These results hint at differences in the etiology of two distinct histological entities of head and neck cancer. Further research in this field could complete these preliminary data and provide the background for specific preventive strategies.

Although the number of investigated BSCCs is rather low and did not allow statistical conclusions, our results focus on certain differences between the molecular pathogenesis of BSCCs and SCCs.

Infection with human papillomavirus (HPV) and alterations in certain genes have frequently been proposed as mechanisms in the pathogenesis of head and neck squamous cell carcinoma (HNSCC). Here, we investigated 47 HNSCC for the presence of HPV and, by fluorescence in situ hybridisation, for amplification of Int-2 and Hst-1 in the search for a possible correlation. The highest frequency of HPV infection was found in hypopharyngeal carcinomas, while amplification of Int-2 or Hst-1 was distributed more equally among the different localisations. Amplification of Int-2 was detectable (7 of 9 cases) in 78% of the HPV-positive carcinomas, whereas no virus infection could be found in the five cases with amplified Hst-1 only. In spite of the rather low number of infected tumour samples, our results suggest a correlation between HPV infection and amplification of Int-2.

Objectives: MIB-1 and p53 protein expression, loss of heterozygosity (LOH), microsatellite instability (MSI) of di- and mononucleotide repeats, and HPV status were tested for their potential to characterize different stages of epithelial hyperplastic laryngeal lesions (EHLL). Methods: Thirty-two EHLL were reclassified according to the Ljubljana classification into simple (SH), abnormal (AbH), atypical hyperplasia (AtH) and carcinoma in situ, and investigated by immunohistochemical methods, PCR and direct sequencing analysis. Results: MIB-1 increased with progressive grades of EHLL, whereas p53 protein expression was distinctive only between SH and AbH. LOH showed increasing frequency with grades of the lesions, but the distribution of altered loci (9p, 9q, 10q, 11q, 17p) was not qualified to differentiate between the stages. MSI was detected in SH, AbH and AtH without clear correlation to histopathological grading. HPV infection occurred mostly in SH and AbH (both: 66.7%). Conclusion: MIB-1 labeling and allelic loss could assist histopathological diagnosis in the entire spectrum of EHLL, whereas the MSI results point to a genetic instability of the laryngeal mucosa in general and are therefore not helpful in the distinction of different stages of EHLL. However, future molecular genetic analyses should consider more late events of laryngeal carcinogenesis to improve their diagnostic potential. Furthermore, our results indicate that nonrisky and risky EHLL could probably be caused by different exogenous factors.

The authors describe a clear cell chondrosarcoma of the larynx. The clear cell type is a rare variant of chondrosarcoma that only twice has been reported in this localization. The light-microscopic diagnosis of the actual case was confirmed by immunohistochemical results, in particular by positive staining for S-100 protein and collagen type II, and ultrastructural findings. Loss of heterozygosity analysis demonstrated allelic loss at 9p22 and 18q21, but neither in the region of the Rb gene on chromosome 13q nor at the p53 locus on chromosome 17p where allelic loss has already been reported in chondrosarcomas. Furthermore, our molecular genetic investigations revealed a methylation of the cell cycle control gene p16, which is localized on chromosome 9p. This characteristic has been recorded previously only in high-grade chondrosarcomas. Mutations in the exons of p16, alterations of the putative tumor suppressor gene MMAC1/PTEN on chromosome 10q, or an amplification of the cyclin D1 gene (CCND1) on 11q13, which were found to be changed in other studies of chondrosarcomas, could not be demonstrated here.

Few biochemical analyses on the mixed salivary kallikrein-prokallikrein system exist. At present, there is no statistically relevant information about possible relationships between mixed salivary kallikreins and malignant processes, especially oral squamous cell carcinoma. In order to prove quantitative alterations of the kallikrein-prokallikrein system in the presence of oral squamous cell carcinoma, we estimated the enzyme content in mixed saliva from 15 men with oral squamous cell carcinoma and proenzyme in 14 men with the same tumors. Seventeen males served as controls for enzyme and 16 for proenzyme. Enzymatic cleavage of the chromogenetic tripeptide DL-Val-Leu-Arg-p-nitranilide was used. Additionally, we investigated a control group of 17 women of the same age as the males in order to record normal enzyme and proenzyme levels. The Mann-Whitney-Wilcoxon test showed highly significant elevation of mixed saliva kallikrein (P = 0.0003) and a highly significant increase in prokallikrein (P = 0.0012) in patients with the oral squamous cell carcinomas. The present findings indicate a probable biochemical role of the mixed saliva kallikrein and prokallikrein in the pathogenesis of oral tumors.

Relevant prognostic factors for head and neck squamous cell carcinoma are tumor extension (pT), occurrence of lymph node metastases (pN) and grade of differentiation (G). We tried to correlate these histological characteristics with numerical aberrations of whole chromosomes as demonstrated by fluorescence in situ hybridization techniques (FISH). Therefore, we investigated isolated interphase cells from paraffin sections of squamous cell carcinomas of the head and neck region from 46 patients with centromeric DNA probes for chromosomes 1, 3, 4, 6, 7, 9, 10, 11, 12, 15, 17, 18, X and Y. The majority of tumor samples showed aneuploidy for most chromosomes analyzed. The main chromosomal abnormality was loss of chromosomal material, predominantly of chromosomes 3 (28%), 6 (20%), 9 (26%), 10 (24%) and 18 (33%). Multiple deletions could be demonstrated more frequently in poorly differentiated carcinomas (88% G3-tumors with more than one deletion in contrast to 66% G2-tumors). The occurrence of multiple deletions may also correlate with progression in lymph node metastasis (66% in pN0-tumors vs. 85% in pN2-tumors), whereas the differences between the stages of primary tumor extension were not so obvious. Despite of a some-what disproportionate distribution of tumors in the different pT- and pN-stages and the rather low number of cases, our results suggest a relationship between the quantity of chromosomal underrepresentation, grade of differentiation and higher lymph node stage. Therefore, they underline the importance of chromosomal deletions as a possible additional prognostic marker in head and neck squamous cell carcinoma.