Association of human papillomavirus integration with better patient outcomes in oropharyngeal squamous cell carcinoma.

Background: The molecular drivers of human papillomavirus-related head and neck squamous cell carcinoma (HPV + HNSCC) are not entirely understood. This study evaluated the relationship between HPV integration, expression of E6/E7, and patient outcomes in p16+ HNSCCs.

Methods: HPV type was determined by HPV PCR-MassArray, and integration was called using detection of integrated papillomavirus sequences polymerase chain reaction (PCR).

Cancer Stem Cell Signaling during Repopulation in Head and Neck Cancer.

The aim of the study was to investigate cancer stem signaling during the repopulation response of a head and neck squamous cell cancer (HNSCC) xenograft after radiation treatment. Xenografts were generated from low passage HNSCC cells and were treated with either sham radiation or 15 Gy in one fraction. At different time points, days 0, 3, and 10 for controls and days 4, 7, 12, and 21, after irradiation, 3 tumors per group were harvested for global gene expression, pathway analysis, and immunohistochemical evaluation.

Crizotinib Fails to Enhance the Effect of Radiation in Head and Neck Squamous Cell Carcinoma Xenografts.

Aim: Mesenchymal-epithelial transition factor (MET), a receptor tyrosine kinase, is expressed in head and neck squamous cell carcinomas (HNSCC) and is involved in tumor progression and associated with poor prognosis. MET can be inhibited by crizotinib, a potent ATP-competitive kinase inhibitor. We examined the effects of combining crizotinib and radiation in a pre-clinical HNSCC model.

Gene Expression Characterization of HPV Positive Head and Neck Cancer to Predict Response to Chemoradiation.

Human papillomavirus (HPV) has been shown to have a causal role in the development of head and neck squamous cell carcinoma. While HPV-positive head and neck cancer is associated with a better response to treatment in the majority of patients, there is a subset who does not respond favorably to current therapy. Identification of these patients could prevent unnecessary morbidity and indicate the need for alternative therapeutic options.

The challenge of sustaining a hospital-based biobank and core molecular laboratory: the Beaumont experience.

The Beaumont Health System BioBank was established in 2008, not only to leverage the potential to collect biospecimens for translational research, but to undertake such research in a seamless facility that combined high quality biobanking with state-of-the-art laboratory platforms geared towards biospecimen-based research. This report describes the challenge of sustaining a hospital-based biobank with an operating budget exceeding $1,000,000 in a financial climate that favors short-term fiscal goals rather than long-term scientific ambitions. Some of the key areas that are discussed include grants, philanthropy, accreditation, process improvement and commercialization of samples and services.

Gene expression changes during repopulation in a head and neck cancer xenograft.

Background/purpose: To investigate temporal changes in global gene expression and pathways involved in the response to irradiation during phases of growth inhibition, recovery and repopulation in a human head and neck squamous cell cancer (HNSCC) xenograft.

Methods And Materials: Low passage head and neck squamous cancer cells (UT-14-SCC) were injected into the flanks of female nu/nu mice to generate xenografts. After tumors reached a size of 500 mm3, they were treated with either sham RT or 15Gy in one fraction.

Beaumont health system biobank: a multidisciplinary biorepository and translational research facility.

The Beaumont BioBank model is a multidisciplinary facility that is designed to provide access and opportunity for research-minded clinicians to become involved in research without the need for their own research infrastructure, thus increasing the research effort across the Health System. We describe a biobank model that works primarily in operating rooms for tissue collection and utilizes a generic consent process to facilitate rapid and accurate collection of biospecimens. The model combines both a biorepository that collects specimens based on clinical questions and also a translational research facility that undertakes biomarker-based research on those specimens in a seamless and efficient process.

Evaluation of genetic biomarkers for distinguishing benign from malignant thyroid neoplasms.

Background: Fine-needle aspiration (FNA) aids in the diagnosis of thyroid nodules. The expression of previously implicated genes was examined to potentially discriminate between benign and malignant thyroid samples.

Methods: Patients included for study had cytology demonstrating follicular cells of undetermined significance, atypical cells of undetermined significance, follicular neoplasm, or suspicion of malignancy with one of the following postoperative diagnoses: follicular thyroid adenomas, follicular thyroid carcinomas, or follicular variant of papillary thyroid carcinomas (FV-PTCs).

c-Met expression is a marker of poor prognosis in patients with locally advanced head and neck squamous cell carcinoma treated with chemoradiation.

Purpose: To examine the prognostic significance of c-Met expression in relation to p16 and epidermal growth factor receptor (EGFR) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with definitive concurrent chemoradiation.

Methods And Materials: Archival tissue from 107 HNSCC patients treated with chemoradiation was retrieved, and a tissue microarray was assembled. Immunohistochemical staining of c-Met, p16, and EGFR was performed.

A novel panel of biomarkers predicts radioresistance in patients with squamous cell carcinoma of the head and neck.

Purpose: Global gene expression analysis was performed on pre-treatment biopsies from patients with squamous cell carcinoma of the head and neck (SCCHN) to discover biomarkers that can predict outcome of radiation based therapy.

Methods: We initially evaluated RNA expression using cDNA microarray analysis of 38 patients that received radiotherapy (RT). The five strongest candidates (VEGF, BCL-2, CLAUDIN-4, YAP-1 and c-MET) were then analysed in pre-treatment biopsies in a second group of 86 patients who received radiation based treatment using immunohistochemical staining (IHC), prepared by tissue microarray.

Toxicities and costs of placing prophylactic and reactive percutaneous gastrostomy tubes in patients with locally advanced head and neck cancers treated with chemoradiotherapy.

Background: We compared dependence rates, complications, toxicities, and costs associated with prophylactic versus reactive percutaneous endoscopic gastrostomy (PEG) tube placement.

Methods: One hundred ninety-three patients with locally advanced head and neck squamous cell carcinoma treated with concurrent chemoradiotherapy were retrospectively reviewed.

Results: The 1-year and 2-year actuarial PEG tube dependence rate of the entire cohort was 24% and 13%, respectively.

A matched-pair comparison of intensity-modulated radiation therapy with cetuximab versus intensity-modulated radiation therapy with platinum-based chemotherapy for locally advanced head neck cancer.

Purpose: We retrospectively compared the efficacy of intensity-modulated radiotherapy (IMRT) and cetuximab (IMRT/cetuximab) versus IMRT and platinum-based chemotherapy (IMRT/platinum) for locally advanced head neck squamous cell carcinoma (LAHNSCC).

Methods: Thirty-one IMRT/cetuximab patients were matched 1:2 with 62 IMRT/platinum patients according to primary site and clinical stage. The primary endpoint was locoregional recurrence (LRR), and secondary endpoints included distant metastasis (DM), cause-specific survival (CSS), and overall survival (OS).

SPIN: Development of sample-specific protein integrity numbers as an index of biospecimen quality.

It is widely accepted that variable biorepository specimen handling conditions can significantly alter outcomes of clinical research studies, suggesting the need for a metric for sample analyte protein integrity. In line with the National Cancer Institute (NCI) Best Practices, it is vital that the integrity of specimens used for biomarker studies are of the highest standard to ensure validity of the data they generate and confidence in the application of new findings to clinical management. We describe the creation of a program to discover proteins in biorepository samples that can be utilized to assess the integrity of stored specimens for protein-based biomarker studies, similar to the universally accepted quality metric for RNA, the RNA Integrity Number, or RIN.

Isolation and genomic characterization of stem cells in head and neck cancer.

Background: This study investigated the use of 3 different established cell-sorting strategies to isolate and characterize stem cells from head and neck cancer cell lines.

Methods: Five low-passage cell lines were subjected to cell sorting based on Hoechst side population, Aldefluor, and CD44 expression. Isolated cell populations were studied for gene expression, radiosensitivity, and chemosensitivity to cisplatin and paclitaxel.

p53 mutation and cyclin D1 amplification correlate with cisplatin sensitivity in xenografted human squamous cell carcinomas from head and neck.

To investigate the response of tumour growth to cisplatin treatment, in relation to p53 mutation and cyclin D1 dysregulation on DNA and protein level, biopsies from seven xenografted human squamous cell carcinomas from the head and neck were analysed with immunohistochemistry for p53 expression and cyclin D1 expression. Polymerase chain reaction-singlestranded conformation polymorphism was used to determine p53 mutations. Fluorescence in situ hybridization was performed to analyse cyclin D1 amplification.

Genomic screening of head and neck cancer and its implications for therapy planning.

Despite great technical improvements in radiotherapy and surgery, survival for patients with squamous cell carcinoma of the head and neck (SCCHN) has still not improved significantly over the last decades. Management of SCCHN has mainly been based on the TNM staging and site over this time period, even though we know that there are individual differences independent of the TNM status. Individual patients with small tumors might have a poor outcome, and patients with large tumors may end up with a favorable prognosis, despite their respective TNM classification.

Gene profiling in squamous cell carcinoma of the head and neck.

Survival for patients with squamous cell carcinoma of the head and neck (SCCHN) is still poor, despite great technical improvements in radiotherapy and surgery. A possible explanation for this is the lack of individualization in treatment based on biological properties of the tumors, resulting in over- as well as under treatment. Management of SCCHN has mainly been based on TNM classification over the last decades.

Genetic and expression profiles of squamous cell carcinoma of the head and neck correlate with cisplatin sensitivity and resistance in cell lines and patients.

Purpose: The choice of treatment for squamous cell carcinoma of the head and neck (SCCHN) is still primarily based on the tumor-node-metastasis classification. However, it is reasonable to believe that biological profiles of SCCHN may be independently associated with response to therapy. The aim of the present study was to examine genetic changes and gene expression profiles that might correlate with sensitivity to cisplatin [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] in 10 SCCHN cell lines.

Overexpression of cyclin D1 correlates with sensitivity to cisplatin in squamous cell carcinoma cell lines of the head and neck.

Objective: Treatment strategies for squamous cell carcinoma of the head and neck (SCCHN) are based on the TNM classification. Biological markers that can predict the response to therapy have so far not been introduced. The objective of this study was to investigate cyclin D1 deregulation relative to sensitivity to cisplatin.

Amplification of the cyclin D1 gene is associated with tumour subsite, DNA non-diploidy and high S-phase fraction in squamous cell carcinoma of the head and neck.

Amplification of CCND1 (cyclin D1 gene) in squamous cell carcinoma of the head and neck (SCCHN) is correlated to poor prognosis. The purpose of this study was to investigate whether CCND1 amplification is related to different subsites and also to DNA ploidy status and S-phase fraction (SPF). Biopsies from 67 patients with SCCHN were analysed for CCND1 amplification by fluorescence in situ hybridisation (FISH) and for ploidy status and SPF by flow cytometry (FCM).

The gene ratios c-MYC:cyclin-dependent kinase (CDK)N2A and CCND1:CDKN2A correlate with poor prognosis in squamous cell carcinoma of the head and neck.

Purpose: Tumor-Node-Metastasis classification does not fully predict outcome of treatment and prognosis in patients with squamous cell carcinoma of the head and neck. Different biomarkers have been suggested to yield additional prognostic information, but no single marker has thus far been introduced in the clinic. The objective of the present study was to analyze the copy number of the frequently amplified oncogenes CCND1 and c-MYC in relation to the commonly deleted tumor suppressor gene cyclin-dependent kinase (CDK)N2A (p16) to enhance the clinical significance.

Karyotypic heterogeneity and clonal evolution in squamous cell carcinomas of the head and neck.

Head and neck squamous cell carcinomas (HNSCC) are often characterized by complex karyotypic changes, and a substantial proportion of the reported tumors have shown intratumor heterogeneity in the form of cytogenetically related (40%) or unrelated clones (20%). In order to study intratumor heterogeneity and to distinguish the temporal order of chromosome rearrangements in these tumors, two or more samples from different areas of the same tumor were separately examined in 19 HNSCC, yielding karyotypes from a total of 42 tumor samples. Intrasample heterogeneity was observed in 16 samples.

Chromosomal translocations involving 11q13 contribute to cyclin D1 overexpression in squamous cell carcinoma of the head and neck.

CCND1 amplification results in cyclin D1 overexpression. However, other unidentified genetic mechanisms contribute to enhanced gene expression. In the present study, 32 squamous cell carcinoma of the head and neck (SCCHN) were investigated regarding chromosomal abnormalities involving 11q13 by cytogenetic analysis, genomic CCND1 amplification by differential PCR and FISH, and cyclin D1 expression on the mRNA and protein level by differential RT-PCR and immunohistochemistry, respectively.