Microsatellite instability and loss of heterozygosity in squamous cell carcinoma of the head and neck.

BACKGROUND: Microsatellite instability (MSI) in head and neck squamous cell carcinoma (HNSCC) has been reported with a wide range of frequencies. The aim of our study was to disclose the frequency and basis of MSI in HNSCC and to correlate MSI and findings on loss of heterozygosity (LOH) with the clinical data. METHODS: We analyzed MSI and LOH in 91 tumors. All tumors presenting instability were analyzed for the expression of mismatch repair genes (MMR) proteins. RESULTS: Low-level microsatellite instability (MSI-L) was seen in 7.7% of the HNSCC. None of the MSI-L tumors had aberrant MMR protein expression. LOH rates up to 57% were identified for different regions on chromosome 3p. For the marker D10S197, we found a significant correlation between LOH and tumor stage IV. CONCLUSION: Our results indicate that MMR gene inactivation is rare among primary HNSCC. In contrast, the MSI-L phenotype plays a role in a small subset of tumors. LOH on chromosome arm 3p and 10p12 seems to be involved in tumorigenesis and progression HNSCC, respectively.

[Exploration of tumor suppressors p16INK4a and p14ARF in oral leukoplakias]. / Untersuchung der Tumorsuppressoren p16INK4a und p14ARF in Mundschleimhautleukoplakien.

The inactivation of p16 and p14ARF is considered to be an important step in the carcinogenesis of oropharygeal carcinomas. This consideration is supported by the observation of multiple allelic losses in the coding loci of chromosome 9p21 in squamous cell carcinomas and in dysplastic premalignant lesions. The present study hypothesized that comparable alterations already occur in leukoplakia, which are seen as potential predecessors of oral squamous cell carcinomas and that it is possible to differ leukoplakia with from leukoplakia without further malignant transformation. Furthermore we evaluated, whether such leukoplakia show sequence alterations in the genes p16 and p14ARF, which are capable to cause a limitation in gene function. The results show that the LOH pattern in genes p16 and p14ARF occur as well in leuplakia with malignant transformation as in leukoplakia, that do not show clinical alterations. The rate of allelic loss did not differ significantly. Overall, the incidence of allelic loss was lower in leuplakia compared to succeeding squamous-cell carcinomas (p<0,05). The results further illustrated an increase in LOH patterns in dyplastic leukoplakia, without reaching statistical significance. Significant increases in allelic losses were found in heavy smokers, (p < 0,05). PCR analysis of the exons 1-alpha, exon 1-beta and exon 2 in leukoplakia, containing LOH patterns did not show genetic alterations. Thus we concluded, that gene deletion and gene mutation have a minor role in the inactivation process of p16 and p14ARF in oral leukoplakia. Representing an early process in carcinogenesis, gene deletion and mutation occur in leukoplakia with and without malignant transformation. Therefore, taken as a singular parameter they represent an uncertain criteria to assess the potential of malignant transformation. However they could provide information in combination with other genetic factors like chromosomal methylation patterns and histology.

[Early loss of teeth after treatment for childhood leukemia]. / Frühzeitiger Zahnverlust nach Leukämiebehandlung im KindesalterFallbericht und Literaturübersicht.

BACKGROUND: Only few reports of effects of radiotherapy in childhood on the dental apparatus are available in the literature. The basis for early loss of teeth appears to be a reduction of the root surface area after radiation exposure. These effects in the periodontium are a consequence of combined radiochemotherapy usually applied for treatment of childhood neoplasia. Chemotherapy alone also results in changes of periodontal development. CASE REPORT: A 33-year-old patient is reported, who, at the age of 11 years, received high-dose chemotherapy and radiotherapy of neuroaxis and cranium for acute lymphatic leukemia with relapse. The patient consulted the Implant Section of the Department of Oral and Maxillofacial Surgery because of severe dental changes and tooth loss despite adequate dental care and oral hygiene. Radiation doses given to the superior maxilla and mandible at the age of 11 were estimated to be in the range of 8-25 Gy. CONCLUSION: Intense, life-long dental care and follow-up of patients cured from malignant disease in childhood must hence be postulated in order to minimize dental treatment sequelae by supportive measures, but also to initiate timely adequate dental and prosthetic management.

Loss of expression of ZAC/LOT1 in squamous cell carcinomas of head and neck.

BACKGROUND: ZAC/Lot1 is a previously identified candidate tumor suppressor gene. The gene maps to the human chromosome 6q24-q25, a region frequently deleted in squamous cell carcinomas of the head and neck and other solid tumors. METHODS: We have used a model of head and neck squamous cell carcinoma (HNSCC) and cell lines to analyze the role of the candidate tumor suppressor gene ZAC/Lot1 in oral carcinogenesis. We analyzed the expression in 11 cell lines, and we performed loss of heterozygosity (LOH)- and sequence analyses in 51 primary tumors. RESULTS: Three (27.3%) of 11 cell lines showed a distinctly reduced expression of ZAC/Lot1 compared with expression levels of the gene in the normal oral mucosa. In addition, we analyzed 51 primary squamous cell carcinomas of the head and neck for LOH with seven microsatellite markers flanking ZAC/Lot1. We detected an average LOH rate of 31.4% in the region of interest. Sequence analysis revealed no mutations for the ZAC/Lot1 coding exons, including the exon/intron boundaries. CONCLUSIONS: These data could suggest a minimal role for ZAC/Lot1 in a subgroup of HNSCC tumors.