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Background: Focal adhesion kinase (FAK) plays an important role in tumor metastasis. The purpose of this study was to evaluate the significance of FAK expression in surgically treated patients with hypopharyngeal cancer., Methods: We retrospectively reviewed the clinical charts of patients treated at our institution between 2004 and 2012 and identified 87 patients with hypopharyngeal cancer. FAK expression status was retrospectively evaluated using immunohistochemistry., Results: FAK-positive patients displayed significantly worse disease-specific survival than FAK-negative patients (p = .001). Multivariate analyses revealed that FAK positivity and extracapsular spread (ECS) were independent, significant adverse prognostic factors. Furthermore, FAK positivity significantly correlated with the number of metastatic lymph nodes (p = .048), and FAK-positive patients displayed a higher incidence of distant metastases (p = .009)., Conclusion: The current study demonstrated that upregulated FAK expression correlates with poor prognosis and tumor dissemination in surgically treated patients with hypopharyngeal cancer. © 2016 Wiley Periodicals, Inc. Head Neck 38:1164-1169, 2016., (© 2016 Wiley Periodicals, Inc.)

RECQL1 and WRN proteins are RecQ DNA helicases that participate in suppression of DNA hyper-recombination and repair. In this study, we report evidence supporting their candidacy as cancer therapeutic targets. In hypopharyngeal carcinomas, which have the worst prognosis among head and neck squamous cell carcinomas (HNSCC) that are rapidly rising in incidence, we found that RECQL1 and WRN proteins are highly expressed and that siRNA-mediated silencing of either gene suppressed carcinoma cell growth in vitro. Similarly, siRNA administration in a murine xenograft model of hypopharyngeal carcinoma markedly inhibited tumor growth. Moreover, combining either siRNA with cis-platinum (II) diammine dichloride significantly augmented the in vivo anticancer effects of this drug that is used commonly in HNSCC treatment. Notably, we observed no recurrence of some tumors following siRNA treatment in this model. Our findings offer a preclinical proof of concept for RECQL1 and WRN proteins as novel therapeutic targets to treat aggressive HNSCC and perhaps other cancers., (©2011 AACR.)

Background: The reactivation of the telomerase seems to be an important step in the carcinogenesis of most human cancer types. Cell clones, which express this enzyme, get the ability of indefinite proliferation, means become immortal., Methods: In this study, 80 patients with squamous cell carcinomas (SSC) in oral cavity, oropharynx, hypopharynx and larynx were recorded prospectively concerning a possible correlation of telomerase activity and clinical and prognostic factors. Telomerase activity was analysed by a modified telomeric repeat amplification protocol (TRAP) assay., Results: In 75% of the tumour tissues the telomerase was demonstrated independently of the localization of the tumour. The known clinical prognostic factors did not show any correlation to the expression rate of the telomerase activity in the tumour tissues. Also, reactivated telomerase did not affect the tumour-dependent survival. Only the number of lymph node metastases was in tendency higher in patients with telomerase-positive tumours. The number and timeframe of local and regional recurrences was not influenced by the telomerase status., Conclusions: Although telomerase seems to be an important part of the carcinogenesis of SCC our data show that the reactivation of telomerase in tumour tissue did not have any prognostic significance for these tumours. The tendency that tumours with active telomerase developed lymph node metastases in a higher number should be evaluated by further enlarged studies for its clinical relevance.

Objective: Association of glutathione-S-transferase M1 (GSTM1) polymorphisms and cancer has been demonstrated. Possible underlying mechanisms and genotype-phenotype correlations are not adequately investigated. The aim of this study was to investigate the influence of the GSTM1-null-genotype on the level of GSTM enzyme concentration and on the enzyme activity of GST in patients with head and neck cancer (HNC)., Methods: We investigated in 83 patients and 91 healthy controls the GSTM1 polymorphisms, GSTM1 protein concentration, GSTM1 protein in tumor tissues, and total GST enzyme activity., Results: Total GST enzyme activity was significantly lower in patients with HNC (208 +/- 9 micromol/min*l) than in controls (264 +/- 11 micromol/min*l, P< 0.0001) but did not depend on GSTM1-genotype (P = 0.1). GSTM protein concentration in null-genotype patients (3.6 +/- 2.5 microg/mL, mean +/- SE) was significantly lower than in GSTM1 allele carriers (26.7 +/- 9.6 microg/ml, P< 0.0001); GSTM protein expression did not depend on GSTM1-genotype (P> 0.5)., Conclusion: GST enzyme activity in patients with HNC is suppressed, indicating impaired detoxification capacity of tobacco-smoke-related carcinogens. This suppression is not correlated with the GSTM1-genotype.

Background: Serum liver function tests (LFTs) are used in the initial evaluation of patients with head and neck squamous cell carcinoma (SCC) to evaluate hepatic function and to screen for liver metastases., Methods: One hundred forty patients initially seen with SCC between 1988 and 1991 were followed for a minimum of 2 years to determine the significance of abnormal LFTs at presentation., Results: Abnormal values were found in 69 patients (49%), including elevated alkaline phosphatase in 37 (26%) and lactic dehydrogenase in 25 (18%). Abnormal values were most commonly attributed to alcohol-related liver disease. No liver metastases were identified at initial screening. LFTs were normal at presentation in all three patients subsequently identified with liver metastases during follow-up., Conclusions: Abnormal LFTs are commonly encountered but are of little value in identifying patients with liver metastases during initial assessment. Modest elevation of LFTs should not necessitate costly and time-consuming investigation to exclude hepatic metastasis.

Identification of prognostic factors in squamous cell head and neck cancers involves analysis of highly diverse clinical and biological parameters. This study analyzed the prognostic value of clinical variables (age, sex, tumor site, stage) and biologic parameters (squamous cell carcinoma antigen [SCC], serum thymidine kinase activity [TK], fibrin, sedimentation rate [SR]) at the time of diagnosis of squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx) in 189 patients. Among the clinical variables investigated, UICC stage III-IV disease (p < .0002), a hypopharyngeal site (p < .02), and age over 60 years (p < .01) were all associated with a poor prognosis. Similarly, analysis of biological blood variables allowed definition of cut-off values above which the prognosis was poor: SCC 2.5 ng/mL (p < .01), fibrin 3.5 g/L (p < .01), TK 7 IU/L (p < .0005), and SR 15 mm per first hour (p < .0000). Cox regression analysis of overall survival identified the UICC stage (p < .000), the SR (p < .001), and serum TK (p < .02) as the main independent prognostic factors. A separate study on a small number of head and neck cancer patients revealed higher TK levels in malignant squamous cell carcinoma tissue than in adjacent healthy tissue.