Chromosomes 7,17 polysomies and overexpression of epidermal growth factor receptor and p53 protein in epithelial hyperplastic laryngeal lesions

Purpose: To visualize directly a sequence of genetic changes underlying the entire spectrum of epithelial hyperplastic laryngeal lesions (EHLL) and la ryngeal cancer by the use of non-isotopic in situ hybridization (ISH) for c hromosomes 7 and 17 in correlation with overexpression of p53 protein and e pidermal growth factor receptor (EGFR). The specific aim was to compare the results and prognostic significance between the two types of EHLL: isolate d, mainly atypical hyperplasia or risky epithelium, and EHLL associated wit h squamous cell carcinoma (SCC). Patients and Methods: 59 tissue specimens of EHLL obtained from 34 patients, graded according to the Ljubljana classi fication into simple (SH), abnormal (AbH) and atypical hyperplasia (AtH), a nd carcinoma in situ (CIS) were included in the study. Non-fluorescent ISH for chromosomes 7 and 17 was performed by biotinylated a-satellite DNA prob es. Immunohistochemical staining for EGFR and p53 protein was analyzed on t he same tissue samples. Results: Polysomy for both chromosomes increased in correlation with progressive grades of EHLL. The most important finding wa s the statistically significant difference in chromosome copy numbers betwe en the isolated AtH and AtH associated with SCC. Overexpression of EGFR and p53 protein was found in 61 (36/59) and 52% (31/59) of cases, respectively . The immunoreactivity for both markers increased with the grade of lesions , but the staining pattern was not so uniform in isolated EHLL. On the othe r hand, the immunoreactivity was expressed more constantly in EHLL adjacent to SCC. Conclusions: Numerical changes in chromosomes 7 and 17 might be as sociated with an upregulation of EGFR and p53 genes, and could contribute t o critical events in laryngeal carcinogenesis. For daily practice, the cyto genetic and immunohistochemical analyses could be of assistance in distingu ishing between low- and high-risk groups of AtH. However, the isolated form s of atypical hyperplasia need considerable further study by evaluating gen etic changes with the described methods regarding their ultimate transforma tion to carcinoma. Copyright (C) 2000 S. Karger AG. Basel