Label-Free Semiquantitative Liquid Chromatography-Tandem Mass Spectrometry Proteomics Analysis of Laryngeal/Hypopharyngeal Squamous Cell Carcinoma on Formalin-Fixed, Paraffin-Embedded Tissue Samples - a Pilot Study.

Squamous cell carcinoma (SCC) of the head and neck region is the sixth most frequent malignancy with high mortality rate. Due to its poor prognosis it is considered a growing public health problem worldwide inspite of existing treatment modalities. Thus, early diagnosis of new diseases and recurrences is emerging on one hand, but on the other hand troublesome in the lack of reliable tumor markers in this field. The rapid development of proteomics has opened new perspectives in tumor marker discovery. Liquid chromatography/mass spectrometry (LC/MS) as the gold standard in proteomics enables the semi-quantitative analysis of proteins within various tissues. Abundance differences between tumor and normal tissue also can be interpreted as tumor specific changes. The aim of this study was to identify potential tumor markers of laryngeal/hypopharyngeal SCC by revealing abundance changes between cancerous and the surrounding phenotypically healthy tissue. After separating the phenotypically cancerous and healthy parts of formalin-fixed paraffin-embedded tissues, each sample underwent protein recovery process and tryptic digestion for label-free semi-quantitative LC/MS analysis. Eight proteins showed significantly higher abundance in tumor including tenascin, transmembrane emp24 domain-containing protein 2, cytoplasmic dynein light chain 1, coactosin-like protein, small proline-rich protein 2D, nucleolin, U5 small nuclear RNP 200-kDa helicase and fatty aldehyde dehydrogenase. Desmoglein-1 and keratin type I cytoskeletal 9 were down-regulated in tumor. Using Ingenuity Pathway Analysis we mapped the signaling pathways these proteins play role in regarding other tumors. Based on these findings these proteins may serve as promising biomarkers in the fight against laryngeal/hypopharyngeal SCCs.

Author Correction: Visualization of mucosal field in HPV positive and negative oropharyngeal squamous cell carcinomas: combined genomic and radiology based 3D model.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Visualization of mucosal field in HPV positive and negative oropharyngeal squamous cell carcinomas: combined genomic and radiology based 3D model.

The aim of this study was to visualize the tumor propagation and surrounding mucosal field in radiography-based 3D model for advanced stage HNSCC and combine it with HPV genotyping and miRNA expression characterization of the visualized area. 25 patients with T1-3 clinical stage HNSCC were enrolled in mapping biopsy sampling. Biopsy samples were evaluated for HPV positivity and miR-21-5p, miR-143, miR-155, miR-221-5p expression in Digital Droplet PCR system. Significant miRNA expression differences of HPV positive tumor tissue biopsies were found for miR-21-5p, miR-143 and miR-221-5p compared to the HPV negative tumor biopsy series. Peritumoral mucosa showed patchy pattern alterations of miR-21-5p and miR-155 in HPV positive cases, while gradual change of miR-21-5p and miR-221-5p was seen in HPV negative tumors. In our study we found differences of the miRNA expression patterns among the HPV positive and negative tumorous tissues as well as the surrounding mucosal fields. The CT based 3D models of the cancer field and surrounding mucosal surface can be utilized to improve proper preoperative planning. Complex evaluation of HNSCC tissue organization field can elucidate the clinical and molecular differentiation of HPV positive and negative cases, and enhance effective organ saving therapeutic strategies.

[First report on successful application of nivolumab in Hungary for the treatment of locally recurrent head and neck squamous cell carcinoma]. / Immunterápia elsõ hatékony alkalmazása Magyarországon lokálisan kiújult fej-nyaki laphámkarcinómás betegnél.

The prognosis for recurrent/metastatic head and neck squamous cell cancer (R/M HNSCC) remains dismal and its treatment poses a challenge for oncologists. Nivolumab belongs to the class of immune checkpoint inhibitors (ICI) and is an antibody developed to target the programmed cell death protein 1 (PD-1) receptor. The CheckMate 141 randomized phase 3 trial proved the efficacy of nivolumab in the treatment of R/M HNSCC as it was shown to significantly increase overall survival and quality of life. We present the case of a 53-year-old woman with R/M HNSCC who was given nivolumab monotherapy, as third-line treatment due the progression of her tumor. After treatment with nivolumab, the size of her tumor decreased, then was stable, while she did not experience any adverse events or notable side effects. Our case report is the first to demonstrate the application of nivolumab in R/M HNSCC in Hungary.

Comparative miRNA Expression Profile Analysis of Squamous Cell Carcinoma and Peritumoral Mucosa from the Meso- and Hypopharynx.

BACKGROUND/AIM: The role of microRNAs (miRNA) in carcinogenesis is related to their genome-regulatory function. The aim of the present study was to identify and compare miRNA expression signatures of meso- and hypopharynx squamous cell cancers in consideration of the cancer field hypothesis. PATIENTS AND METHODS: Thirteen snap-frozen biopsy series of tumors and peritumoral tissues from the meso- and hypopharynx were analyzed regarding their miRNA expression with quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Significant miRNA expression changes of miR-21, -27a, -34a, -143 and -146a were found in peritumoral tissues that were dependent from the tumor location and the distance from the primary tumor site. CONCLUSION: miRNA expression analysis was found to be appropriate for molecular segregation of tumor location and peritumoral tissue segments, and appears to be a promising marker for cancer field characterization.

[MicroRNA expression profiles in squamous cell carcinomas of the meso- and hypopharynx]. / Mikro-RNS-expressziós mintázatok mesopharynx-hypopharynx laphámcarcinomákban.

INTRODUCTION: MicroRNAs play a role in carcinogenesis through their genome regulatory function. AIM: The aim of the authors was to identify and compare microRNA expression signatures of meso- and hypopharynx squamous cell cancers on the basis of the cancer field hypothesis. METHOD: Using standard mapping biopsy (tumour tissue and macroscopically normal tissues obtained 1, 2 and 3 cm from margin) 13 snap frozen sample series were analysed for microRNA expression with quantitative real-time polymerase chain reaction. RESULTS: MiR-221 was significantly overexpressed in mesopharynx cancers, whole miR-21, miR-143 and miR-155 showed significant overexpression in hypopharynx cancers. CONCLUSIONS: Using microRNA expression profiles the authors were able to distinguish peritumoural tissues according to distance from the primary tumour site. Future application of the method may prove to be useful in early detection of the altered epigenetic regulation in tissue fields representing normal phenotype. This may be helpful in cancer risk assessment and prevention.

Health expenditure trends in OECD countries, 1990-2001.

This article presents data on health care spending for 30 OECD countries from OECD Health Data 2003, the latest edition of OECD's annual data collection on health systems across industrialized countries. OECD data show health care expenditures as a proportion of gross domestic product at an all-time high, due to both increased expenditures and overall economic slow-down. The article discusses similarities and differences across countries in how health care expenditures are funded and how the health care dollar is spent among types of services.