Chromosomes 7,17 Polysomies and Overexpression of Epidermal Growth Factor Receptor and p53 Protein in Epithelial Hyperplastic Laryngeal Lesions

Abstract

Purpose: To visualize directly a sequence of genetic changes underlying the entire spectrum of epithelial hyperplastic laryngeal lesions (EHLL) and laryngeal cancer by the use of non-isotopic in situ hybridization (ISH) for chromosomes 7 and 17 in correlation with overexpression of p53 protein and epidermal growth factor receptor (EGFR). The specific aim was to compare the results and prognostic significance between the two types of EHLL: isolated, mainly atypical hyperplasia or risky epithelium, and EHLL associated with squamous cell carcinoma (SCC). Patients and Methods: 59 tissue specimens of EHLL obtained from 34 patients, graded according to the Ljubljana classification into simple (SH), abnormal (AbH) and atypical hyperplasia (AtH), and carcinoma in situ (CIS) were included in the study. Non-fluorescent ISH for chromosomes 7 and 17 was performed by biotinylated α-satellite DNA probes. Immunohistochemical staining for EGFR and p53 protein was analyzed on the same tissue samples. Results: Polysomy for both chromosomes increased in correlation with progressive grades of EHLL. The most important finding was the statistically significant difference in chromosome copy numbers between 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 other hand, the immunoreactivity was expressed more constantly in EHLL adjacent to SCC. Conclusions: Numerical changes in chromosomes 7 and 17 might be associated with an upregulation of EGFR and p53 genes, and could contribute to critical events in laryngeal carcinogenesis. For daily practice, the cytogenetic and immunohistochemical analyses could be of assistance in distinguishing between low- and high-risk groups of AtH. However, the isolated forms of atypical hyperplasia need considerable further study by evaluating genetic changes with the described methods regarding their ultimate transformation to carcinoma.

Simultaneous over activation of EGFR, telomerase (h TERT), and cyclin D1 correlates with advanced disease in larynx squamous cell carcinoma: a tissue microarray analysis

“…Aneusomy seems to characterize chromosomes 8, 9, 11, whereas chromosome 7 and 17 polysomy is a frequent event in these lesions and maybe modify EGFR and p53 protein expression levels, respectively [28,29]. In this study, chromosome 7 and also EGFR gene amplification was not strongly associated with EGFR protein expression levels.…”

Tissue microarray analysis of EGFR and HER2 oncogene copy number alterations in squamous cell carcinoma of the larynx

“…It has been shown that the overexpressed receptors correlate with more advanced tumors, poor survival, and higher risk of lymph node metastasis. (Rafferty et al 2001;Takes et al 2001;Ling et al 2000;Gale et al 2000;Watanabe et al 1999;Almadori et al 1999;Maurizi et al 1996).…”

The Supplementary Diagnostic Power of Selected Immunohistochemical, Molecular Genetic and Infective Parameters in Epithelial Hyperplastic Laryngeal Lesions

“…Although clinical data support the concept of this new classification [4], a critical approach raises the question, if other than the clearly defined histological criteria could distinguish the different stages of EHLL. In this context, first studies hint at a possible diagnostic importance of immunohistological and cytogenetic analyses for daily practice [2, 5]. This attracted us to search for further characteristics of different laryngeal hyperplastic stages, paying special attention to the crucial step between benign and risky epithelium defined by the Ljubljana classification.…”