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[p53 as a biomarker in radiotherapy of carcinoma of the mouth cavity].

Multimodal therapy of oral squamous cell carcinomas today is based on surgery, radiotherapy and chemotherapy. Despite the combination of all three therapeutic options, there is still a large number of treatment failures and therefore major questions remain. Recent investigations suggest that mutations of the p53 tumor suppressor gene may account for some of the therapeutic failures. Inactivation of the gene may be an important determinant of the efficacy of today's multimodal therapy protocols. In 90 patients with squamous cell carcinomas of the oral cavity biopsy specimens were taken before and after preoperative radiochemotherapy. From all patients, biopsy and resection material was available for immunohistochemical analysis of p53. After radiation treatment, 51 patients (57%) showed a complete response; 39 patients (43%) only showed a partial response or did not respond at all. Among the responders, 82% of the pretherapeutic tumors were p53 positive, whereas among the nonresponders only 56% of the pretherapeutic tumors were p53 positive. The majority of the residual tumors were also p53 negative according to immunohistology after radiation treatment. In our study, detection of p53 protein by immunohistochemistry seemed to be connected with a more radiosensitive reaction of the tumors. Nevertheless, successful strategies for radiation therapy may need to take into account the tissue of origin and the status of p53 in the tumor.

Biomarkers, Tumor↗

[Cell kinetics of oral squamous epithelial carcinomas. Determination of the proliferation index and apoptosis rate with the TUNEL method].

Tumour growth is directly related to the multiplication of tumour cell numbers which can be caused, firstly, by increased proliferation and, secondly, by prolongation of the life span of tumour cells. The aim was the quantification of the increase and decrease (apoptosis) in cell numbers in relation to the cytological grading of oral squamous epithelial cell carcinoma. Proof of apoptosis-specific fragmentation of DNA (double-strand breaks) by the TUNEL method (TdT-mediated dUTP nick end labelling) and of proliferative activity by the monoclonal antibody MIB 1 was found in 41 oral squamous epithelial carcinomas of different grading. With progression of the cytological grading, an increase of proliferative activity and a decrease of apoptotic activity occurs. The apoptosis rates were 13.5% for G1 carcinomas, 8.5% for G2 carcinomas and 6.1% for G3 carcinomas. The results confirm that during progression to higher malignant cellular phenotypes of oral squamous carcinoma, increased proliferative activity as well as reduced apoptosis rates contribute substantially to the multiplication of tumour cell numbers and show that during progression a loss of control of programmed cell death (apoptosis) occurs. However, the high standard deviations of apoptosis rates within the different grades disprove an individual prognostic significance.

Apoptosis↗

[Early detection of multiple tumors in primary diagnosis of oral carcinomas using panendoscopy].

Early diagnosis of additional carcinomas in the diagnosis of primary oral squamous epithelial carcinomas is important for prognosis and provides helpful pointers for planning therapy. In a prospective study from 1993 to 1998, 83 patients with histologically confirmed primary squamous epithelial carcinomas of the oral cavity, the oropharynx and the lip underwent panendoscopy staging to check whether early diagnosis of simultaneous, additional carcinomas of the upper aerodigestive tract is possible with this method. Panendoscopy commenced with rigid tracheobronchoscopy followed by rigid esophagoscopy. Afterwards, the nasopharynx, oropharynx and hypopharynx were examined endoscopically. Finally, microlaryngoscopy was performed. Biopsy and microbiological smears were taken from suspect areas. The incidence of simultaneous, additional carcinomas was 8.4%. All tumors were located in the upper aerodigestive tract with the exception of the esophagus, trachea and bronchial system. A simultaneous laryngeal carcinoma was also diagnosed on the vocal cord in a patient with lip carcinoma. Precancerous conditions could also be diagnosed by means of panendoscopy. This study and two retrospective studies from 1988 to 1994 from the Clinic of Oromaxillofacial Surgery and from the Regensburg Tumor Center (1993 to 1997) confirm the high proportion of additional carcinomas in a primary cancer in the "head and neck region." The financial costs and instrumental requirements of the method appear to be justified in view of the high proportion of simultaneous, additional tumors. Expierience so far and the uncomplicated course indicate that this investigation does not entail any additional risk for the patient, which is why panendoscopy can be recommended without reservations for staging in tumors in the head and neck region.

Adult↗

[Clinical and histopathological characterization of oral leukoplakia in patients with HIV infection].

The aim of this study was to assess the prevalence of oral leukoplakia (OL) in HIV-positive patients and to evaluate the clinical and histopathological features and the presence of Candida hyphae and viral infections (HSV 1, 2, HPV, EBV and CMV) by immunocytochemical methods using mono- or polyclonal antibodies. A total of 269 HIV-seropositive patients, (222 men, median age 36.7 years and 47 women, median age 32 years) were registered. OL occurred in 20/269 (7.4%) patients (men, smokers, median age 38 years); the non-homogeneous form was observed in 11%. A lesional biopsy specimen was obtained from 8/20 patients. Specimens did not show signs of epithelial dysplasia. Candida hyphae were evident in 2/8 cases. Two patients tested positive for HPV and CMV; antibodies against EBV, HSV1 and 2 were negative. In conclusion, the prevalence of OL is comparatively high in this group of HIV-seropositive patients (7.4% vs. 0.9-2.2%). Moreover, the mean age of the study group at the time of diagnosis for OL was lower (38 years vs. 60 years).

AIDS-Related Opportunistic Infections↗

[Visualizing carcinomas of the mouth cavity by stimulating synthesis of fluorescent protoporphyrin IX].

The fluorescence diagnosis based on the aminolavulinic acid-stimulated porphyrin synthesis allows the detection of superficial tumors in a very early stage even when they are very small tumors. A fluorescence diagnosis of tumors in the oral cavity can be simply performed by rinsing with a 0.4% ALA solution for 20 min. This topical application avoids systemic side effects such as skin sensitization. The red fluorescent areas are visible to the naked eye; only a blue light source for fluorescence excitation is necessary and a suitable red filter for observation. In our study on 56 patients suffering from carcinoma of the oral cavity, 96% of the histologically confirmed carcinoma could be visualized via fluorescence. In 3 patients additional tumors were detected via fluorescence that were not visible otherwise. However, many patients show fluorescent areas with no correlation to the histological finding. It was verified that bacteria from the oral cavity also produce PpIX after ALA incubation, which leads to false-positive findings. Reduction of the false-positive findings was achieved by rinsing the oral cavity with hydrogen peroxide and by mechanical plaque reduction. This improves the reliability of a fluorescence-guided biopsy. However, suppression of the bacteria fluorescence is necessary for clinical use of this diagnostic method.

Adult↗

[Experimental chemotherapy of xenotransplanted oral squamous epithelial carcinoma: effectiveness of docetaxel (taxotere) in the nude mouse model].

Originating from plants, the taxoids, in particular docetaxel (Taxotere), represent progress in antitumoral chemotherapy. In addition to their use as palliative treatment they have also proved to be increasingly important for adjuvant and neoadjuvant treatment of oral squamous cell carcinoma (SCC). In the present nude mouse model the efficacy of chemotherapeutic agents against exemplary oral SCC were examined using cell line HNSCC 001. Typical biological properties such as expression of serum tumor markers and treatment-related alteration were reviewed. Intraperitoneal administration of 30 mg docetaxel per kilogram body weight at a time resulted in significant growth inhibition (P < 0.001), however without complete remission. Mean values of relative tumor volume ranged from 95% to 131% in the treated groups as compared to 311% in animals without treatment. Application more frequently than weekly did not result in a significant increase in antitumor activity. From the present experimental study no final conclusion can be drawn regarding weekly docetaxel administration mostly used in clinical phase II trials. Except for SCC, for which values correlated well with tumor volume (r = 0.85 without treatment and r = 0.87 with treatment), on the one hand, and a distinct treatment-related decrease, on the other, the tested tumor markers TPA and TPS proved to be less valuable for screening of treatment and follow-up in this murine model.

Aged↗

Growth of normal oral keratinocytes and squamous cell carcinoma cells in a novel protein-free defined medium.

A novel protein-free synthetic medium was developed for the culture of normal human oral keratinocytes. This medium, designated PFM-7, supports the serial cultivation of primary or secondary normal oral keratinocytes in protein-free, chemically defined conditions. Normal oral keratinocytes in PFM-7 exhibited nearly equal growth in mass culture without noticeable changes in morphology, response to added growth factors, or gene expression of growth factors and their receptors, compared to cells in Keratinocyte-SFM containing epidermal growth factor and bovine pituitary extract. Furthermore, PFM-7 supported the serial subcultivation of human squamous cell carcinoma cells and enabled both normal and malignant oral squamous cells derived from the same patient to grow under the same protein-free defined conditions. These results indicate that PFM-7 can be used for precise investigations of growth mechanisms, cell products, and gene expression associated with carcinogenesis of human epidermal cells.

Animals↗

Prognostic effect of tobacco and alcohol use in patients with oral tongue cancer.

A retrospective case analysis shows that patients with oral tongue cancer who have chronically used tobacco and alcohol have an increased incidence of death due to tumor, due to a second primary cancer, and due to intercurrent disease when compared with patients with oral tongue cancer who have never used tobacco or alcohol. This difference is not explained by a difference in tumor staging, patients' ages, or type of treatment received.

Alcohol Drinking↗

Premalignant changes in normal appearing epithelium in patients with squamous cell carcinoma of the upper aerodigestive tract.

Biopsy specimens of "normal" mucous membrane of patients susceptible to the effects of the carcinogens of tobacco revealed morphologic abnormalities on electron microscopic examination that were consistent with the concept that carcinogenesis is a multistep process of sequential neoplastic development extending over a long period of time. Such changes in the upper aerodigestive tract are probably tobacco induced and may be reversible if tobacco exposure is eliminated. Use of the electron microscope can provide the clinician with an accurate assay of the severity of mucosal alterations induced by tobacco. The ability to detect such morphologic abnormalities should provide another deterrant to smoking and a useful tool in the further study of these phenomena.

Adult↗

Oral lichen planus.

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Administration, Topical↗