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Overall survival of head and neck squamous cell carcinoma patients on the whole has not dramatically improved in the last 30 years. One of the reasons is that tumour, node, metastasis classification is probably in some cases inadequate, since similar cases under a clinico-pathological point of view, may differ widely in prognosis. The most important reason for this is probably the extreme biological heterogeneity, which leads to a lack of consistency in treatment planning. The aim of the present review is to delineate the advances and the perspectives of clinical use of molecular characterization, which is an attempt to break through such molecular heterogeneity and to define, together with tumour, node, metastasis classification, homogeneous groups of patients for prognostic stratification and treatment selection.

The purpose of this review is to summarize the recent understanding of the harmful effects of gastric and duodenal agents on mucosa of the upper aerodigestive tract in patients with duodeno-gastro-esophageal reflux.

The authors evaluated serum levels of folate, homocysteine, and vitamin B12 in patients with head and neck squamous cell carcinoma (HNSCC) and in patients with laryngeal leukoplakia, a well known preneoplastic lesion.One hundred forty‐four consecutive, untreated patients with HNSCC and 40 consecutive, untreated patients with laryngeal leukoplakia were enrolled in the Department of Otolaryngology at the authors' institution. Data from those patients were compared with data from one control group, which included 90 smokers, and from another control group, which included 120 nonsmokers. Serum levels of homocysteine, folate, and vitamin B12 were measured by an automated immunoassay method based on fluorescence polarization immunoassay technology.Comparing groups by Student–Newman–Keuls test, serum folate levels were significantly lower in patients with HNSCC and in patients with laryngeal leukoplakia compared with serum folate levels in both the smoker control group and the nonsmoker control group. Serum homocysteine levels in patients with HNSCC were significantly higher compared with homocysteine levels both in the smoker and nonsmoker control groups and in patients with laryngeal leukoplakia. There were no statistically significant differences between groups in serum vitamin B12 levels.A role for folate deficiency as a risk factor in head and neck carcinogenesis is plausible. A chemoprevention protocol with folate is both feasible and ethically correct and is in progress at the authors' institution. Homocysteine levels in patients with HNSCC probably are affected largely by the HNSCC phenotype. An accumulation of homocysteine may reveal a genetic defect, which, theoretically, may be a target for pharmacologic therapy, for example, with antifolic drugs. Cancer 2005. © 2004 American Cancer Society.

Epidermal growth factor receptor (EGFR) overexpression is an unfavorable prognostic marker in laryngeal squamous cell carcinoma (SCC). EGFR stimulates cyclooxygenase-2 (COX-2) expression in normal human keratinocytes and squamous carcinoma cells. Based on these observations a prognostic role of COX-2 expression in laryngeal SCC can be hypothesized. Consequently, COX-2 expression was studied in laryngeal SCC (median follow-up = 47 months; range: 2–87 months) by quantitative immunohistochemistry (n = 61) and EGFR by binding assay (n = 51). Well-differentiated regions of laryngeal SCC revealed strong COX-2 immunostaining, whereas histologically normal areas neighboring tumor as well as poorly-differentiated tumors were negative. Immunohistochemical results were confirmed by Western blot analyses. Cox's regression analysis showed that the combination of low levels of COX-2 integrated density and high levels of EGFR covariates provided strong prediction, at 5-year follow-up, of both poor overall survival (χ² = 12.905; p = 0.0016) and relapse-free survival (χ² = 9.209; p = 0.01). In vitro studies on CO-K3 cell line, obtained from an EGFR positive, COX-2 negative poorly-differentiated laryngeal SCC, revealed that EGF stimulation failed to induce COX-2 expression and PGE2 production suggesting a change in EGFR signaling pathway. These findings indicate that COX-2 is overexpressed in less aggressive, low grade laryngeal SCC, whereas its expression is lost when tumors progress to a more malignant phenotype. © 2001 Wiley-Liss, Inc.

Specimens of laryngeal squamous cell carcinoma (LSCC) were examined for epidermal growth factor receptor (EGFR) content using a radioreceptor method; 140 untreated consecutive patients with primary LSCC undergoing initial surgical resection were followed up for a median of 49 months (range 2–84 months) after surgery. Cox univariate regression analysis using EGFR as a continuous variable showed that EGFR levels were directly associated with the risk of lymph node metastasis. A significant relationship between EGFR status and cervical node metastasis was observed. The cutoff value of 20 fmol/mg protein was the best prognostic discriminator. The 5-year metastasis-free survival (MFS) was 66% for patients with EGFR⁻ tumors compared with 15% for patients with EGFR⁺ tumors. By multivariate analysis, the EGFR status appeared to be a significant independent prognostic factor for MFS. Our results suggest that the assessment of EGFR status at the time of diagnosis may identify a subset of LSCC patients highly susceptible to neck node metastases thus defining therapy accordingly. Int. J. Cancer (Pred. Oncol.) 84:188–191, 1999. © 1999 Wiley-Liss, Inc.

Quercetin and tamoxifen, in a range of concentrations between 0.01 and 5 μM, exert a dose-dependent inhibition on the anchorage-dependent and anchorage-independent cell growth of Hep2 and CO-K3 laryngeal cancer cell lines. Cell cycle analysis revealed that the growth-inhibitory effect was associated with a block of the cells at the G2/M checkpoint of the cell cycle followed by DNA fragmentation. This suggests that the failure of cells to proceed through the G2/M checkpoint can be a trigger for apoptosis. The induction of apoptosis by quercetin and tamoxifen was confirmed immunocytochemically by the in situ nick end labeling (TUNEL) reaction. These compounds also exerted a dose-dependent growth-inhibitory effect on primary tumor cells, as assessed by colony-forming assay and bromodeoxyuridine labeling. Laryngeal cancer cell lines and primary tumor cells expressed Type II estrogen binding sites (Type II EBS) with binding characteristics similar to those of Type II EBS in other tumor cells. Since the affinities of quercetin and tamoxifen for Type II EBS were correlated with their growth-inhibitory potential while ipriflavone neither interacted with these sites nor inhibited cell growth, the possibility exists that the action of these compounds is mediated, at least in part, by the interaction with Type II EBS. In conclusion, our data indicate that quercetin and tamoxifen could be potentially useful in laryngeal cancer treatment. Int. J. Cancer 77:747–754, 1998. © 1998 Wiley-Liss, Inc.

No abstract.