-2,, AP-2,). A significantly higher proportion of IDCs displayed increased expression of CK7, AP-2, and HER2 in contrast to MCs (CK7: 91% of IDCs versus 77% of MCs; AP-2,: 77% versus 57%; and HER2: 26% versus 7%, each P < 0.01). Vice versa, MCs were slightly more frequently positive for SMA and vimentin (P > 0.05). Conclusions:, Hormone receptor-negative high-grade IDCs are significantly associated with luminal differentiation, Her2 and AP-2, overexpression, whereas MCs tend to display myoepithelial features. Markers analysed in this study are of diagnostic value regarding the differential diagnosis of MCs. [source]

A multiplex immunoassay demonstrates reductions in gingival crevicular fluid cytokines following initial periodontal therapy

JOURNAL OF PERIODONTAL RESEARCH, Issue 1 2010
D. H. Thunell
Thunell DH, Tymkiw KD, Johnson GK, Joly S, Burnell KK, Cavanaugh JE, Brogden KA, Guthmiller JM. A multiplex immunoassay demonstrates reductions in gingival crevicular fluid cytokines following initial periodontal therapy. J Periodont Res 2009; doi: 10.1111/j.1600-0765.2009.01204.x. © 2009 John Wiley & Sons A/S Background and Objective:, Cytokines and chemokines play an important role in the pathogenesis of periodontal diseases. The objective of this study was to quantitatively assess the effect of initial periodontal therapy on gingival crevicular fluid levels of a comprehensive panel of cytokines and chemokines, including several less extensively studied mediators. Material and Methods:, Clinical examinations were performed and gingival crevicular fluid samples obtained from six subjects with generalized severe chronic periodontitis prior to initial periodontal therapy and at re-evaluation (6,8 weeks). Four diseased and two healthy sites were sampled in each subject. Twenty-two gingival crevicular fluid mediators were examined using a multiplex antibody capture and detection platform. Statistical analyses were performed by fitting mixed effects linear models to log-transformed gingival crevicular fluid values. Results:, Gingival crevicular fluid interleukin (IL)-1, and IL-1, were the only cytokines to differ in initially diseased vs. initially healthy sites. Following initial therapy, 13 of the 16 detectable cytokines and chemokines decreased significantly in diseased sites, including IL-1,, IL-1,, IL-2, IL-3, IL-6, IL-7, IL-8, IL-12 (p40), CCL5/regulated on activation, normally T cell expressed and secreted (RANTES), eotaxin, macrophage chemotactic protein-1, macrophage inflammatory protein-1, and interferon-,. At healthy sites, only three of the 16 mediators were significantly altered following therapy. Conclusion:, This is the first study, to our knowledge, to evaluate such an extensive panel of gingival crevicular fluid mediators within the same sample prior to and following initial therapy. The results confirm that periodontal therapy effectively reduces pro-inflammatory cytokines and chemokines, including less well-described mediators that may be important in initiation and progression of periodontitis. The multiplex assay will prove useful for future gingival crevicular fluid studies. [source]

ORIGINAL ARTICLE: Multiple Cytokine Profile in Plasma and Amniotic Fluid in a Mouse Model of Pre-Term Labor

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2009
Qing Yang
Problem, The rate of pre-term birth in the United States continues to rise despite several interventions. Induction of pro-inflammatory cytokines and chemokines has been implicated in the activation of the cascade of events resulting in pre-term labor. To date, no comprehensive panel of the cytokine profile in PTL has been published. Method of study, To address cytokine profiles in pre-term labor, levels of 19 plasma and amniotic fluid cytokines were measured using a multiplex immunoassay in an inflammation-induced murine model of pre-term labor. Results, Pro-inflammatory mediators, RANTES, KC, IL-6, and IL-12p40 were increased by 3 hr and remained high at 15 hr. Concentrations of KC, IL-6, IL-1,, and MIP-1, were increased in the amniotic fluid at 15 hr. Plasma levels of anti-inflammatory mediators IL-10 and IL-13 at 15 hr were unchanged and decreased respectively. Conclusion, These results suggest that stimulation of several pro-inflammatory cytokines occurs very early in the cascade of events and remains increased, whereas anti-inflammatory cytokines are either unchanged or decreased until the onset of delivery in an inflammation-induced mouse model of pre-term labor. [source]

Comprehensive flow cytometry phenotype in acute leukemia at diagnosis and at relapse

APMIS, Issue 5 2010
XIN LI
Li X, Du W, Liu W, Li X, Li H, Huang S-A. Comprehensive flow cytometry phenotype in acute leukemia at diagnostic and at relapse. APMIS 2010; 118: 353,59. Multiparameter flow cytometry (MFC) plays a vital role in the detection of minimal residual disease (MRD) and diagnosis of relapse in acute leukemia. However, application of a limited panel of antibodies in MFC leads to high rates of false-negative and false-positive results. Thirteen patients with acute lymphoblastic leukemia (ALL) and 12 patients with acute myeloid leukemia (AML) were immunophenotyped by MFC at diagnosis and at relapse using a comprehensive panel of monoclonal antibodies (McAbs) to 27 antigens and CD45/SSC gating. In 23 of 25 patients (92.3%), changes in at least one of progenitor-associated, myeloid and lymphoid antigens between diagnosis and relapse were observed. Antigen changes were observed in 92 of 239 antigens (38.5%) expressed in 25 patients, in 49 of 117 antigens (41.9%) expressed in 13 ALL patients, and in 43 of 122 antigens (35.2%) expressed in 12 AML patients. Phenotypic changes were characterized by the expression of cross-lineage antigens. The intralineage change was observed in the majority of patients. However, myeloid lineage shift was identified by MFC in two patients with T-ALL. Multiple panels of three or more McAbs are likely to be required in the monitoring of MRD and diagnosis of relapse in acute leukemia by MFC. [source]