The Intracellular Localization of ID2 Expression Has a Predictive Value in Non Small Cell Lung Cancer

ID2 is a member of a subclass of transcription regulators belonging to the general bHLH (basic-helix-loophelix) family of transcription factors. In normal cells, ID2 is responsible for regulating the balance between proliferation and differentiation. More recent studies have demonstrated that ID2 is involved in tumor progression in several cancer types such as prostate or breast

Expression of Aquaporin 5 (AQP5) Promotes Tumor Invasion in Human Non Small Cell Lung Cancer

The aquaporins (AQP) are water channel proteins playing a major role in transcellular and transepithelial water movement. Recently, the role of AQPs in human carcinogenesis has become an area of great interest. Here, by immunohistochemistry (IHC), we have found an expression of AQP5 protein in 35.3% (IHC-score: ≥1, 144/408) of the resected NSCLC tissue samples. Cases with AQP5-positive status (IHC-score: ≥2) displayed a higher rate of tumor recurrence than negative ones in NSCLC (54.7% vs. 35.1%, p = 0.005) and worse disease-free survival (p = 0.033; OR = 1.52; 95%CI:1.04−2.23). Further in vitro invasion assay using BEAS-2B and NIH3T3 cells stably transfected with overexpression constructs for full length wild-type AQP5 (AQP5) and its two mutants, N185D which blocks membrane trafficking and S156A which blocks phosphorylation on Ser156, showed that AQP5 induced cell invasions while both mutants did not. In BEAS-2B cells, the expression of AQP5 caused a spindle-like and fibroblastic morphologic change and losses of cell-cell contacts and cell polarity. Only cells with AQP5, not either of two mutants, exhibited a loss of epithelial cell markers and a gain of mesenchymal cell markers. In a human SH3-domains protein array, cellular extracts from BEAS-2B with AQP5 showed a robust binding activity to SH3-domains of the c-Src, Lyn, and Grap2 C-terminal. Furthermore, in immunoprecipitation assay, activated c-Src, phosphorylated on Tyr416, showed a stronger binding activity to cellular extracts from BEAS-2B with AQP5 compared with N185D or S156A mutant. Fluorescence in situ hybridization (FISH) analysis failed to show evidence of genomic amplification, suggesting AQP5 expression as a secondary event. Based on these clinical and molecular observations, we conclude that AQP5, through its phosphorylation on Ser156 and subsequent interaction with c-Src, plays an important role in NSCLC invasion and, therefore, may provide a unique opportunity for developing a novel therapeutic target as well as a prognostic marker in NSCLC

Cytology for pathologists: two sides of the same coin or different views of the same side?

Whereas cytology is a branch of pathology and cytopathology services are generally included in the departments and laboratories of pathology, there is often quite a sharp division between surgical pathology and cytology. These traditional divisions reflect different techniques, different problems, different attitudes and sometimes different commitments. Nonetheless these same divisions are becoming less sharp, and more and more artificial. In fact while it was clear since the beginning that cytopathology, and fine needle cytology above all, cannot be performed without a good knowledge of its histopathological bases and the application of ancillary techniques used on corresponding histopathology samples, the awareness of the need for a cytological background among histopathologists is more recent. The size of the samples submitted to the surgical pathology services are smaller and smaller and the applied diagnostic criteria are often more cytological than histological. Even some technical procedures originally specific for the two branches, such as small biopsies and cell blocks or fine needle aspirate smears and cytological scrapings of surgical samples, may be hardly distinguishable. Finally, pushed by clinicians, even the more reluctant histopathologists are often forced to perform diagnoses on cytological samples. For instance, lung pathology is often represented by cytological samples only and important therapeutic decisions on thyroid, breast or other organs are often taken on the basis of cytological reports only. In spite of this, cytopathology is not always exhaustively taught in pathology residencies and postgraduate courses. This tutorial was organized as an attempt to respond to these specific problems and needs. It was organized in three sections, which dealt with the cytopathology of breast, thyroid and lymph nodes. Each section started with a background lecture; then a large and varied selection of paradigmatic cases were shown by the tutors using glass slides and live microscopic projection combined with other imaging and relevant clinical data, followed by discussion. Principal and infrequent pathological entities have been shown, along with their cytological presentations, the diagnostic algorithms, the usage of ancillary techniques and the cyto-histological correlations. Attendees were invited to contribute to the diagnoses in a relaxed atmosphere. They were encouraged to take part in the discussion, focusing on differential diagnoses, the possibilities and limitations of cytology in the specific cases and the clinical implications. To ensure that all the attendees had the opportunity to participate interactively, the tutorial was offered to a limited number of participants. Digital copies of the introductory lectures and a final diploma from the European School of Pathology (ESoP) were issued to the participants. Organizers received excellent feedbacks and future tutorials will be scheduled in the next years

Juggling the COVID-19 pandemic: A cytopathology point of view

Since its first identification in China at the end of 2019, severe acute respiratory syndrome coronavirus 2 has rapidly spread all over the world, becoming an international healthcare emergency. In the era of coronavirus disease-2019 (COVID-19), several aspects of normal life, including those related to the medical activities, have been radically changed. Extraordinary measures have been adopted by different nations to cope with the rapid diffusion of COVID-19 all over the world. In hospitals, careful attention has been paid to manage infected patients with a possible detrimental effect for patients affected by other diseases. As with other medical fields, cytopathology laboratories have also drastically modified their activities to cope with the COVID-19 healthcare emergency. Here, the main effects of COVID-19 pandemic on the routine practice of cytopathology are summarised, focusing on the prioritisation policy adopted by cytopathologists worldwide

Peroxisome proliferator-activated receptor-gamma ligands as cell-cycle modulators

The peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors, initially described as molecular targets for compounds which induce peroxisomal proliferation. PPAR-gamma, the best characterized of the PPARs, is a ligand-activated transcription factor and a key regulator of adipogenic differentiation and glucose homeostasis. PPAR-gamma ligands have recently been demonstrated to affect proliferation, differentiation and apoptosis of different cell types. Recent in vitro and in vivo studies suggest the importance of specific PPAR-gamma ligands as cell-cycle modulators, establishing their antineoplastic properties. In this review, the latest knowledge on the role of PPAR-gamma ligands as cell-cycle modulators is presented, discussing also their role in cell proliferation, apoptosis and cancer. (C) 2004 Elsevier Ltd. All rights reserved