title: 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.
authors.affiliation: Institute of Otolaryngology-Head & Neck Surgery, University of Florence, Italy.
authors.forename: O
authors.initials: O
authors.lastname: Gallo
authors.forename: A
authors.initials: A
authors.lastname: Franchi
authors.forename: I
authors.initials: I
authors.lastname: Chiarelli
authors.forename: B
authors.initials: B
authors.lastname: Porfirio
authors.forename: A
authors.initials: A
authors.lastname: Grande
authors.forename: L
authors.initials: L
authors.lastname: Simonetti
authors.forename: C
authors.initials: C
authors.lastname: Bocciolini
authors.forename: O
authors.initials: O
authors.lastname: Fini-Storchi
mesh_terms: D034961:Antigens, Nuclear; D015415:Biomarkers / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D001761:Bleomycin / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic; D002873:Chromosome Fragility; D004848:Epithelium / Q000473:pathology; D005260:Female; D016158:Genes, p53; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D007818:Laryngeal Diseases / Q000235:genetics / Q000473:pathology*; D007820:Laryngeal Mucosa / Q000473:pathology*; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000032:analysis; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology*; D017422:Sequence Analysis, DNA
chemical_list: D034961:Antigens, Nuclear; D015415:Biomarkers; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D001761:Bleomycin