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Potential biomarkers in predicting progression of epithelial hyperplastic lesions of the larynx.

Abstract
Factors contributing to malignant transformation of laryngeal pre-neoplastic lesions remain largely unknown. Potential etiologic factors may be related to a genetically controlled sensitivity to environmental carcinogens. In this study, we investigated bleomycin-induced chromosome fragility in 15 patients with laryngeal keratoses who experienced a malignant transformation of pre-neoplastic lesions during follow-up, as compared with chromosome fragility in 15 historical controls with no progression of laryngeal keratoses during a 10-year follow-up, in a match-paired analysis. Chromosomal analysis demonstrated a higher sensitivity to clastogens in patients with malignant progression of laryngeal pre-neoplastic lesions than that of control patients with no evolution of their original laryngeal keratoses (p < 0.01). Furthermore, in the attempt to identify possible prognostic markers we studied proliferative activity (MIB-1 expression) and p53 gene aberration in biopsy samples from non-invasive and invasive laryngeal lesions in both groups. p53 immunostaining was observed in 10/15 (66.7%) of pre-neoplastic lesions and in 11/15 (73.3%) of metachronous laryngeal cancers. No differences in terms of p53 expression were noted between transformed and not-transformed lesions. Mutations at p53 gene were observed in 3/15 (20%) of pre-invasive biopsies and in 4/5 (80%) of the laryngeal cancers analyzed. Our data suggest that p53 alteration is an early event in the genesis of a subset of laryngeal carcinomas and that there is no conclusive data about the possible clonal development of metachronous laryngeal carcinoma from a p53 mutated pre-invasive disease in the same patient. MIB-1 expression was found to progressively increase with degree of epithelial hyperplasia and dysplasia in both transformed (p = 0.007) and not-transformed (p < 0.1) lesions. Surprisingly, pre-invasive lesions with tumor evolution showed a lower proliferative activity when compared with laryngeal lesions without malignant transformation (p = 0.013). These data suggests that subjects with pre-neoplastic laryngeal lesion showing an increased susceptibility to carcinogens and with less proliferative disease could be at a higher risk for development of laryngeal carcinoma.
AuthorsO Gallo, A Franchi, I Chiarelli, B Porfirio, A Grande, L Simonetti, C Bocciolini, O Fini-Storchi
JournalActa oto-laryngologica. Supplementum (Acta Otolaryngol Suppl) Vol. 527 Pg. 30-8 ( 1997) ISSN: 0365-5237 [Print] NORWAY
PMID9197477 (Publication Type: Journal Article)
Chemical References
  • Antigens, Nuclear
  • Biomarkers
  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Nuclear Proteins
  • Bleomycin
Topics
  • Antigens, Nuclear
  • Biomarkers (analysis)
  • Biomarkers, Tumor (analysis)
  • Biopsy
  • Bleomycin (pharmacology)
  • Carcinoma, Squamous Cell (genetics, pathology)
  • Case-Control Studies
  • Cell Transformation, Neoplastic
  • Chromosome Fragility
  • Epithelium (pathology)
  • Female
  • Genes, p53
  • Humans
  • Hyperplasia
  • Immunohistochemistry
  • Ki-67 Antigen
  • Laryngeal Diseases (genetics, pathology)
  • Laryngeal Mucosa (pathology)
  • Laryngeal Neoplasms (genetics, pathology)
  • Male
  • Middle Aged
  • Mutation
  • Nuclear Proteins (analysis)
  • Precancerous Conditions (genetics, pathology)
  • Sequence Analysis, DNA

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