Georg Haymerle

Impact of Sonic Hedgehog Pathway Expression on Outcome in HPV Negative Head and Neck Carcinoma Patients after Surgery and Adjuvant Radiotherapy.

Introduction HPV positive patients suffering from head and neck cancer benefit from intensified radiotherapy when applied as a primary as well as an adjuvant treatment strategy. However, HPV negative patients treated with surgery and adjuvant radiotherapy lack validated prognostic biomarkers. It is therefore important to define prognostic biomarkers in this particular patient population. Especially, ´high-risk groups´ need to be defined in order to adapt treatment protocols. Since dysregulation of the sonic hedgehog pathway plays an important role in carcinogenesis, we aimed to assess whether members of the sonic hedgehog-signaling pathway may act as prognostic factors in patients with HPV negative head and neck squamous cell carcinoma. Materials and Methods In this prospective study, pretreatment tumor biopsies of patients with head and neck squamous cell carcinoma were taken during panendoscopy (2005 to 2008). All patients were treated with surgery and postoperative radiotherapy. After assessment of HPV and p16 status, protein expression profiles of the Sonic hedgehog-signaling pathway were determined by immunohistochemistry and tissue microarray analyses in 36 HPV negative tumor biopsies. Expression profiles of Sonic hedgehog, Indian hedgehog, Patched, Smoothened, Gli-1, Gli-2 and Gli-3 were correlated with patients´ clinical data, local-control rate, disease-free as well as overall survival. Data from The Cancer Genome Atlas databank were used for external validation of our results. Results Gli-1 (p = 0.04) and Gli-2 (p = 0.02) overexpression was significantly linked to improved overall survival of HPV negative patients. Gli-2 (p = 0.04) overexpression correlated significantly with prolonged disease-free survival. Cox-multivariate analysis showed that overexpression of Gli-2 correlated independently (HR 0.40, 95% CI 0.16–0.95, p = 0.03) with increased overall survival. Discussion Gli-1 and Gli-2 overexpression represents a substantial prognostic factor for overall and disease-free survival in patients with locally advanced HPV negative head and neck cancer undergoing surgery and postoperative radiotherapy.

Merkel cell carcinoma: Overall survival after open biopsy versus wide local excision

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin with a dismal prognosis.

Expression of Merkelcell polyomavirus (MCPyV) large T-antigen in Merkel cell carcinoma lymph node metastases predicts poor outcome

Background The aim of this study was to determine the prevalence of MCPyV in Merkel cell carcinoma (MCC) primaries versus lymph node metastasis and to evaluate possible prognostic factors. Methods Samples of MCC primaries and lymph node metastases were stained immunohistochemically for the MCPyV large T-antigen and expression was compared to patients´ clinical outcome. Results 41 MCC patients were included. 33 (61%) out of 54 specimens were MCPyV-positive in the immunohistochemistry. 15 (47%) out of 32 primary tumors were positive compared to 18 (82%) out of 22 lymph node metastases. Eleven patients with positive polyomavirus expression died from the carcinoma compared to 4 patients without virus expression. Cox regression analysis showed worse disease-free survival in patients with MCPyV compared to virus-negative lymph nodes (p = 0.002). Conclusions To our knowledge this is the first study to describe a negative prognostic effect of the MCPyV expression in lymph node metastasis in MCC patients.

ELMO3 predicts poor outcome in T1 laryngeal cancer

Despite the excellent overall survival of 92%‐97% in early glottic cancer, recurrence rates of 13%‐20% have not improved in the last decades. The engulfment and cell motility protein 3 (ELMO3) have been described as prognostic marker in patients with lung cancer. The aim of this study was to investigate the expression of ELMO3 in early laryngeal cancer patients treated with TLM and to evaluate its prognostic significance on clinical outcome.

Expression of 15-lipoxygenase-1 in Merkel cell carcinoma is linked to advanced disease

The purpose of this study was to determine whether the expression of 15‐lipoxygenase‐1 (ALOX15) in primary tumour specimens predicts lymph node metastasis and subsequently clinical outcome in Merkel cell carcinoma (MCC) patients.

Incurable, progressive Merkel cell carcinoma: A single-institution study of 54 cases

M. Bowler S. Monks C. English M. Sadadcharam R. Perkins N. Bateman I.A. Bruce D. Atkinson B. McGrath Paediatric Anaesthesia, Royal Manchester Children’s Hospital, Manchester, UK Anaesthesia, East Lancashire Hospitals NHS Trust, Blackburn, UK Paediatric Otorhinolaryngology, Royal Manchester Children’s Hospital, Manchester, UK Paediatric Otolaryngology MAHSC, University of Manchester, Manchester, UK Anaesthesia & Intensive Care Medicine, Manchester Royal Infirmiry, Central Manchester Foundation Trust, Manchester, UK Anaesthesia & Intensive Care Medicine, University Hospital South Manchester, Manchester, UK University of Manchester, Manchester, UK NHS England, Manchester, UK

The effect of adjuvant radiotherapy on radial forearm free flap volume after soft palate reconstruction in 13 patients

Dear Editor, Treatment options for squamous cell carcinoma of the soft palate include surgical resection followed by radiotherapy or primary radiotherapy. In most cases, sufficient resection margins require reconstruction of the defect with free flaps. The most common flaps used in oropharyngeal carcinoma are the radial forearm free flap and the anterolateral thigh and latissimus dorsi free flap. According to the magnitude of the resection defect, surgeons estimate the size and volume of soft tissue transfer needed for an optimal aesthetic and in particular functional outcome. This, however, depicts a great challenge as a high variability in the extent of volume loss in free flaps has been described in previous studies. In particular, flap volume loss ranged between 10% and 39% after reconstruction of oropharyngeal defects. The speech and swallowing outcome are influenced by various factors including tumour size, patient age, prior treatment neck dissection and comorbidities such as diabetes mellitus, cerebrovascular disease and hypertension. Current literature emphasises a general overcorrection for oropharyngeal reconstruction regardless of postoperative irradiation. The aim of our present study, therefore, was to evaluate the effect of radiation therapy on the volume shrinkage after reconstruction of the soft palate with radial forearm free flap.