AimsThe distinction between benign and malignant thyroid nodules has important therapeutic implications. Our objective was to develop an assay that could classify indeterminate thyroid nodules as benign or suspicious, using routinely prepared fine needle aspirate (FNA) cytology smears.MethodsA training set of 375 FNA smears was used to develop the microRNA-based assay, which was validated using a blinded, multicentre, retrospective cohort of 201 smears. Final diagnosis of the validation samples was determined based on corresponding surgical specimens, reviewed by the contributing institute pathologist and two independent pathologists. Validation samples were from adult patients (≥18 years) with nodule size >0.5 cm, and a final diagnosis confirmed by at least one of the two blinded, independent pathologists. The developed assay, RosettaGX Reveal, differentiates benign from malignant thyroid nodules, using quantitative RT-PCR.ResultsTest performance on the 189 samples that passed quality control: negative predictive value: 91% (95% CI 84% to 96%); sensitivity: 85% (CI 74% to 93%); specificity: 72% (CI 63% to 79%). Performance for cases in which all three reviewing pathologists were in agreement regarding the final diagnosis (n=150): negative predictive value: 99% (CI 94% to 100%); sensitivity: 98% (CI 87% to 100%); specificity: 78% (CI 69% to 85%).ConclusionsA novel assay utilising microRNA expression in cytology smears was developed. The assay distinguishes benign from malignant thyroid nodules using a single FNA stained smear, and does not require fresh tissue or special collection and shipment conditions. This assay offers a valuable tool for the preoperative classification of thyroid samples with indeterminate cytology.

Expression of Ki-67, a nuclear antigen protein present in all cycling cells, is used to determine the growth fraction of tumors. The aim of this study was to evaluate the role and prognostic significance of the Ki-67 proliferation index (PI) in non-Hodgkin's lymphoma. Ki-67 was assayed immunohistochemically in tissue samples of 319 patients with newly-diagnosed non-Hodgkin's lymphoma. In 268 patients, the Ki-67 PI was correlated with clinical course and outcome. The mean Ki-67 PI ranged from 26.6% in indolent lymphomas to 97.6% in very aggressive lymphomas (P < 0.001). The index was <45% in 82.8% of indolent lymphomas and >45% in 85% of aggressive lymphomas (AUC 5 0.877, P < 0.001). In patients with diffuse large B-cell lymphoma (n 5 141), a Ki-67 PI of 70% was found to significantly discriminate patients with good or bad prognosis (AUC 5 0.65, P 5 0.004). Three-year survival was 75% ± 5.6% in patients with a low Ki-67 index compared with 55.9% ± 6% in patients with a high index (P 5 0.015). In patients with a low IPI (≤2), 3-year survival was 94% ± 4% in those with a Ki-67 index ≤70% and 64% ± 8.1% in those with a higher index (P 5 0.002); in patients with bulky disease (>10 cm), the corresponding 3-year survival by Ki-67 index was 100% and 25% ± 12% (P 5 0.012). Our results suggest that the mean Ki-67 PI differs by type of lymphoma. A cut-off value of 45% can help differentiate indolent from aggressive disease. In diffuse large B-cell lymphoma, a cut-off value of 70% can distinguish patients with a good and bad prognosis when combined with other prognostic factors of low IPI score and bulky disease. Am. J. Hematol. 84:338-343, 2009. V

We present the synthesis of reactive polymer brushes prepared by surface reversible addition–fragmentation chain transfer polymerization of pentafluorophenyl acrylate. The reactive ester moieties can be used to functionalize the polymer brush film with virtually any functionality by simple post‐polymerization modification with amines. Dithiobenzoic acid benzyl‐(4‐ethyltrimethoxylsilyl) ester was used as the surface chain transfer agent (S‐CTA) and the anchoring group onto the silicon substrates. Reactive polymer brushes with adjustable molecular weight, high grafting density, and conformal coverage through the grafting‐from approach were obtained. Subsequently, the reactive polymer brushes were converted with amino‐spiropyrans resulting in reversible light‐responsive polymer brush films. The wetting behavior could be altered by irradiation with ultraviolet (UV) or visible light. Furthermore, a patterned surface of polymer brushes was obtained using a lithography technique. UV irradiation of the S‐CTA‐modified substrates leads to a selective degradation of S‐CTA in the exposed areas and gives patterned activated polymer brushes after a subsequent RAFT polymerization step. Conversion of the patterned polymer brushes with 5‐((2‐aminoethyl)amino)naphthalene‐1‐sulfonic acid resulted in patterned fluorescent polymer brush films. The utilization of reactive polymer brushes offers an easy approach in the fabrication of highly functional brushes, even for functionalities whose introduction is limited by other strategies. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012