Loss of heterozygosity of tumor suppressor genes (p16, Rb, E-cadherin, p53) in hypopharynx squamous cell carcinoma.

OBJECTIVE: Microsatellite alterations, especially those that cause loss of heterozygosity (LOH), have recently been postulated as a novel mechanism of carcinogenesis and a useful prognostic factor in many kinds of malignant tumors. However, few studies have focused on a specific site, hypopharynx. The aim of this study was to evaluate the relationship between LOH and hypopharyngeal squamous cell carcinoma (HPSCC). STUDY DESIGN: Laboratory-based study. SETTING: Integrated health care system. SUBJECTS AND METHODS: Matched normal and cancerous tissues from 30 patients with HPSCC were examined for LOH in 4 tumor suppressor genes (TSGs) (p16, Rb, E-cadherin, and p53) at loci 9p21, 13q21, 6q22, and 17p13, respectively, using microsatellite markers amplified by polymerase chain reaction. The results for each loci were compared with clinicopathological features. RESULTS: Among the 30 cases, 26 (86.7%) exhibited LOH, with the most common alteration being LOH at p53 (52.6%). Significantly higher rates of LOH detection were seen in Rb, p53, and the LOH-high group (cases where 2 or more loci with LOH were found) in cases of lymph node metastasis. Compared with stage I and II carcinoma, tumors of stages III and IV had significantly higher frequencies of LOH in Rb, p53, and the LOH-high group. However, the presence of LOH was not significantly correlated with survival. CONCLUSION: These results suggest that LOH in TSGs such as Rb and p53 may contribute to the development and progression of HPSCC. The presence of LOH in the primary tumor may also be predictive of lymph node metastasis.

Loss of heterozygosity by mitotic recombination in diploid strain of Aspergillus nidulans in response to castor oil plant detergent.

Somatic recombination in heterozygous diploid cells may be a promotional agent of neoplasms by inducing homozygosity of defective genes. Tumor suppressor genes may in this way be completely suppressed in recombinant cells. In this work, the genotoxic effects of detergent derived from the castor oil plant (Ricinus communis) in heterozygous diploid cells of Aspergillus nidulans are evaluated. Previous studies have evaluated the application of this substance in endodontic treatments as an irrigating solution. The recombinogenic potential of the compound has been studied through the production of homozygous cells for nutritional markers riboA1, pabaA124, biA1, methA17, and pyroA4. Detergent was diluted to 1:10, 1:20, and 1:40, and morphologic alterations, delay in conidiophore development, and mitotic recombination occurrence were reported for the three dilutions. Although past studies have demonstrated the antimicrobial action of the detergent under analysis, our results revealed its cytotoxic effects and recombinogenic potential.

The molecular biology of laryngeal cancer.

Novel techniques have led to the discovery of many genes and gene products important in the development of HNSC and laryngeal cancer. Tumor suppressive genes and oncogenes have been identified, and many of their roles have been elucidated in a genetic progression model. As these molecular pathways become better understood, the information obtained will increasingly be used to guide patient therapy. Specifically, advances will probably be made in (1) molecular characterization of steps leading to laryngeal cancer; (2) molecular screening, staging, and surveillance; (3) molecularly based therapy, including gene transfer and small molecule therapy directed at specific molecular pathways involved in neoplasia; and (4) characterization of patients who are at high risk for laryngeal cancer. In the final analysis, however, smoking cessation for those at risk for head and neck cancer would have greater effect than all these efforts combined.

p53 alterations in betel quid- and tobacco-associated oral squamous cell carcinomas from Taiwan.

Alterations of p53 have been explored in Taiwanese oral squamous cell carcinomas (OSCCs) consisting of a betel quid (BQ)/tobacco-related subgroup of 36 subjects and a tobacco-related subgroup of 13 subjects. Mutations in conserved exons were found in 12 tumors. Seven mutations were clustered in a hot-spot region mapped to a region between codons 273-282 in exon 8. The incidence of p53 mutation in BQ/tobacco tumors was 22% (8/36). The frequency of p53 allelic loss (21%, 3/14) in BQ/tobacco tumors approximates to the incidence of mutation. This is the first study demonstrating allelic deletion of p53 in such malignancies. Twenty-four of 43 samples showed positive p53 immunostaining. All tumors harboring mis-sense mutations of p53 in conserved exons exhibited nuclear protein accumulation. The incidence of mutation in conserved exons in BQ/tobacco-associated Asian OSCCs (15%) is significantly different from worldwide OSCCs (46%) related primarily to tobacco consumption (P=0.00001).