Prognostic value of MMP-2, -9 and TIMP-1,-2 immunoreactive protein at the invasive front in advanced head and neck squamous cell carcinomas.

In head and neck cancer as well as in other carcinomas, tumor expansion and spread to distant sites require the secretion of destructive enzymes that degrade the extracellular matrix. A variety of proteases contribute to matrix destruction. Characteristics of the invasive tumor front may reflect tumor prognosis better than do other parts of the tumor. Therefore, it was the aim of the present study to (i) compare central and peripheral tumor zones for differences in the expression of matrix-metalloproteinases (MMP) -2 and -9 and their naturally occurring inhibitors (tissue inhibitor of matrix-metalloproteinases (TIMP) -1 and -2), (ii) examine the morphological potential of malignancy, and (iii) correlate these findings with clinicopathological parameters. The study population consisted of 106 surgical specimens of advanced head and neck squamous cell carcinomas. The invasive front was graded for malignancy, and immunohistochemical staining with MMP-2, MMP-9, TIMP-1 and TIMP-2 antibodies was performed. Both MMP-2 and MMP-9 were found to be significantly overexpressed at the tumor front. The MMP-2-positive invasive front exhibited diminished overall survival times. In multivariate analysis, MMP-2 expression retained its correlation with overall survival in addition to nodal status and total malignancy score. Expression of TIMP-2 correlated with local tumor invasion. We conclude that the expression of MMP-2 at the invasive front is a marker of poor survival and appears to be associated with early recurrence in initially lymph node-negative patients.

Reconstructive and rehabilitating methods in patients with dysphagia and nutritional disturbances.

As diverse as the causes of oropharyngeal dysphagia can be, as broad is the range of potential therapeutical approaches. In the past two decades, methods of plastic-reconstructive surgery, in particular microsurgically revascularised tissue transfer and minimally invasive, endoscopic techniques of every hue have substantially added to the portfolio of reconstructive surgery available for rehabilitating deglutition. Numerically, reconstructing the pharyngolaryngeal tract following resection of squamous-cell carcinomas in the oral cavity, the pharynx and the larynx has been gaining ground, as has functional deglutitive therapy performed to treat posttherapeutical sequelae. Dysphagia and malnutrition are closely interrelated. Every third patient hospitalised in Germany suffers from malnutrition; ENT tumour patients are not excluded. For patients presenting with advancing malnutrition, the mortality, the morbidity and the individual complication rate have all been observed to increase; also a longer duration of stay in hospital has been noted and a lesser individual toleration of treatment, diminished immunocompetence, impaired general physical and psychical condition and, thus, a less favourable prognosis on the whole. Therefore, in oncological patients, the dietotherapy will have to assume a key role in supportive treatment. It is just for patients, who are expected to go through a long process of deglutitive rehabilitation, that enteral nutrition through percutaneous endoscopically controlled gastrostomy (PEG) performed at an early stage can provide useful and efficient support to the therapeutic efforts. Nutrition and oncology are mutually influencing fields where, sooner or later, a change in paradigms will have to take place, i.e. gradually switching from therapy to prevention. While cancer causes malnutrition, feasible changes in feeding and nutrition-associated habits, including habitual drinking and smoking, might lower the incidence of cancer worldwide by 30 to 40% (American Institute of Cancer Research 1999).Esse oportet, ut vivas, non vivere ut edas. / Thou shouldst eat to live, not live to eat.Cicero 106 - 43 B.C.

Retention of the arginine allele in codon 72 of the p53 gene correlates with poor apoptosis in head and neck cancer.

The allele constitution at codon 72 of the p53 gene (CGC-arginine or CCC-proline) plays a major role in inducing apoptosis in p53 mutant cells. To verify this, we determined GC-status, p53-mutations, and p53-loss of heterozygosity (LOH) in a group of 54 squamous cell carcinomas of the head and neck (SCCHN). A novel approach, using a one-step real-time PCR analysis with fluorescent hybridization probes, was applied to detect the GC status in tumors and corresponding blood samples. p53 mutations in exons 4 to 8 were detected by PCR-SSCP-sequencing analysis. Apoptosis was determined immunohistochemically using antibodies against Fas, FasL, p53, Bcl2, and terminal deoxy-transferase-mediated dUTP nick end labeling (TUNEL) staining. The overall frequency of p53-LOH in SCCHN was 45.2%. In cases of LOH, there was a preferential loss of the proline allele, which was associated with an up-regulation of Bcl2 and lack of co-expression of Fas/FasL and, thus, impaired apoptosis (P < 0.001). Apoptosis was not observed in tumors carrying the arginine allele. p53 mutations were detected in 29.6% of SCCHN and preferentially occurred at the arginine allele (P = 0.01). p53 alterations were more frequently observed in tumors of the oral cavity, oropharynx and hypopharynx, whereas they were rare in larynx carcinomas (P = 0.07). The p53-LOH status was not found to be significantly correlated with sex, age, TNM-status, or tumor grading. We conclude that apoptosis is correlated with the allelic status of codon 72 in SCCHN. Homozygous proline 72 appears to be an important regulator of apoptosis via the Fas/FasL pathway in SCCHN.