PTEN Loss as a Predictor of Tumor Heterogeneity and Poor Prognosis in Patients With EGFR-mutant Advanced Non-small-cell Lung Cancer Receiving Tyrosine Kinase Inhibitors

Background: Rapid disease progression of patients with advanced epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) has been recently associated with tumor heterogeneity, which may be mirrored by coexisting concomitant alterations. The aim of this analysis was to investigate the correlation between loss of function of PTEN and the efficacy of tyrosine kinase inhibitors in this population. Materials and Methods: Archival tumor blocks from patients with EGFR-mutant NSCLC who were administered upfront tyrosine kinase inhibitors were retrospectively collected. The status of 4 genes (PTEN, TP53, c-MET, IGFR) was evaluated by immunohistochemistry, and it was correlated with overall response rate, overall survival (OS), and progression-free survival (PFS). Results: Fifty-one patients were included. In multivariate analysis, PTEN loss (hazard ratio [HR], 3.46; 95% confidence interval [CI], 1.56-7.66; P = .002), IGFR overexpression (HR, 2.22; 95% CI, 1.03-4.77; P = .04), liver metastases (HR, 3.55; 95% CI, 1.46-8.65; P = .005), and Eastern Cooperative Oncology Group performance status (ECOG PS) > 1 (HR, 2.57; 95% CI, 1.04-6.34; P = .04) were significantly associated with shorter PFS. Patients with PTEN loss had a median PFS of 6 months (2-year PFS, 11.6%), whereas patients without PTEN loss had a median PFS of 18 months (2-year PFS, 43.6%) (log-rank P < .005). In the multivariate analysis, PTEN loss (HR, 5.92; 95% CI, 2.37-14.81; P < .005), liver metastases (HR, 2.63; 95% CI, 1.06-6.51; P = .037), and ECOG PS > 1 (HR, 2.80; 95% CI, 1.15-6.81; P = .024) were significantly associated with shorter OS. Patients with PTEN loss had a median OS of 6 months (2-year OS, 12.2%), whereas in patients without PTEN loss, OS was not reached (2-year OS, 63.9%) (log-rank P < .0005).Conclusions: A low-cost and reproducible immunohistochemistry assay for PTEN loss analysis represents a potential tool for identifying tumor heterogeneity in patients with advanced EGFR-mutant NSCLC

Estudo comparado da morfologia externa de Zaretis itys itylus (Westwood) e Agrias claudina annetta (Gray) (Lepidoptera, Nymphalidae, Charaxinae) I. Cabeça, apêndices e região cervical Comparative study of the external morphology of Zaretis itys itylus (Westwood) and Agrias claudina annetta (Gray) (Lepidoptera, Nymphalidae, Charaxinae). I. Head, appendages and cervical region

Realizou-se um estudo detalhado e comparado da morfologia externa da cabeça, apêndices e região cervical, de duas espécies de Charaxinae, Zaretis itys itylus (Westwood, 1850) e Agrias claudina annetta (Gray, 1832). Os resultados obtidos foram comparados com outros já publicados e relacionados com morfologia externa de outras subfamílias de Nymphalidae (Brassolinae, Morphinae, Danainae e Ithomiinae).<br>Two species of Charaxinae, Zaretis itys itylus (Westwood, 1850) and Agrias claudina annetta (Gray, 1832) were subject of a detailed and comparative study of external morphology of the head, appendages and cervical region. The results obtained were compared with other studies published and related to the external morphology of other Nymphalidae subfamilies (Brassolinae, Morphinae, Danainae and Ithomiinae)

To obtain more with less cytologic samples with ancillary molecular techniques-the useful role of liquid-based cytology

Context.-Fine-needle aspiration cytology has been increasingly used as the first tool in the evaluation of several diseases. Although cytology has a relevant role in the discrimination between benign and malignant lesions, conventional slides cannot lead to 100% conclusive results. It was hoped that the introduction of liquid-based cytology (LBC) would improve the efficacy of cytology through standardization, quality improvement, and the possibility of carrying out ancillary techniques on the residual stored material. In recent decades, the application of genomic alterations has been studied on cytologic samples with feasible and reliable results. The molecular analysis offers a powerful aid to define the best clinical or surgical approaches and follow-up for patients. In recent years, the application of different ancillary techniques has been carried out on conventional slides even though LBC represents a useful additional and alternative method for molecular testing. Objective.-To demonstrate the relevance of LBC as a valid aid to overcoming the difficulties encountered in the application of ancillary techniques on conventional slides. Data Sources.-We examined and reviewed our experience with the application of ancillary techniques on LBC performed on different body sites. Conclusions.-We emphasize that LBC achieves significant and accurate results. It represents a valid method for cytologic evaluation and it provides highly reproducible and informative molecular yields

The evaluation of miRNAs on thyroid FNAC: the promising role of miR-375 in follicular neoplasms

Fine needle aspiration cytology (FNAC) plays an essential role in the evaluation of thyroid nodules especially for the category of follicular neoplasms (FN) representing 25\ua0% of all thyroid cases including different neoplastic entities. Hence, one of the most promising areas is the application of molecular tests to FNAC. Among them, microRNAs (miRNA),identified as negative (post-transcriptional) gene expression regulators involved in tumor development, are likely to discriminate among FNs. Limited data explored the use of miRNAs on FNAC as well as their role in the malignant risk stratification. We aimed to define whether liquid-based cytology (LBC) is a valid method for miRNA evaluation. From June 2014 to March 2015, we enrolled 27FNs with histological follow-up. In the same reference period, 13 benign nodules (BN) and 20 positive for malignancy (PM) were selected as controls. Histologically, FNs resulted in 14 malignancies (3 papillary thyroid carcinoma-PTC and 11 follicular variant of PTC-FVPC) and 13 follicular adenomas (FA). The 20 PMs included two FVPC, 16 PTC and two medullary thyroid carcinoma (MTC). Five miRNAs (10b, 92a, 221/222 cluster, and 375) were studied on LBC and quantified by real-time PCR. Only miR-375 was over-expressed in the FNs diagnosed as carcinomas and in the PMs. A cut-off of 12 miR-375/U6 relative ratio recognized all BNs and 95\ua0% PMs. Specifically, in each category, FVPCs and PTCs did not show any difference while MTCs had the highest value. miR-375 shows 97.1\ua0% sensitivity, 100\ua0% specificity, 96.3\ua0% negative predictive value (NPV), 100\ua0% positive predictive value (PPV), and 98.3\ua0% diagnostic accuracy. LBC is suitable for miRNAs evaluation. miR-375 resulted over-expressed in all malignant FNs and 95\ua0% PMs. It may represent a valid aid in ruling out BNs and supporting PTCs and/or FVPCs

Morfologia externa de Thyridia psidii cetoides (Rosenberg & Talbot) (Lepidoptera, Nymphalidae, Ithomiinae). III. Abdome e apêndices External morphology of Thyridia psidii cetoides (Rosenberg & Talbot). III. Abdomen and appendages (Lepidoptera, Nymphalidae, Ithomiinae)

<abstract language="eng">A detailed study of the abdominal external morphology of both sexes of Thyridia psidii cetoides (Rosenberg & Talbot, 1914) is presented. The material for this research was obtained at the city's plant nursery "Horto Florestal de Curitiba", Paraná, Brazil; mainly by rearing eggs and larvae collected on Cyphomandra betacea (Canavilles) Sendtner, 1845 (Solanaceae). When possible, the results obtained were compared with those already available in the literature concerning other Nymphalidae subfamilies morphology (Brassolinae, Morphinae and Danainae); the most striking feature being the asymmetrical valvae of the male and the length and faint sclerotinization of the third abdominal sternite in both sexes. A resume containing the main morphological differences to other nymphalid subfamillies, found throughout this research concerning head, thorax and abdome, is presented

Morfologia externa do adulto de Almeidaia aidae Mielke & Casagrande (Lepidoptera, Saturniidae, Arsenurinae, Almeidaiini). III. Abdome External morphology of Almeidaia aidae Mielke & Casagrande (Lepidoptera, Saturniidae, Arsenurinae, Almeidaiini). III. Abdome

A morfologia externa do abdome do adulto de Almeidaia aidae Mielke & Casagrande, 1981 é descrita e ilustrada pela primeira vez. Os resultados obtidos foram comparados com outras espécies de Saturniidae. É uma espécie rara e endêmica da região do Cerrado. Estudos sobre sua biologia foram publicados pelo quarto autor. Esta é a terceira contribuição sobre a morfologia da espécie tendo sido as anteriores sobre a cabeça e o tórax.<br>The external morphology of adult abdome of Almeidaia aidae Mielke & Casagrande, 1981 is described and illustrated for the first time. The results obtained were compared with others species of Saturniidae. This species is rare and endemic of the Cerrado region. Biological studies were published by the fourth author. This is the third of a series of papers about the species, the previous two were about head and thorax morphology

Morphology combined with ancillary techniques: An algorithm approach for thyroid nodules

Several authors have underlined the limits of morphological analysis mostly in the diagnosis of follicular neoplasms (FN). The application of ancillary techniques (AT), including immunocytochemistry(ICC) and molecular testing (MT), contributes to a better definition of the risk of malignancy(ROM) and management of FN. According to literature, the application of models, including the evaluation of ICC, somatic mutations (i.e. BRAFV600E ), miRNA analysis is proposed for FNs. This study discusses the validation of a diagnostic algorithm in FN with a special focus on the role of morphology then followed by AT