Prognostic significance of ALDH1A1-positive cancer stem cells in patients with locally advanced, metastasized head and neck squamous cell carcinoma.

PURPOSE: Aldehyde dehydrogenase 1 (ALDH1A1) has now been recognized as a cancer stem(-like) cells (CSCs) marker in various tumors including head and neck squamous cell carcinoma (HNSCC). The objective of this study was to examine the expression of ALDH1A1 in patients with locally advanced, metastasized HNSCC and to determine its prognostic value. METHODS: Human papillomavirus genotypes and expression of ALDH1A1, Twist1, and p16 were analyzed in specimens of 81 patients with primary HNSCC and 49 lymph node metastases. Patient clinicopathologic and follow-up data were analyzed. RESULTS: Expression of ALDH1A1 was observed in 38 (46.9 %) of 81 primary tumors and 26 (53 %) of 49 lymph node metastases, respectively. Notably, the expression of ALDH1A1 was correlated significantly with poor tumor differentiation grade (p = 0.011). Interestingly, ALDH1A1 was observed co-expressed with Twist1 in primary tumor and lymph node metastases. Multivariate analysis showed that ALDH1A1 expression predicted poor prognosis in patients with HNSCC (p = 0.011) and the subgroup of oropharyngeal squamous cell carcinoma (p = 0.001). In the patient cohort with advanced, metastasized tumors, ALDH1A1 was identified as independent predictor of overall survival in both groups. CONCLUSIONS: Our results provide evidence for the prognostic value of ALDH1A1 as a CSC marker in patients with locally advanced, metastasized HNSCC.

Cochlear implant fixation: are sutures really necessary?

The objective of this study was to evaluate retrospectively the risk of cochlear implant migration and complications related to the here presented alternative surgical fixation technique of the receiver/stimulator without any foreign body materials. Fixation of the implant was achieved by an "L-shaped" muscle-periosteal flap and an exactly shaped bony well. Between January 2006 and December 2009, 247 consecutive primary cochlear implantations have been performed with the described technique in the Department of Otorhinolaryngology, Head and Neck surgery of the University of Cologne (tertiary referral center). Devices from different manufacturers have been implanted. Implantation age ranged from 6 months to 78 years (mean age: 24.50 years). Follow-up time ranged from 12 to 60 months. Neither implant dislocations nor migrations were observed in our patients. In four very young children (1.6 %), additional suture fixation of the implant was performed. Postoperative complications, i.e. seroma or hematoma were observed in a total of six cases (2.4 %). The here presented surgical fixation technique is a sufficient and reliable way for fixation of cochlear implants independent of the device type.

Clonal expansion of different mtDNA variants without selective advantage in solid tumors.

In search of tumor-specific mitochondrial DNA (mtDNA) mutations in head and neck squamous cell cancer, we found heteroplasmy in the blood of two individuals, i.e., these individuals carried two alleles of mtDNA. In both cases, the tumor was found to be homoplasmic, i.e., it contained only one of the two mtDNA alleles present in blood. More interestingly, in one case the tumor had acquired the wild-type allele, while in the other case it contained the mutant allele only. Sequencing of the whole 16.5 kb mtDNA showed that the observed heteroplasmic positions in the D-loop region, nucleotides 152 and 16187, respectively, were the only differences between tumor and blood mtDNA genotypes in these individuals. Our findings thus strongly support the hypothesis that accumulation of mtDNA mutations in solid tumors occurs by clonal and random expansion of pre-existing alleles and is not necessary for the metabolic changes generally associated with tumor formation, the Warburg effect.