Cancer

Abstract

CONTEXT:

-TTF-1 and napsin A immunomarkers have a crucial role in differentiating lung adenocarcinoma from lung squamous cell carcinoma and in identifying a primary lung adenocarcinoma when working on a tumor of unknown origin.

OBJECTIVES:

-To investigate the diagnostic sensitivity of ribonucleic acid in situ hybridization (RNAscope) in the detection of expression of these biomarkers in lung adenocarcinomas and to compare RNAscope to immunohistochemical techniques.

DESIGN:

Extranodal natural killer (NK)/T-cell lymphoma (ENKTL), nasal type, comprises NK or cytotoxic T cells. We evaluated the clinical impact of cell type and the usefulness of T-cell receptor (TCR) gene transcripts in distinguishing cell lineage. One hundred and eight cases of ENKTL were analyzed for TCR gene rearrangements using the BIOMED-2 protocol and for TCR gene expression using immunohistochemistry for TCR-βF1 and TCR-cγM1, and RNA in situ hybridization for TCR gene transcripts. Prognostic factors were analyzed.

Aberrant Notch signalling has been linked to many cancers including choroid plexus (CP) tumours, a group of rare and predominantly paediatric brain neoplasms. We developed animal models of CP tumours, by inducing sustained expression of Notch1, that recapitulate properties of human CP tumours with aberrant NOTCH signalling. Whole-transcriptome and functional analyses showed that tumour cell proliferation is associated with Sonic Hedgehog (Shh) in the tumour microenvironment.

Constitutive Wnt signaling promotes intestinal cell proliferation but signals from the tumor microenvironment are also required to support cancer development. The role that signaling proteins play to establish a tumor microenvironment has not been extensively studied. Therefore, we assessed the role of the pro-inflammatory Ikk-related kinase Ikkε in Wnt-driven tumor development. We found that Ikkε was activated in intestinal tumors forming upon loss of the tumor suppressor Apc.

Papillomaviruses (PV) are associated with benign mucosal and cutaneous epithelial proliferations. In dogs, PV-associated pigmented plaques and papillomas can undergo malignant transformation, but this is rare, and most cases of canine squamous cell carcinoma do not arise from PV-induced precursor lesions. We describe herein the progression of pigmented plaques to invasive and metastatic squamous cell carcinoma associated with 2 canine papillomaviruses (CPV) in 2 related Basenji dogs.

BACKGROUND

Subtyping non-small cell lung carcinomas (NSCLC) into adenocarcinoma (ACA) or squamous cell carcinoma (SQCC) is important for treatment and specimen triage for molecular studies. To preserve tissue for molecular studies in cytology/small biopsy specimens, a 2-antibody cocktail for NSCLC subtyping was developed.

METHODS

Objectives

Evaluation of human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) has become increasingly important for prognostication and clinical trial enrollment. This assessment is confounded in OPSCCs that are p16 positive by immunohistochemistry (IHC) but HPV negative by DNA in situ hybridization (DISH). This study evaluates whether E6/E7 mRNA in situ hybridization (RISH) can detect transcriptionally active HPV in these problematic cases.

Materials and methods

A key step of Wnt signaling activation is the recruitment of β-catenin to the Wnt target-gene promoter in the nucleus, but its mechanisms are largely unknown. Here, we identified FoxM1 as a novel target of Wnt signaling, which is essential for β-catenin/TCF4 transactivation. GSK3 phosphorylates FoxM1 on serine 474 which induces FoxM1 ubiquitination mediated by FBXW7. Wnt signaling activation inhibits FoxM1 phosphorylation by GSK3-Axin complex and leads to interaction between FoxM1 and deubiquitinating enzyme USP5, thereby deubiquitination and stabilization of FoxM1.

Abstract

BACKGROUND:

The incidence of p16 overexpression and the role of human papillomavirus (HPV) in cutaneous head and neck squamous cell carcinoma (cHNSCC) are unclear.

METHODS:

One hundred forty-three patients with cHNSCC lymph node metastases involving the parotid gland were evaluated for p16 expression by immunohistochemistry. The detection of 18 high-risk HPV subtypes was performed with HPV RNA in situ hybridization for a subset of 59 patients. The results were correlated with clinicopathological features and outcomes.

RESULTS:

APOBEC3B belongs to a protein family of cytidine deaminases that can insert mutations in DNA and RNA as a result of their ability to deaminate cytidine to uridine. It has been shown that APOBEC3B-catalysed deamination provides a chronic source of DNA damage in breast cancers. We investigated APOBEC3B expression in four drug resistant breast cancer cell lines (Doxorubicin, Etoposide, Paclitaxel and Docetaxel resistant MCF-7 cell lines) using a novel RNA in situ hybridization technology (RNAscope) and compared expression levels with drug sensitive MCF-7 cell line.