The objectivity illusion and voter polarization in the 2016 presidential election.

Two studies conducted during the 2016 presidential campaign examined the dynamics of the objectivity illusion, the belief that the views of "my side" are objective while the views of the opposing side are the product of bias. In the first, a three-stage longitudinal study spanning the presidential debates, supporters of the two candidates exhibited a large and generally symmetrical tendency to rate supporters of the candidate they personally favored as more influenced by appropriate (i.e., "normative") considerations, and less influenced by various sources of bias than supporters of the opposing candidate. This study broke new ground by demonstrating that the degree to which partisans displayed the objectivity illusion predicted subsequent bias in their perception of debate performance and polarization in their political attitudes over time, as well as closed-mindedness and antipathy toward political adversaries. These associations, furthermore, remained significant even after controlling for baseline levels of partisanship. A second study conducted 2 d before the election showed similar perceptions of objectivity versus bias in ratings of blog authors favoring the candidate participants personally supported or opposed. These ratings were again associated with polarization and, additionally, with the willingness to characterize supporters of the opposing candidate as evil and likely to commit acts of terrorism. At a time of particular political division and distrust in America, these findings point to the exacerbating role played by the illusion of objectivity.

Long Non-coding RNAs in Pulmonary Neuroendocrine Neoplasms.

Pulmonary neuroendocrine neoplasms (NENs) are classified into low-grade neuroendocrine tumors and high-grade neuroendocrine carcinomas (NECs). There are significant differences in therapeutic strategies of the different NEN subtypes, and therefore, precise classification of pulmonary NENs is critical. However, challenges in pulmonary NEN classification include overlap of diagnostic histological features among the subtypes and reduced or negative expression of neuroendocrine markers in poorly differentiated pulmonary NECs. Recently, transcription factor insulinoma-associated protein 1 (INSM1) was identified as a sensitive marker of neuroendocrine and neuroepithelial differentiation. In this study, INSM1 expression was detected by immunohistochemistry in greater than 94% of pulmonary NENs, indicating that it is a highly sensitive marker of pulmonary NENs and is useful to detect poorly differentiated pulmonary NECs. Although there are well-established morphological and immunohistologic criteria to diagnose pulmonary NENs, there is no universal consensus regarding prognostic markers of pulmonary NENs. Studies have shown that non-small cell lung cancers express long non-coding RNAs (lncRNAs), which regulate gene expression, epithelial-to-mesenchymal transition, and carcinogenesis. We characterized expression and function of lncRNAs, including HOX transcript antisense RNA (HOTAIR), maternally expressed 3 (MEG3), and prostate cancer antigen 3 (PCA3) in pulmonary NENs, including typical carcinoid tumors, atypical carcinoid tumors, small cell lung carcinoma (SCLC/NEC), and large cell neuroendocrine carcinoma (LCNEC/NEC). In situ hybridization and real-time polymerase chain reaction studies showed higher expression (p < 0.01) of all lncRNAs in SCLC/NEC. Small interfering RNA studies indicated a role for MEG3 and PCA3 in tumor proliferation. Therefore, these lncRNAs may serve as prognostic indicators of pulmonary NEN aggressiveness and as possible therapeutic targets.

A Comparison of E6H4 and G175-405 p16-specific Monoclonal Antibodies in Oropharyngeal Squamous Cell Carcinoma.

The purpose of this investigation is to directly compare G175-405 and E6H4 p16-specific antibodies as immunomarkers of HPV-driven oropharyngeal carcinoma. The investigators designed a retrospective analysis using specimens from an archived tissue bank with known in situ hybridization and polymerase chain reaction status for HPV DNA. Fifty randomly selected oropharyngeal specimens were evaluated with both the G175-405 and E6H4 p16-specific monoclonal antibodies. Two pathologists, blinded to the HPV-specific testing status, evaluated p16 positivity for both antibody clones. Interrater agreement was determined using a Cohen κ coefficient. Sensitivity and specificity values were calculated using a standard 2×2 contingency table, then compared using McNemar test. Interrater agreement for interpretation of p16 expression was 92% (κ=0.84) for the G175-405 clone and 100% for the E6H4 clone (κ=1.0). The G175-405 stain had a sensitivity of 0.917 and specificity of 0.846. The E6H4 stain had a sensitivity of 1.000 and specificity of 0.769. Using McNemar test, there were no significant differences found for sensitivity (P=0.480) or specificity (P=0.480) values. The results of this study suggest that though both G175-405 and E6H4 antibody stains are statistically comparable immunomarkers for HPV-driven oropharyngeal carcinoma, the E6H4 clone offers improved interobserver reliability.

Expression of Insulinoma-Associated Protein 1 (INSM1) and Orthopedia Homeobox (OTP) in Tumors with Neuroendocrine Differentiation at Rare Sites.

Insulinoma-associated protein 1 (INSM1) and orthopedia homeobox (OTP) are transcription factors that play a critical role in neuroendocrine (NE) and neuroepithelial cell development. INSM1 has been identified in multiple tumors of NE or neuroepithelial origin, whereas OTP expression has been mainly studied in NE tumors of pulmonary origin. Expression of OTP appears to correlate with poorer prognosis in pulmonary carcinoids; however, its expression patterns in other NE/neuroepithelial tumors need further investigation. Here, we assessed the diagnostic utility of INSM1 and OTP in tumors with NE differentiation at relatively uncommon sites including prostate, breast, and tumors of gynecologic origin. Thirty-two formalin-fixed, paraffin-embedded cases were used to construct a tissue microarray. Immunohistochemistry for INSM1 and OTP was performed and scored semi-quantitatively. INSM1 was diffusely expressed in 60% of gynecologic tumors, 71.4% of mammary carcinoma, and 25% of prostate adenocarcinoma with NE differentiation. Diffuse expression of OTP was detected in 50% of prostate adenocarcinoma with NE differentiation and 100% neuroendocrine carcinoma of the ovary. Immunostain for achaete-scute homolog 1, chromogranin, synaptophysin, and CD56 supported the NE and/or neuroepithelial differentiation of the tumors. In summary, INSM1 is expressed in most of the tumors with NE and neuroepithelial differentiation in this study, confirming the diagnostic utility of INSM1 as a novel and sensitive marker of NE/neuroepithelial differentiation. The expression of OTP in some NE tumors outside of lung expands the spectrum of tumors that may express this biomarker and should be considered when working up a NE tumor of unknown primary site.

p16 Immunohistochemistry Is a Useful Diagnostic Adjunct in Cases of Metastatic Cervical Carcinoma of Unknown Origin.

PURPOSE: Metastatic cervical carcinoma of unknown primary (MCCUP) is increasing in frequency owing in part to rising human papillomavirus (HPV)-driven oropharyngeal carcinoma. Identifying the primary site is valuable, because it is associated with increased survival and decreased morbidity. HPV-positive cervical nodal disease focuses attention on the oropharynx for directed biopsy examinations, including tonsillectomy. When the primary is small, carcinoma might not be apparent by traditional hematoxylin and eosin (H&E) staining alone. MATERIALS AND METHODS: This report describes 2 cases of p16-positive MCCUP in which a small primary carcinoma was not readily identified in surgical specimens using H&E staining. RESULTS: Additional evaluation of the specimens with p16 immunohistochemistry (IHC) showed carcinoma in these 2 cases. CONCLUSIONS: When H&E staining does not show carcinoma in cases of MCCUP, p16 IHC should be considered given the high prevalence of HPV-positive MCCUP and the potential for identification of a small primary tumor that might otherwise be missed with H&E staining.

Pathologic Features of Esophageal and Gastric Malignancies.

Esophageal and gastric carcinomas affect millions of individuals worldwide, placing a considerable burden on society. Unfortunately, preventative medicine falls short as screening methods for the upper gastrointestinal tract lack the ability to detect early onset disease. The overwhelming majority of cases present after symptoms appear when individuals have advanced disease with a poor prognosis. Further complicating matters, the anatomic location of these neoplasms engenders rapid tumor progression, which repeatedly thwarts successful surgical treatment. This chapter will focus on the pathological features of malignant neoplasms of the esophagus and stomach.

Pathologic Features of Miscellaneous Foregut Malignancies.

In addition to tumors arising from the primary mucosal epithelium, the foregut is host to a variety of non-epithelial precursor cells which may give rise to neoplasms of neuroendocrine, mesenchymal, and hematolymphoid lineages. Many of these lesions also occur outside of the gastrointestinal tract, such as the extranodal lymphomas and many of the sarcomas, and in many cases share the features of their non-alimentary counterparts. This heterogeneous collection of malignancies features a wide spectrum of clinical presentations, morphologic and histopathologic features, genetic underpinnings, and treatment considerations. Although encountered less frequently than primary carcinomas, it is important to correctly recognize and classify these lesions to effectively manage and prognosticate the patients in which they occur. In this chapter, we focus on the clinical, morphologic, and genetic features of the primary esophageal and gastric neoplasms of neuroendocrine, mesenchymal, and lymphoid origin.