The transcription factor p53 is a tumor suppressor. As such, the P53 gene is frequently altered in human cancers. However, over 80% of the P53 mutations found in human cancers are missense mutations that lead to expression of mutant proteins that not only lack p53 transcriptional activity but exhibit new functions as well. Recent studies show that restoration of p53 expression leads to tumor regression in mice carrying p53 deletions. However, the therapeutic efficacy of restoring p53 expression in tumors containing p53 missense mutations has not been evaluated. Here we demonstrate that restoring wild-type p53 expression halted tumor growth in mice inheriting a p53 R172H missense mutation that is equivalent to a P53 missense mutation detected in approximately 6% of human cancers. However, it did not lead to tumor regression, as was observed in mice lacking p53. We further showed that the dominant-negative effect of the mutant p53 encoded by p53 R172H dampened the activity of the restored wild-type p53. We therefore conclude that in a mutant p53 background, p53 restoration has the therapeutic potential to suppress tumor progression. Our findings support using p53 restoration as a strategy to treat human cancers with P53 missense mutations and provide direction for optimizing p53 restoration in cancer therapy. IntroductionThe tumor suppressor p53 is a transcription factor. Upon activation by signals, such as DNA damage, oncogenic stimuli, and hypoxia, wild-type p53 activates the transcription of genes involved in apoptosis, cell cycle arrest, differentiation, and senescence (1, 2). These potent antitumor activities prevent cells with aberrant growth signals from proliferating. Approximately, half of human cancers have P53 gene alterations that result in loss of p53 activity. While a few of these alterations are P53-null mutations, over 80% are P53 missense mutations that lead to expression of mutant p53 proteins (3, 4). Many p53 missense mutants lack p53 transcriptional activity and show gain-of-function activities.In particular, the arginine-to-histidine mutation at codon 175 of the P53 gene (corresponding to p53 R172H in mice) occurs in about 6% of human cancers (5). The p53 R172H mutation has gain-of-function properties, manifested as a tumor metastasis phenotype in p53 R172H heterozygous mice that is lacking in p53 +/-mice (6, 7). Another property of the p53R172H mutant is its dominant-negative effect that silences wild-type p53 under some circumstances (8). Thus, for example, in response to γ-irradiation, mutant p53R172H inactivates wild-type p53 activities (9). Additionally, mutant p53 binds and suppresses the activities of the related proteins, p63 and p73 (7). However, the p53 R172H heterozygous mice that express equal amounts of wild-type and mutant p53 have survival curves identical to those of p53 +/-mice, indicating that

Social media use is very common and can be an effective way for professionals to discuss information and interact with colleagues. Twitter (Twitter, Inc, San Francisco, California) is a social media network where posts, termed tweets, are limited to 140 characters. Professional use of Twitter is ideal for physicians interested in both networking and education and is optimally used to facilitate in-person networking. Live-tweeting (posting real-time reactions to events) at professional meetings is also a popular and highly successful use of Twitter. Physicians report patient privacy as the top concern preventing use of social media for professional reasons, and although generally social media use is safe, it is essential to understand how to protect patient confidentially. Other social media platforms with potential for professional use include Facebook (Facebook, Inc, Menlo Park, California), Instagram (Facebook, Inc), YouTube (YouTube, LLC, San Bruno, California), and Periscope (Twitter, Inc). With Twitter and other social media options, now is the time for pathologists to increase our visibility on social media and worldwide.

- Our data demonstrate that residual thyroid FNA needle rinses are an adequate source of material for molecular diagnostic testing. Importantly, detection of a mutation implicated in thyroid malignancy was predictive of the final surgical diagnosis and clinical outcome. Our strategy to triage thyroid nodules with indeterminate cytology with molecular testing eliminates the need to perform additional FNA passes into dedicated media or to schedule additional invasive procedures. Further investigation with a larger sample size to confirm the clinical utility of our proposed strategy is underway.

Periscope is a live video-streaming smartphone application (app) that allows any individual with a smartphone to broadcast live video simultaneously to multiple smartphone users around the world. The aim of this review is to describe the potential of this emerging technology for global pathology education. To our knowledge, since the launch of the Periscope app (2015), only a handful of educational presentations by pathologists have been streamed as live video via Periscope. This review includes links to these initial attempts, a step-by-step guide for those interested in using the app for pathology education, and a summary of the pros and cons, including ethical/legal issues. We hope that pathologists will appreciate the potential of Periscope for sharing their knowledge, expertise, and research with a live (and potentially large) audience without the barriers associated with traditional video equipment and standard classroom/conference settings.

BACKGROUND:The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) provides a useful framework for the diagnosis of salivary gland fine-needle aspiration (FNA) biopsies. In this study, the MSRSGC was applied to salivary gland FNAs in pediatric patients to assess its usefulness and look at pitfalls. METHODS: The laboratory information system was queried over a 15-year period for all salivary gland FNAs in patients 18 years old or younger. Patient demographics, FNA diagnosis categorized according to the MSRSGC, and follow-up surgical pathology diagnoses were examined and correlated. RESULTS:Thirty-two cases were identified, with an average age of 12 years (range, 0.6-18 years). A majority of the cases (84.4%) were from the parotid region. Twenty of 32 cases (62.5%) had follow-up resection. MSRSGC recategorization diagnoses of the 32 FNA cases were 34% benign neoplasm, 31% nonneoplastic, 16% nondiagnostic, 9% atypia of undetermined significance, 3% salivary neoplasm of uncertain malignant potential, 3% suspicious for malignancy, and 3% malignant. Overall, the sensitivity and specificity were 100% and 80%, respectively. On follow-up resection, 55% were neoplastic: pleomorphic adenomas (n = 6; 55%), pilomatricoma (n = 3; 28%), mucoepidermoid carcinoma (n = 1; 9%), schwannoma (n = 1; 9%), and myofibroma (n = 1; 9%). CONCLUSIONS: The MSRSGC performed fairly well in the pediatric population with a low overall risk of malignancy (6%) and high sensitivity. Although the majority of pediatric salivary gland FNAs were benign, 55% of resected cases were positive for a neoplasm, with benign neoplasms outnumbering malignancy. Challenging entities included inflammatory conditions, like immunoglobulin G4-related sialadenitis, and skin and soft tissue lesions near the salivary gland.